1,066 results
Search Results
2. ELECTRICALLY CONDUCTIVE FIBRE COMPOSITES PREPARED FROM POLYPYRROLE-ENGINEERED PULP FIBRES.
- Author
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Bin Huang, Guojun Kang, and Yonghao Ni
- Subjects
FIBERS ,ELECTRIC conductivity ,PERCOLATION ,PAPER ,POLYMERS ,CHEMICAL engineering - Abstract
Copyright of Canadian Journal of Chemical Engineering is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2005
3. Live fast– live long? A commentary on a recent paper by Speakmanet al.
- Author
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Van Voorhies, Wayne A.
- Subjects
- *
AGING , *DEVELOPMENTAL biology , *GERONTOLOGY , *LONGEVITY , *RESEARCH , *METABOLISM , *REACTIVE oxygen species - Abstract
Comments on a research paper about aging. Correlation between metabolic rate and longevity; Scientific origin of the concept of aging; Factors involved to determine the rate of reactive oxygen species.
- Published
- 2004
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4. Heart Failure Association/European Society of Cardiology position paper on frailty in patients with heart failure.
- Author
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Vitale, Cristiana, Jankowska, Ewa, Hill, Loreena, Piepoli, Massimo, Doehner, Wolfram, Anker, Stefan D., Lainscak, Mitja, Jaarsma, Tiny, Ponikowski, Piotr, Rosano, Giuseppe M.C., Seferovic, Petar, and Coats, Andrew J.
- Subjects
HEART failure patients ,MEDICAL personnel ,DISEASE complications ,CARDIOLOGY - Abstract
Heart failure (HF) and frailty are two distinct yet commonly associated conditions. The interplay between the two conditions is complex, due to overlaps in underlying mechanisms, symptoms and prognosis. The assessment of frailty in patients with HF is crucial, as it is associated with both unfavourable outcomes and reduced access and tolerance to treatments. However, to date a consensus definition of frailty in patients with HF remains lacking and the need for a validated assessment score, for identifying those HF patients with frailty, is high and timely. This position paper proposes a new definition of frailty for use by healthcare professionals in the setting of HF and creates a foundation for the design of a tailored and validated score for this common condition. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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- View/download PDF
5. Pressure injury education for older adults and carers living in community settings: A scoping review.
- Author
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Sahay, Ashlyn, Willis, Eileen, and Yu, Stephen
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PAMPHLETS ,HEALTH literacy ,REINFORCEMENT (Psychology) ,INDEPENDENT living ,COGNITIVE testing ,CONVERSATION ,CINAHL database ,TEACHING aids ,PRIMARY health care ,CULTURE ,PROFESSIONAL peer review ,BEHAVIOR ,CAREGIVERS ,SYSTEMATIC reviews ,MEDLINE ,LITERATURE reviews ,AGING ,MEDICAL databases ,PATIENT-professional relations ,LITERACY ,CONTINUING education ,SOCIAL support ,PRESSURE ulcers ,DIET ,PHYSICAL mobility ,DISEASE risk factors - Abstract
Older adults are at increased risk of pressure injuries (PIs) due to age‐related changes. Traditionally, PI knowledge and education have been delivered in hospitals and residential aged care facilities, however, there remains a critical gap in understanding how PI knowledge on prevention and management is shared with older adults and their carers living in the community. We aimed to describe the nature and characteristics of structured and unstructured PI education programs available to community‐dwelling older adults and their carers. As coping review was undertaken. We searched five databases: CINAHL, Medline, Scopus, Cochrane Library and ProQuest from 2009 to August 2023. The review was guided by Arksey and O'Malley's six‐step framework and adhered to the PRISMA‐ScR guidelines. It included primary peer‐reviewed papers published in English, which focus on PI education for older adults and/or their carers living in community settings. Data extraction was organised in a table, and findings presented as a narrative summary. One‐hundred and thirty‐six papers were screened and four included in the review. Results indicate that consideration was placed on literacy levels and cognitive status of older adults and their carers when designing PI education materials. Educational materials such as leaflets/brochures, in‐person training sessions or a combination of both were used. However, duration of these interventions varied, lasting for 1–4 weeks while others were completed over 12 months. Some improvements in PI knowledge such as how to treat PI, dietary requirements and importance of mobility were noted. However, information retention and its translation into effective long‐term behaviour change remained unclear. In conclusion, adopting a multifaceted educational approach increases the effectiveness of PI knowledge translation. Continuous education, support and reinforcement on PIs over time are necessary when interacting with older adults and caregivers to ensure long‐term management and prevention success. Conversations on PIs should start at the primary care levels when older adults and carers are visiting their GP clinics and accessing support services for other healthcare needs. Understanding older adults' and carers' literacy levels, cognitive status and cultural background can assist clinicians in designing and delivering fit‐for‐purpose PI educational interventions that are accessible, relatable and effective in promoting knowledge transfer and behaviour change. Carers are vital conduits in the care continuum. These factors will lead to a more informed, collaborative and person‐centred approaches to PI management and prevention. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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6. The cellular bases of mobility from the Study of Muscle, Mobility and Aging (SOMMA).
- Author
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Cummings, Steven R., Coen, Paul M., and Ferrucci, Luigi
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MOBILITY of older people ,AGING ,CELLULAR aging ,CARDIOPULMONARY fitness ,OLDER people ,WALKING speed ,POST-translational modification - Abstract
Findings from the Study of Muscle, Mobility and Aging (SOMMA) in this issue of Aging Cell show that several biological pathways in skeletal muscle cells play an important role in determining mobility in older adults. These are based on assays in skeletal muscle biopsies obtained from participants, aged 70 years and older in SOMMA tested for association with assessments related to mobility, including muscle mass, strength, power, cardiopulmonary fitness, and 400 m walking speed. The papers show that, using mass spectrometry, oxidative modifications of proteins essential to myocellular function are associated with poorer mobility. Using RNA‐seq to quantify gene expression, lower levels of expression of antioxidant enzymes located in mitochondria, autophagy, patterns of expression of genes involved in autophagy, and higher levels of RNA transcripts that increase with denervation were associated with poorer performance on tests of mobility. These results extend previous research from the Baltimore Longitudinal Study of Aging and recent studies from SOMMA showing the importance of mitochondrial energetics in mobility. Together, these findings are painting a picture of how fundamental cellular processes influence the loss of mobility with aging. They may also be a window on aging in other cells, tissues, and systems. The data collected in SOMMA are publicly available and SOMMA welcomes collaborations with scientists who are interested in research about human aging. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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7. Advances in the study of the glymphatic system and aging.
- Author
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Xiong Y, Yu Q, Zhi H, Peng H, Xie M, Li R, Li K, Ma Y, and Sun P
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- Humans, Animals, Astrocytes metabolism, Brain metabolism, Aquaporin 4 metabolism, Glymphatic System physiology, Glymphatic System metabolism, Aging physiology, Aging metabolism
- Abstract
The glymphatic system is cerebrospinal fluid-brain tissue fluid exchange flow mediated by aquaporin-4 (AQP4) on the end feet of astrocytes for a system, which is capable of rapidly removing brain metabolites and thus maintaining brain homeostasis, and is known as the central immune system. Dysfunction of the glymphatic system causes accumulation of misfolded and highly phosphorylated proteins (amyloid-β and Tau proteins), which destabilizes the proteins, and the body's neuroinflammatory factors are altered causing aging of the immune system and leading to neurodegenerative diseases. Damage to the glymphatic system and aging share common manifestations, as well as unstudied biological mechanisms that are also linked, such as mitochondria, oxidative stress, chronic inflammation, and sleep. In this paper, we first summarize the structure, function, and research methods of the glymphatic system and the relationship between the glymphatic system and the peripheral immune system, and second, sort out and summarize the factors of the glymphatic system in removing metabolites and resolving aging-related diseases and factors affecting aging, to explore its related biological mechanisms, and moreover, to provide a new way of thinking for treating or intervening aging-related diseases., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)
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- 2024
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8. Interactions between mitochondrial dysfunction and other hallmarks of aging: Paving a path toward interventions that promote healthy old age.
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Li, Yuan, Berliocchi, Laura, Li, Zhiquan, and Rasmussen, Lene Juel
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OLD age ,AGING ,MITOCHONDRIA ,PAVEMENTS ,RESEARCH personnel ,HUMAN experimentation - Abstract
Current research on human aging has largely been guided by the milestone paper "hallmarks of aging," which were first proposed in the seminal 2013 paper by Lopez‐Otin et al. Most studies have focused on one aging hallmark at a time, asking whether the underlying molecular perturbations are sufficient to drive the aging process and its associated phenotypes. More recently, researchers have begun to investigate whether aging phenotypes are driven by concurrent perturbations in molecular pathways linked to not one but to multiple hallmarks of aging and whether they present different patterns in organs and systems over time. Indeed, preliminary results suggest that more complex interactions between aging hallmarks must be considered and addressed, if we are to develop interventions that successfully promote healthy aging and/or delay aging‐associated dysfunction and diseases. Here, we summarize some of the latest work and views on the interplay between hallmarks of aging, with a specific focus on mitochondrial dysfunction. Indeed, this represents a significant example of the complex crosstalk between hallmarks of aging and of the effects that an intervention targeted to a specific hallmark may have on the others. A better knowledge of these interconnections, of their cause‐effect relationships, of their spatial and temporal sequence, will be very beneficial for the whole aging research field and for the identification of effective interventions in promoting healthy old age. [ABSTRACT FROM AUTHOR]
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- 2024
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9. A Community of Practice to increase education and collaboration in dementia and ageing research and care: The Liverpool Dementia & Ageing Research Forum.
- Author
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Giebel, Clarissa, Tetlow, Hilary, Faulkner, Thomas, and Eley, Ruth
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TREATMENT of dementia ,RESEARCH methodology ,CONFERENCES & conventions ,COMMUNITIES of practice ,AGING ,DEMENTIA ,INTERPROFESSIONAL relations ,WEBINARS ,DESCRIPTIVE statistics ,DATA analysis software ,DEMOGRAPHY ,MEDICAL research - Abstract
Background: Too often, dementia research is conducted in research silos without thorough integration and the involvement of people with lived experiences, care professionals and the Third Sector. Research can also get lost in academic publications, without reaching those benefiting most from the evidence. The aim of this methods and evaluation paper was to outline the aims, components and evaluation of the public‐facing and ‐engaging Liverpool Dementia & Ageing Research Forum, to provide a blueprint for setting up similar communities of practice. Methods: The Forum was set up in 2019 with the aim to (a) connect different stakeholders in dementia and ageing and co‐produce research and to (b) inform and educate. This paper provides an account of the Forum model and evaluates the following key elements: (1) engagement; (2) experiences of the Forum and its impact (via an online evaluation survey and three reflections). All Forum members and attendees were asked to complete a brief evaluation survey about their experiences from October to November 2022. Three regular Forum attendees provided a case study about their involvement and its impact. Findings: The Forum has reached out to diverse stakeholders and the general public, generating growing interest and engagement since its initiation. Forty‐four members and attendees completed the survey. Most attendees completing the evaluation survey have so far engaged in between 5 and 20 activities (47.8%), and 91% felt the aims of the Forum have been met. Engaging in the Forum has produced various benefits for attendees, including increased research capacity and knowledge, as well as improved connectivity with other stakeholders. Eleven percent of respondents, 39% of lived experts, stated they experienced improved access to postdiagnostic care. Conclusions: This is the first reported multistakeholder Community of Practice (CoP) on dementia and ageing. We make key recommendations for setting up and running similar dementia CoP, as they provide a noninterventional format for raising awareness, capacity and access to dementia care. Patient and Public Involvement: This paper reports on the involvement and engagement of people with dementia, unpaid carers, health and social care providers and Third Sector organisations in a CoP. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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10. Antioxidant potential of chlorogenic acid in Age‐Related eye diseases.
- Author
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Tang, Yu, Fang, Chi, Shi, Jian, Chen, Huimei, Chen, Xiong, and Yao, Xiaolei
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CHLOROGENIC acid ,EYE diseases ,MACULAR degeneration ,OXIDATIVE stress ,DIABETIC retinopathy ,OPHTHALMIC drugs - Abstract
Oxidative stress is an important mechanism of aging, and in turn, aging can also aggravate oxidative stress, which leads to a vicious cycle. In the process of the brain converting light into visual signals, the eye is stimulated by harmful blue‐light radiation directly. Thus, the eye is especially vulnerable to oxidative stress and becomes one of the organs most seriously involved during the aging process. Cataracts, age‐related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), and dry eye are inextricably linked to the aging process and oxidative stress. Chlorogenic acid (CGA) has been demonstrated to have antioxidant and anti‐inflammatory activities, and its validity has been established experimentally in numerous fields, including cardiovascular disease, metabolic disorders, cancers, and other chronic diseases. There has previously been evidence of CGA's therapeutic effect in the field of ophthalmopathy. Considering that many ophthalmic drugs lead to systemic side effects, CGA may act as a natural exogenous antioxidant for patients to take regularly, controlling their condition while minimizing side effects. In this paper, in vitro and in vivo studies of CGA in the treatment of age‐related eye diseases are reviewed, and the prospects of CGA's antioxidant application for the eye are discussed. The aim of this review is to summarize the relevant knowledge and provide theoretical support for future research. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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11. Older adults' needs and preferences for a nutrition education digital health solution: A participatory design study.
- Author
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Turner, Ashlee, Flood, Victoria M., and LaMonica, Haley M.
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HEALTH education ,PILOT projects ,PATIENT participation ,MEDICAL care for older people ,FOOD consumption ,DIGITAL health ,SMARTPHONES ,NUTRITION education ,QUALITATIVE research ,PATIENTS' attitudes ,EXPERIENCE ,COMPARATIVE studies ,QUESTIONNAIRES ,AGING ,COST effectiveness ,DESCRIPTIVE statistics ,NEEDS assessment ,THEMATIC analysis ,TECHNOLOGY ,DATA analysis software ,HEALTH promotion ,DIETARY patterns ,ADULT education workshops ,WORLD Wide Web ,OLD age - Abstract
Background: The global population is ageing rapidly and there is a need for strategies to promote health and wellbeing among older adults. Nutrition knowledge is a key predictor of dietary intake; therefore, effective educational programmes are urgently required to rectify poor dietary patterns. Digital health technologies provide a viable option for delivering nutrition education that is cost‐effective and widely accessible. However, few technologies have been developed to meet the unique needs and preferences of older adults. Objective: The aim of this study was to explore technology use among older adults and qualitatively determine the content needs and design preferences for an online nutrition education resource tailored to older adult consumers in Australia. Methods: Twenty adult participants aged 55 years and older (95% female) participated in one of four 2‐h participatory design workshops. In each workshop, prompted discussion questions were used to explore participants' technology use and preferences and to explore content needs and design preferences for an online nutrition education resource specific to older adults. Results: All participants were regularly using a range of different devices (e.g., smartphones, tablets and computers) and reported being comfortable doing so. Participants wanted a website that provided general nutrition information, practical advice and recipes. To enhance engagement, they sought a personalised resource that could be adjusted to suit their needs, included up‐to‐date information and allowed for easy sharing with others by exporting information as a PDF. Conclusions: Participatory design methods generate new knowledge for designing and tailoring digital health technologies to be appropriate and useful for the target audience. Specifically, older adults seek an online resource that has large and simple fonts with clear categories, providing them with practical advice and general nutrition information that can be personalised to suit their own needs and health concerns, with the option to export and print information into a paper‐based format. Patient or Public Contribution: Older adults actively participated in the development and evaluation process to generate ideas about potential features, functionalities, uses and practicalities of an online nutrition education resource. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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12. Who cares for the carer? Codesigning a carer health and wellbeing clinic for older care partners of older people in Australia.
- Author
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Layton, Natasha, Lalor, Aislinn, Slatyer, Susan, Lee, Den‐Ching A, Bryant, Christina, Watson, Moira, Khushu, Anjali, Burton, Elissa, Oliveira, Déborah, Brusco, Natasha L., Jacinto, Alessandro, Tiller, Elizabeth, and Hill, Keith D.
- Subjects
CAREGIVER attitudes ,EXPERIMENTAL design ,MEETINGS ,SOCIAL support ,FOCUS groups ,ATTITUDES of medical personnel ,ATTITUDE (Psychology) ,TELEPHONES ,MEDICAL care ,EXECUTIVES ,HEALTH status indicators ,VIDEOCONFERENCING ,CLINICS ,INTERVIEWING ,LANGUAGE & languages ,QUALITATIVE research ,EXPERIENCE ,SURVEYS ,TREATMENT effectiveness ,INTERPROFESSIONAL relations ,PSYCHOLOGY of caregivers ,HEALTH ,AGING ,RESEARCH funding ,NEEDS assessment ,JUDGMENT sampling ,POLICY sciences ,DATA analysis software ,ADULT education workshops ,EMAIL - Abstract
Introduction: Older carers or 'care partners' of older people experiencing care needs often provide essential support, at times while neglecting their own health and well‐being. This is an increasingly frequent scenario due to both demographic changes and policy shifts towards ageing in place. Multiple community stakeholders within the care and support ecosystem hold valuable expertise about the needs of older care partners, and the programme and policy responses that may better support their health and well‐being. The aim of this study was to identify the perspectives of stakeholders obtained through the codesign phase of a multicomponent research project investigating new models of care and support for older care partners suitable for the Australian context. Methods: Principles of codesign were used to engage a purposeful sample of older care partners, health professionals, researchers, policy makers and health service administrators. Participants took part in a series of three codesign workshops conducted remotely via video conferencing. The workshops were supported with briefing material and generated consensus‐based summaries, arriving at a preferred service model. Findings: This paper reports the research design and structure of the codesign panels, the range of findings identified as important to support the health and well‐being of older carers of older people, and the resulting service model principles. The codesigned and preferred model of care is currently being prepared for implementation and evaluation in Australia. Public Contribution: This study was conducted using codesign methodology, whereby stakeholders including older care partners and others involved in supporting older carers, were integrally involved with design, development, results and conclusions. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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13. Aging Cell Prize for Best Paper 2012.
- Author
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Adams, Peter, Antebi, Adam, Cuervo, Ana Maria, Kennedy, Brian, and Sedivy, John
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- *
EDITORIAL boards , *CELLULAR aging , *AGING , *HEAT shock proteins - Published
- 2013
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14. Autophagic receptor p62 protects against glycation-derived toxicity and enhances viability
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Malene Hansen, Carol Renneburg, Masaaki Komatsu, Jonathan Volkin, Sarah G Francisco, Paula Daza, Gemma Aragonès, Michael Workman, Allen Taylor, Opeoluwa Olukorede, Jose A. Rodriguez-Navarro, Helena Dominguez-Martín, Michael A. Brownlee, Caroline Kumsta, Wenxin Yang, Shun Kageyama, Xue Liang Du, Diego Ruano, Kalavathi Dasuri, Sheldon Rowan, Eloy Bejarano, Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular, Universidad de Sevilla. Departamento de Biología Celular, UCH. Departamento de Ciencias Biomédicas, Producción Científica UCH 2020, National Institutes of Health (US), National Institute of Food and Agriculture (US), Edward N. and Della L. Thome Memorial Foundation, BrightFocus Foundation, Ministerio de Economía y Competitividad (España), Human Nutrition Research Center on Aging (US), and Department of Agriculture (US)
- Subjects
Glycation End Products, Advanced ,0301 basic medicine ,Proteínas - Aspectos bioquímicos ,Aging ,Cell Survival ,Proteolysis ,Biology ,Pharmacology ,Kidney ,Proteotoxicity ,Cell Line ,Mice ,03 medical and health sciences ,Cells - Aging ,Proteins - Biochemical aspects ,0302 clinical medicine ,In vivo ,Glycation ,Lens, Crystalline ,medicine ,Autophagy ,Animals ,Humans ,Receptor ,Células - Envejecimiento ,P-glycoprotein ,Mice, Knockout ,Original Paper ,Retinal pigment epithelium ,medicine.diagnostic_test ,p62 ,RNA-Binding Proteins ,Epithelial Cells ,Original Articles ,Cell Biology ,Glicoproteína P ,Glycative stress ,Rats ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Toxicity ,Molecular biology ,Biología molecular ,Lysosomes ,030217 neurology & neurosurgery - Abstract
Diabetes and metabolic syndrome are associated with the typical American high glycemia diet and result in accumulation of high levels of advanced glycation end products (AGEs), particularly upon aging. AGEs form when sugars or their metabolites react with proteins. Associated with a myriad of age‐related diseases, AGEs accumulate in many tissues and are cytotoxic. To date, efforts to limit glycation pharmacologically have failed in human trials. Thus, it is crucial to identify systems that remove AGEs, but such research is scanty. Here, we determined if and how AGEs might be cleared by autophagy. Our in vivo mouse and C. elegans models, in which we altered proteolysis or glycative burden, as well as experiments in five types of cells, revealed more than six criteria indicating that p62‐dependent autophagy is a conserved pathway that plays a critical role in the removal of AGEs. Activation of autophagic removal of AGEs requires p62, and blocking this pathway results in accumulation of AGEs and compromised viability. Deficiency of p62 accelerates accumulation of AGEs in soluble and insoluble fractions. p62 itself is subject to glycative inactivation and accumulates as high mass species. Accumulation of p62 in retinal pigment epithelium is reversed by switching to a lower glycemia diet. Since diminution of glycative damage is associated with reduced risk for age‐related diseases, including age‐related macular degeneration, cardiovascular disease, diabetes, Alzheimer's, and Parkinson's, discovery of methods to limit AGEs or enhance p62‐dependent autophagy offers novel potential therapeutic targets to treat AGEs‐related pathologies., AGEs are toxic compounds formed by non‐enzymatic reactions between sugars and proteins. AGEs are prone to aggregate. Insoluble AGEs are efficiently removed via p62‐selective autophagy. The autophagic removal of AGEs is a conserved pathway, and the lack of p62 leads to accumulation of toxic AGEs in mouse and worms. Enhanced autophagy is protective against glycation‐derived damage. p62‐dependent autophagy offers novel potential therapeutic targets to treat AGEs‐related pathologies.
- Published
- 2020
15. Circumventing senescence is associated with stem cell properties and metformin sensitivity
- Author
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Xavier Deschênes-Simard, Marie Camille Rowell, Karine Moineau-Vallée, Benjamin Le Calvé, Nabeel Bardeesy, Sebastian Igelmann, Filippos Kottakis, Maxime Parisotto, Gerardo Ferbeyre, Paloma Kalegari, Emmanuelle Saint-Germain, and Véronique Bourdeau
- Subjects
0301 basic medicine ,Senescence ,Aging ,endocrine system diseases ,Context (language use) ,Mitochondrion ,Mice ,Structure-Activity Relationship ,03 medical and health sciences ,0302 clinical medicine ,Tumor Cells, Cultured ,Animals ,Humans ,STAT3 ,Cellular Senescence ,Original Paper ,Dose-Response Relationship, Drug ,biology ,Oncogene ,Stem Cells ,Cell Differentiation ,Cell Biology ,Original Papers ,Metformin ,3. Good health ,Telomere ,030104 developmental biology ,biology.protein ,Cancer research ,Signal transduction ,Stem cell ,030217 neurology & neurosurgery - Abstract
Most cancers arise in old individuals, which also accumulate senescent cells. Cellular senescence can be experimentally induced by expression of oncogenes or telomere shortening during serial passage in culture. In vivo, precursor lesions of several cancer types accumulate senescent cells, which are thought to represent a barrier to malignant progression and a response to the aberrant activation of growth signaling pathways by oncogenes (oncogene toxicity). Here, we sought to define gene expression changes associated with cells that bypass senescence induced by oncogenic RAS. In the context of pancreatic ductal adenocarcinoma (PDAC), oncogenic KRAS induces benign pancreatic intraepithelial neoplasias (PanINs), which exhibit features of oncogene‐induced senescence. We found that the bypass of senescence in PanINs leads to malignant PDAC cells characterized by gene signatures of epithelial‐mesenchymal transition, stem cells, and mitochondria. Stem cell properties were similarly acquired in PanIN cells treated with LPS, and in primary fibroblasts and mammary epithelial cells that bypassed Ras‐induced senescence after reduction of ERK signaling. Intriguingly, maintenance of cells that circumvented senescence and acquired stem cell properties was blocked by metformin, an inhibitor of complex I of the electron transport chain or depletion of STAT3, a protein required for mitochondrial functions and stemness. Thus, our studies link bypass of senescence in premalignant lesions to loss of differentiation, acquisition of stemness features, and increased reliance on mitochondrial functions.
- Published
- 2019
16. Healthspan extension, completeness of life and justice.
- Author
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Masny M
- Subjects
- Humans, Social Justice, Dissent and Disputes, Longevity, Aging
- Abstract
Recent progress in geroscience holds the promise of significantly slowing down or even reversing ageing and age-related diseases, and thus increasing our healthspans. In this paper, I offer a novel argument in favour of developing such technology and making it unconditionally available to everyone. In particular, I argue that justice requires that each person be provided with sufficient opportunities to have a 'complete life', that many people currently lack such opportunities, and that we would substantially improve the status quo by giving them access to anti-ageing technology., (© 2022 John Wiley & Sons Ltd.)
- Published
- 2023
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17. Snowbirds and snowflakes: Mobility and aging across the Canada‐United States border.
- Author
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Kelly, Melissa
- Subjects
CANADA-United States relations ,LIFE course approach ,AGING ,SNOWFLAKES ,COMMUNITIES ,GROWTH industries ,STUDENT mobility - Abstract
Copyright of Canadian Geographer is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2023
- Full Text
- View/download PDF
18. Fast three‐dimensional image generation for healthy brain aging using diffeomorphic registration.
- Author
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Fu, Jingru, Tzortzakakis, Antonios, Barroso, José, Westman, Eric, Ferreira, Daniel, and Moreno, Rodrigo
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THREE-dimensional imaging ,MAGNETIC resonance imaging ,AGING ,ALZHEIMER'S disease ,IMAGE registration - Abstract
Predicting brain aging can help in the early detection and prognosis of neurodegenerative diseases. Longitudinal cohorts of healthy subjects scanned through magnetic resonance imaging (MRI) have been essential to understand the structural brain changes due to aging. However, these cohorts suffer from missing data due to logistic issues in the recruitment of subjects. This paper proposes a methodology for filling up missing data in longitudinal cohorts with anatomically plausible images that capture the subject‐specific aging process. The proposed methodology is developed within the framework of diffeomorphic registration. First, two novel modules are introduced within Synthmorph, a fast, state‐of‐the‐art deep learning‐based diffeomorphic registration method, to simulate the aging process between the first and last available MRI scan for each subject in three‐dimensional (3D). The use of image registration also makes the generated images plausible by construction. Second, we used six image similarity measurements to rearrange the generated images to the specific age range. Finally, we estimated the age of every generated image by using the assumption of linear brain decay in healthy subjects. The methodology was evaluated on 2662 T1‐weighted MRI scans from 796 healthy participants from 3 different longitudinal cohorts: Alzheimer's Disease Neuroimaging Initiative, Open Access Series of Imaging Studies‐3, and Group of Neuropsychological Studies of the Canary Islands (GENIC). In total, we generated 7548 images to simulate the access of a scan per subject every 6 months in these cohorts. We evaluated the quality of the synthetic images using six quantitative measurements and a qualitative assessment by an experienced neuroradiologist with state‐of‐the‐art results. The assumption of linear brain decay was accurate in these cohorts (R2 ∈ [.924,.940]). The experimental results show that the proposed methodology can produce anatomically plausible aging predictions that can be used to enhance longitudinal datasets. Compared to deep learning‐based generative methods, diffeomorphic registration is more likely to preserve the anatomy of the different structures of the brain, which makes it more appropriate for its use in clinical applications. The proposed methodology is able to efficiently simulate anatomically plausible 3D MRI scans of brain aging of healthy subjects from two images scanned at two different time points. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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19. Real‐time wrinkle evaluation method using Visual Illusion‐based image feature enhancement System.
- Author
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Fujino, Saori and Iwanaga, Tetsuro
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IMAGE intensifiers ,EVALUATION methodology ,FACIAL creams (Cosmetics) ,JAPANESE people ,DIGITAL images ,JAPANESE women - Abstract
Background: Several advanced methods for evaluating wrinkles are currently available, however, with limitations in their application because wrinkle structures change in response to facial expressions and surrounding environments. A Visual Illusion‐based image feature enhancement System (VIS) was used to develop a real‐time evaluation method. Objectives: This study expands the VIS application into the wrinkle evaluation method by adjusting VIS to evaluate facial wrinkles, evaluating the age‐dependent wrinkles, and validating it for real‐time wrinkle evaluation. Methods: Wrinkles in various Japanese men and women were evaluated using VIS and the current methods. Furthermore, the effectiveness of an eye cream containing niacinamide was evaluated before and after the 4‐week treatment. Results: VIS qualitatively detects even fine wrinkles and numerically records them without any special instrument. Moreover, VIS can be applied to moving images, revealing the effectiveness of the antiwrinkle formulation qualitatively and quantitatively even when the subjects are smiling. Conclusion: This paper presents an epoch‐making wrinkle evaluation method that is qualitative and quantitative, with high sensitivity in real‐time and relies solely on digital images without any difficulties. Therefore, these results imply that this method enables the wrinkle evaluation under real‐life conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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- View/download PDF
20. Contractualist age rationing under outbreak circumstances.
- Author
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Nielsen, Lasse
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LIFE change events ,AGE distribution ,AGE ,MEDICAL care ,DECISION making ,AGING ,COVID-19 pandemic - Abstract
Age rationing is a central issue in the health care priority‐setting literature, but it has become ever more salient in the light of the Covid‐19 outbreak, where health authorities in several countries have given higher priority to younger over older patients. But how is age rationing different under outbreak circumstances than under normal circumstances, and what does this difference imply for ethical theories? This is the topic of this paper. The paper argues that outbreaks such as that of Covid‐19 involve special circumstances that change how age should influence our prioritization decisions, and that while this shift in circumstances poses a problem for consequentialist views such as utilitarianism and age‐weighted consequentialism, contractualism is better equipped to cope with it. The paper then offers a contractualist prudential account of age rationing under outbreak circumstances. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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21. Premature aging is associated with higher levels of 8‐oxoguanine and increased DNA damage in the Polg mutator mouse.
- Author
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Yu, Tenghui, Slone, Jesse, Liu, Wensheng, Barnes, Ryan, Opresko, Patricia L., Wark, Landon, Mai, Sabine, Horvath, Steve, and Huang, Taosheng
- Subjects
MITOCHONDRIAL DNA ,PREMATURE aging (Medicine) ,DNA damage ,NUCLEAR DNA ,DNA polymerases ,REACTIVE oxygen species - Abstract
Mitochondrial dysfunction plays an important role in the aging process. However, the mechanism by which this dysfunction causes aging is not fully understood. The accumulation of mutations in the mitochondrial genome (or "mtDNA") has been proposed as a contributor. One compelling piece of evidence in support of this hypothesis comes from the PolgD257A/D257A mutator mouse (Polgmut/mut). These mice express an error‐prone mitochondrial DNA polymerase that results in the accumulation of mtDNA mutations, accelerated aging, and premature death. In this paper, we have used the Polgmut/mut model to investigate whether the age‐related biological effects observed in these mice are triggered by oxidative damage to the DNA that compromises the integrity of the genome. Our results show that mutator mouse has significantly higher levels of 8‐oxoguanine (8‐oxoGua) that are correlated with increased nuclear DNA (nDNA) strand breakage and oxidative nDNA damage, shorter average telomere length, and reduced mtDNA integrity. Based on these results, we propose a model whereby the increased level of reactive oxygen species (ROS) associated with the accumulation of mtDNA mutations in Polgmut/mut mice results in higher levels of 8‐oxoGua, which in turn lead to compromised DNA integrity and accelerated aging via increased DNA fragmentation and telomere shortening. These results suggest that mitochondrial play a central role in aging and may guide future research to develop potential therapeutics for mitigating aging process. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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22. Facial skin characteristics and concerns in Indonesia: A cross‐sectional observational study.
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Du, Yaping, Doraiswamy, Chandraprabha, Mao, Jie, Zhang, Qian, Liang, Yan, Du, Zheng, Vasantharaghavan, Renuka, and Joshi, Manoj Kumar
- Subjects
HUMAN facial recognition software ,SCALP ,HUMAN skin color ,AGE groups ,CROSS-sectional method ,SCIENTIFIC observation ,LENTIGO - Abstract
Background: Facial skin characteristics and appearance vary according to ethnicity. While much of this knowledge is derived from the Caucasian population, lately there have been efforts to gain such understanding in various regions in Asia. In this paper, we have built an understanding of such features in Indonesia. In Indonesia, a section of females wears a traditional veil (hijab) to cover the scalp and part of face. The influence of the hijab on facial skin attributes was also investigated. Methods: In a cross‐sectional observational study design involving 419 female volunteers in Jakarta, Indonesia, facial skin attributes (colour, radiance, hydration, trans‐epidermal water loss [TEWL], wrinkles, fine lines, pores, and sebum levels) and conditions (melasma, post‐inflammatory hyperpigmentation (PIH), solar lentigines/ senile lentigines, seborrheic keratoses and acne) were assessed by trained operators and dermatologists using standard validated instruments and scales. Results: With age, facial skin colour showed darkening in cheek; forehead on the other hand showed slight lightening. The skin evenness and radiance decreased, substantially. Aging attributes measured in terms of lines, wrinkles, and under‐eye dark circles showed deterioration with age; the decline was progressively faster than colour change. Facial image data analysis corroborated these findings. Skin hydration remained similar across the age groups even though the skin barrier function measured in terms of TEWL improved with age. Sebum levels in the skin were similar up to the age of 50 but declined in the next group of 50–60 year. Pore severity increased with age. Melasma, seborrheic keratosis and PIH showed a high prevalence (>∼50%) at the young age group (20–30 years), itself. Melasma prevalence attained 100% in the age group of 41–50 year and onwards, and its severity similarly showed a steady rise with age. PIH on the other hand showed a steady decline with age. Solar lentigines prevalence (∼30%) did not change much across age groups, and the severity scores were similar in age groups up to 50 year but increased substantially in 51–60‐year age groups. Seborrheic keratosis was similar (∼47%) in age groups up 20–40 year but steadily increased in upper age groups. Its severity was similar in the age groups of 20–30 year and 31–40 year but showed a two‐fold increase in subsequent age groups. Acne was 10% in the age group of 20–30 year and declined gradually to 0.7% in the 51–60‐year age group. Hijab wearers showed slight protection in skin colour darkening and improvement of evenness and radiance but were similar on aging (fine lines and wrinkles on crow's feet, under eye and peri‐oral areas) markers to non‐wearers. In general, in majority of age‐groups, hijab wearers showed a higher prevalence of melasma, solar/senile lentigines, seborrheic keratosis and PIH. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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23. Comment on Comment on "Anomalous structural recovery in the near glass transition range in a polymer glass: Data revisited in light of temperature variability in vacuum oven‐based experiments".
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Jin, Shuang and McKenna, Gregory B.
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GLASS transitions ,GLASS transition temperature ,TEMPERATURE control ,VINYL chloride ,TEMPERATURE ,CREEP (Materials) - Abstract
Cangialosi, Alegría, and Colmenero have made a comment on a paper of ours [Polym. Eng. Sci. 2022:1–13], in which we discussed the concern that the enthalpy recovery data reported by Cangialosi and co‐workers [Phys. Rev. Lett. 2013;111(9):095701] for polystyrene aged up to 15 K below glass transition temperature was anomalous and contradicted existing experimental results from the literature over a similar range of aging conditions. Their response shifts the focus away from the raised questions about their experimental results and attempts to invalidate the data that we cited in support of our argument. Here we respond to the comment and add additional analysis that suggests the structural recovery response of glassy materials exhibits smooth behavior over the full range of measurements, up to 7 or 8 logarithmic decades. We do this by referring to the work on the intrinsic isotherm down‐jump and memory responses of poly(vinyl acetate) between 40°C and 15°C over six logarithmic decades by Kovacs [Fortsch. Hochpolym. Fo. 1963;3(1/2):394–508], the small‐strain tensile creep of poly(vinyl chloride) quenched from 90°C to 40°C (approximately 40°C below Tg) over seven logarithmic decades from Struik [Polym Eng. Sci., 1977;17:165–173], and the volume recovery behavior for aging times up to 3 months in a temperature range between 95°C and −50°C by Greiner and Schwarzl [Rheol. Acta. 1984;23(4):378–395]. We also add discussion that an isothermal aging procedure using a vacuum oven is highly vulnerable to temperature errors due to the problem of good temperature control when the heat transfer mechanism is primarily radiative. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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24. Letter to the Editor regarding "Opportunistic screening with CT: comparison of phantomless BMD calibration methods".
- Author
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Boyd, Steven K, Manske, Sarah L, Matheson, Bryn, Smith, Ainsley, and Bott, Kirsten
- Abstract
This letter to the editor responds to a paper that explores methods for performing density calibration on CT data to calculate bone mineral density (BMD) in the absence of a calibration phantom. The authors of the letter highlight the advantages of the "voxel-specific" method, which does not require direct measurements on the CT scanner and can be applied in settings where access to the scanner is unavailable. They express concerns about the implementation of their method by the authors of the original paper and argue that the conclusions about the poor suitability of the voxel-specific calibration may be overstated. The authors invite others in the scientific community to find solutions through open science. [Extracted from the article]
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- 2024
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25. The peak‐shift method for the description of structural relaxation in glassy materials: a critical review.
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Svoboda, Roman
- Subjects
- *
GLASS transition temperature , *GLASS transitions , *AMORPHOUS substances , *ACTIVATION energy - Abstract
Nowadays, the glass transition kinetics is most commonly described in terms of the Tool–Narayanaswamy–Moynihan (TNM) model. Evaluation of one of the most prominent features of the structural relaxation motions—the relaxation nonlinearity—was traditionally done using the peak‐shift (PS) method. This paper introduces, for the first time, extensive testing of the PS method by means of theoretical simulations for all practically observable types of structural relaxation behavior and all types of glassy/amorphous materials (tested range of the glass transition temperatures: −55 to 1000°C; tested range of the relaxation activation energies: 300–1300 kJ⋅mol−1). For the majority of types of structural relaxation behavior, the PS method tends to slightly overestimate the value of the TNM nonlinearity parameter x (by ∼ 0.05–0.10). In the specific cases of the highly linear behavior (↑ x) combined with a broad distribution of relaxation times, the PS method systematically vastly underestimates the value of x. A new, improved temperature program was proposed for the PS method, eliminating the major intrinsic drawback of the originally proposed version of the PS methodology. In addition, based on the comparison between the theoretically simulated and real‐life experimental data, a new approach (based on the characteristic PS dependence shape) was introduced to estimate the width of the relaxation times distribution. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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26. On older person/place transformations: Towards a more‐than‐representational geography of aging in rural Canada.
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Hanlon, Neil and Skinner, Mark W.
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OLDER people ,GEOGRAPHY ,RURAL population ,POPULATION aging ,RURAL geography ,ECONOMIC change ,INTERNAL migration ,AGING - Abstract
Copyright of Canadian Geographer is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2022
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27. Let's talk about sex: older people's views on the recognition of sexuality and sexual health in the health-care setting.
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Bauer, Michael, Haesler, Emily, and Fetherstonhaugh, Deirdre
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AGE distribution ,AGING ,CINAHL database ,DATABASES ,SEXUAL health ,MEDICAL information storage & retrieval systems ,MEDICAL care ,MEDLINE ,META-analysis ,PATIENTS ,RESEARCH funding ,QUALITATIVE research ,LITERATURE reviews ,QUANTITATIVE research ,WELL-being ,ACQUISITION of data - Abstract
Objective: To report on the findings of a systematic review which examined the experiences and views of older people aged 65 years and over on health professionals’ recognition of sexuality and sexual health and whether these aspects of the person are incorporated into care. Review methods: The review followed the methods laid out by the Joanna Briggs Institute. Eleven electronic databases were searched using the terms sexual*, aged, ageing/aging, attitudes and care in any health‐care setting. Only quantitative and qualitative research and opinion papers written in English and offering unique commentary published between January 2004 and January 2015 were eligible. Results: A total of 999 papers were initially identified and of these, 148 were assessed by two reviewers. Eighteen studies – seven quantitative, eight qualitative and three opinion papers – met the inclusion criteria and were appraised. The importance of sexuality to well‐being, language used, expressing sexuality, discomfort discussing sexuality, inadequate sexuality health education and treatment and deficient communication with health‐care professionals were all identified as significant issues in a range of settings. Fourteen categories and five syntheses summarize the 43 findings. Conclusions: Sexuality remains important for many older people; however, embarrassment, dissatisfaction with treatment, negative attitudes and seeming disinterest by health professionals can all inhibit discussions. Professionals and health‐care services need to adopt strategies and demonstrate characteristics which create environments that are more supportive of sexuality. Issues related to sexuality and sexual health should be able to be discussed without anxiety or discomfort so that older people receive optimal care and treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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28. Preserving transcriptional stress responses as an anti-aging strategy.
- Author
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Cheng Y, Pitoniak A, Wang J, and Bohmann D
- Subjects
- Animals, Drosophila melanogaster genetics, Aging genetics, Drosophila Proteins genetics, Repressor Proteins genetics
- Abstract
The progressively increasing frailty, morbidity and mortality of aging organisms coincides with, and may be causally related to, their waning ability to adapt to environmental perturbations. Transcriptional responses to challenges, such as oxidative stress or pathogens, diminish with age. This effect is manifest in the declining function of the stress responsive transcription factor Nrf2. Protective gene expression programs that are controlled by the Drosophila Nrf2 homolog, CncC, support homeostasis and longevity. Age-associated chromatin changes make these genes inaccessible to CncC binding and render them inert to signal-dependent transcriptional activation in old animals. In a previous paper, we have reported that overexpression of the CncC dimerization partner Maf-S counteracts this degenerative effect and preserves organism fitness. Building on this work, we show here that Maf-S overexpression prevents loss of chromatin accessibility and maintains gene responsiveness. Moreover, the same outcome, along with an extension of lifespan, can be achieved by inducing CncC target gene expression pharmacologically throughout adult life. Thus, pharmacological or dietary interventions that can preserve stress responsive gene expression may be feasible anti-aging strategies., (© 2021 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
- Published
- 2021
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29. Record Stability for Fully Passive Perovskite‐Based X‐Ray Detectors Through the Use of Starch as Templating Agent.
- Author
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Verdi, Matteo, Giuri, Antonella, Ciavatti, Andrea, Rizzo, Aurora, Esposito Corcione, Carola, Basiricò, Laura, Colella, Silvia, and Fraboni, Beatrice
- Subjects
DETECTORS ,PEROVSKITE ,STARCH ,X-ray detection ,PASSIVE components ,RADIOGRAPHIC films - Abstract
High sensitivity and efficient X‐ray detectors are needed to promote and boost their application as tools in medical diagnostics and radiotherapy. Lead halide perovskites have emerged recently as a novel class of material for efficient X‐ray detection. Although 3D perovskites possess very interesting optoelectronic properties they suffer from low environmental and operational stability. Here a strategy based on using starch as a polymeric template for the fabrication of stable thin film perovskite X‐ray detectors is reported. The proposed p‐i‐n photodiodes can operate with no external bias applied (fully passive devices), reaching a top sensitivity of 5.5 ± 0.2 µC Gy−1 s−1. The device degradation is monitored for samples stored in air for a time window of 630 days, demonstrating exceptional stability: 97% of the initial sensitivity is retained for the best perovskite‐starch composite formulation making it the most stable unencapsulated perovskite X‐ray detector reported so far. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
30. Characterization of thermal aging effects on the creep performance of T91 using small punch creep testing.
- Author
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Ó'Murchú, Cathal, Leen, Seán B., O'Donoghue, Padraic E., and Barrett, Richard A.
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DETERIORATION of materials ,CREEP (Materials) ,TENSILE tests ,PUNCHING (Metalwork) ,HIGH temperatures ,TEST methods - Abstract
This paper is concerned with the development and application of a small punch creep testing method for assessment of the effects of thermal aging and associated precipitate coarsening on the high temperature creep life and deformation behavior of a 9Cr ferritic–martensitic steel. The tests are conducted on P91 steel, for both aged (up to 1 year) and unaged specimens, at temperatures of 600°C. The unaged test results are shown to be consistent with previously published creep tensile test rupture life data in terms of Chakrabarty membrane stress. Aging is shown to have a significant, detrimental effect on creep life and deformation rate. The steady‐state displacement rate, time to failure, and displacement at failure data, for both aged and unaged, were successfully correlated via the modified Monkman–Grant relationship. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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- View/download PDF
31. Financing Long-Term Services and Supports: Ideas From Singapore.
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GRAHAM, WAN CHEN KANG and BILGER, MARCEL
- Subjects
- *
PUBLIC health & economics , *LONG-term health care , *LONG-term care insurance , *PUBLIC health , *AGING , *CHARITABLE giving , *INCOME , *HEALTH policy , *PUBLIC welfare , *RESPONSIBILITY , *RETIREMENT , *GOVERNMENT aid , *ECONOMICS - Abstract
Policy Points:In Singapore, long‐term services and supports (LTSS) are financed through a mix of public and private sources comprising tiered means‐tested public subsidies and government grants to care providers, charitable donations, voluntary long‐term care insurance, and other private resources.Singapore's high take‐up rate of voluntary long‐term care insurance is explained by plans offering partial coverage, medical underwriting, early automatic enrollment, direct debit of insurance premiums, and defined cash benefits.Singapore's experience in long‐term care financing is relevant to the US debate, as it provides policy ideas that may be transferable to the American context.We recommend maximizing the population's total contribution to voluntary long‐term care insurance by striking the right balance between coverage adequacy and take‐up rate while targeting subsidies to low‐income individuals. Context: Financing long‐term services and supports (LTSS) for the elderly is a pressing issue in the United States with reforms of long‐term care insurance (LTCI) presently being explored. Singapore, with 65% of residents aged 40 to 83 covered by basic LTCI, including 22% with supplementary LTCI plans, has the highest voluntary LTCI rate in the world. This article contributes to the discourse by presenting the case of LTSS financing in Singapore. Methods: We first reviewed Singapore's LTSS policies through a comprehensive search of academic papers, governmental reports, parliamentary debate transcripts, print media, and official websites of LTSS providers. We then estimated the LTSS financing mix, conducted an in‐depth analysis of the main policies, and illustrated the financial protection they procure for the elderly using realistic hypothetical scenarios. Findings: The main principles governing Singapore's LTSS policies are shared responsibility for long‐term care financing, targeted assistance for the poor, centralized governance and administration, separation from other income and housing policies, and limited intergenerational cross‐subsidizing. We estimate the financing mix to consist of out‐of‐pocket spending (40%), government spending (42%), long‐term care insurance (9%), and charitable donations (9%). Assuming a monthly LTSS bill of US$1,545 to US$2,575, between 11% and 19% of LTSS expense is offset by LTCI for severely disabled individuals with basic coverage. Overall, 63% of care recipients are eligible for public subsidies that amount to 20% to 80% of their expenses. Conclusions: The high take‐up of voluntary LTCI in Singapore is explained by the high prevalence of plans offering partial coverage, medical underwriting, early automatic enrollment, direct debit of insurance premiums, and defined cash benefits. We recommend setting the coverage of voluntary long‐term care insurance plans at levels that maximize the population's total contribution by striking the right balance between coverage adequacy and take‐up rate while targeting subsidies to low‐income individuals. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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32. Temporal pattern of neuronal insulin release during Caenorhabditis elegans aging: Role of redox homeostasis.
- Author
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Minniti AN, Arriagada H, Zúñiga S, Bravo-Zehnder M, Alfaro IE, and Aldunate R
- Subjects
- Acetylcysteine pharmacology, Aging drug effects, Animals, Antioxidants pharmacology, Caenorhabditis elegans drug effects, Caenorhabditis elegans Proteins metabolism, Down-Regulation drug effects, Longevity drug effects, Models, Biological, Motor Activity drug effects, Mutation genetics, Neurons drug effects, Oxidation-Reduction, Reproduction drug effects, Signal Transduction drug effects, Time Factors, Aging physiology, Caenorhabditis elegans physiology, Homeostasis drug effects, Insulin metabolism, Neurons metabolism
- Abstract
The insulin-IGF-1/DAF-2 pathway has a central role in the determination of aging and longevity in Caenorhabditis elegans and other organisms. In this paper, we measured neuronal insulin secretion (using INS-22::Venus) during C. elegans lifespan and monitored how this secretion is modified by redox homeostasis. We showed that INS-22::Venus secretion fluctuates during the organism lifetime reaching maximum levels in the active reproductive stage. We also demonstrate that long-lived daf-2 insulin receptor mutants show remarkable low levels of INS-22::Venus secretion. In contrast, we found that short-lived mutant worms that lack the oxidation repair enzyme MSRA-1 show increased levels of INS-22::Venus secretion, specifically during the reproductive stage. MSRA-1 is a target of the insulin-IGF-1/DAF-2 pathway, and the expression of this antioxidant enzyme exclusively in the nervous system rescues the mutant insulin release phenotype and longevity. The msra-1 mutant phenotype can also be reverted by antioxidant treatment during the active reproductive stage. We showed for the first time that there is a pattern of neuronal insulin release with a noticeable increment during the peak of reproduction. Our results suggest that redox homeostasis can modulate longevity through the regulation of insulin secretion, and that the insulin-IGF-1/DAF-2 pathway could be regulated, at least in part, by a feedback loop. These findings highlight the importance of timing for therapeutic interventions aimed at improving health span., (© 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
- Published
- 2019
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33. The involvement of stress granules in aging and aging‐associated diseases.
- Author
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Cao, Xiuling, Jin, Xuejiao, and Liu, Beidong
- Subjects
AGE factors in disease ,SCAFFOLD proteins ,CONDITIONED response ,RNA-binding proteins ,QUALITY control ,BIOCHEMICAL engineering - Abstract
Stress granules (SGs) are nonmembrane assemblies formed in cells in response to stress conditions. SGs mainly contain untranslated mRNA and a variety of proteins. RNAs and scaffold proteins with intrinsically disordered regions or RNA‐binding domains are essential for the assembly of SGs, and multivalent macromolecular interactions among these components are thought to be the driving forces for SG assembly. The SG assembly process includes regulation through post‐translational modification and involvement of the cytoskeletal system. During aging, many intracellular bioprocesses become disrupted by factors such as cellular environmental changes, mitochondrial dysfunction, and decline in the protein quality control system. Such changes could lead to the formation of aberrant SGs, as well as alterations in their maintenance, disassembly, and clearance. These aberrant SGs might in turn promote aging and aging‐associated diseases. In this paper, we first review the latest progress on the molecular mechanisms underlying SG assembly and SG functioning under stress conditions. Then, we provide a detailed discussion of the relevance of SGs to aging and aging‐associated diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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- View/download PDF
34. Modelling hospital readmissions under frailty conditions for healthy aging.
- Author
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Graña, Manuel, Lopez‐Guede, Jose Manuel, Irazusta, Jon, Labayen, Idoia, and Besga, Ariadna
- Subjects
PATIENT readmissions ,OLDER people ,AGING ,HOSPITAL admission & discharge ,FORECASTING ,UNIVERSITY hospitals - Abstract
In the current context of an aging population in many developed countries, the issue of healthy aging is at the forefront of the political, scientific, and technological concerns. The frailty accompanying the late years of elderly people (>70 years old) deserves special consideration due to its great economical and personal costs and the workload imposed on the health care system. Hospital readmissions under a short time after hospital discharge are one of the sources of concern, and much effort is being devoted to their prediction for better care of the elder and optimized resource management. In this paper, we consider the prediction of readmissions for patients that are evaluated positively in the frailty scales. The computational experiments are carried out over a gender‐balanced cohort of 645 patients recruited at the University Hospital of Alava. We report machine‐learning prediction results of the readmission before the standard readmission limit of 30 days. We apply an upsampling technique to correct for class imbalance. Results are positive, encouraging further research and the creation of larger cohorts in international efforts. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
35. Research progress on immune aging and its mechanisms affecting geriatric diseases.
- Author
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Yu, Yanping and Zheng, Songbai
- Subjects
AGING ,IMMUNOSENESCENCE ,IMMUNE system ,DISEASES in older people ,DISEASE susceptibility - Abstract
Immunosenescence, also known as immune aging, refers to the degeneration, compensation, and reconstruction of the immune system with aging. Immune aging is an important factor in the increased susceptibility of the elderly to infectious diseases, malignant tumors, and a variety of chronic diseases and has long been a hotspot in geriatrics and immunology research. In this paper, the characteristics and progression of immune aging are briefly reviewed for clinicians' reference. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
36. Ageing, Optimal National Saving and Future Living Standards in Australia.
- Author
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Guest, Ross S. and McDonald, Ian M.
- Subjects
AUSTRALIAN economy ,AGING ,STANDARD of living - Abstract
Making allowance for the ageing structure of the population, this paper calculates the levels of optimal national saving and future living standards for Australia for the period 1999-2050. For this period, the optimal saving response to the ageing of the Australian population is for national saving to increase from its current level by 2.7 per cent of GDP by the year 2017 and then to decline to the year 2050. The implied growth of living standards is 1.20 per cent per year. Reduced immigration would reduce the rate of growth of living standards but reduced fertility would not. [ABSTRACT FROM AUTHOR]
- Published
- 2001
- Full Text
- View/download PDF
37. Population Ageing and Projections of Government Social Outlays in Australia.
- Author
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Guest, Ross S. and McDonald, M.
- Subjects
AGING ,ECONOMIC aspects of aging ,POPULATION ,OLD age assistance ,TAXATION -- Social aspects ,GOVERNMENT spending policy ,GROSS domestic product ,SOCIAL security ,TAXATION ,ECONOMIC policy - Abstract
This paper makes new projections of government social outlays for Australia. The calculations suggest that government social outlays will increase considerably as a percentage of GDP over the next 50 years; by 7.3 per cent of GDP in the base case. This is a greater increase than that found by previous investigation. Over 60 per cent of this increase will occur between 2011 and 2031, the years when the baby boom generation retires. The major contribution to this increase will have come from increased government outlays on social security. Lower rates of net immigration are shown to yield an even larger increase in the percentage of government social outlays in GDP. The paper also considers the disincentive effect of taxation and the effect of increasing the age of retirement. However, notwithstanding the trends suggested by the projections, the paper argues that there are a number of reasons to be sanguine about the implications of ageing on the share of government outlays in GDP. [ABSTRACT FROM AUTHOR]
- Published
- 2000
- Full Text
- View/download PDF
38. Nrf2 activation by pyrroloquinoline quinone inhibits natural aging‐related intervertebral disk degeneration in mice.
- Author
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Xue, Qi, Li, Jie, Qin, Ran, Li, Mingying, Li, Yiping, Zhang, Jing, Wang, Rong, Goltzman, David, Miao, Dengshun, and Yang, Renlei
- Abstract
Age‐related intervertebral disk degeneration (IVDD) involves increased oxidative damage, cellular senescence, and matrix degradation. Pyrroloquinoline quinone (PQQ) is a water‐soluble vitamin‐like compound with strong anti‐oxidant capacity. The goal of this study was to determine whether PQQ can prevent aging‐related IVDD, and the underlying mechanism. Here, we found that dietary PQQ supplementation for 12 months alleviated IVDD phenotypes in aged mice, including increased disk height index and reduced histological scores and cell loss, without toxicity. Mechanistically, PQQ inhibited oxidative stress, cellular senescence, and senescence‐associated secretory phenotype (SASP) in the nucleus pulposus and annulus fibrosus of aged mice. Similarly, PQQ protected against interleukin‐1β‐induced matrix degradation, reactive oxygen species accumulation, and senescence in human nucleus pulposus cells (NPCs) in vitro. Molecular docking predicted and biochemical assays validated that PQQ interacts with specific residues to dissociate the Keap1–Nrf2 complex, thereby increasing nuclear Nrf2 translocation and activation of Nrf2‐ARE signaling. RNA sequencing and luciferase assays revealed Nrf2 can transcriptionally upregulate Wnt5a by binding to its promoter, while Wnt5a knockdown prevented PQQ inhibition of matrix metalloproteinase‐13 in NPCs. Notably, PQQ supplementation failed to alleviate aging‐associated IVDD phenotypes and oxidative stress in aged Nrf2 knockout mice, indicating Nrf2 is indispensable for PQQ bioactivities. Collectively, this study demonstrates Nrf2 activation by PQQ inhibits aging‐induced IVDD by attenuating cellular senescence and matrix degradation. This study clarifies Keap1–Nrf2–Wnt5a axis as the novel signaling underlying the protective effects of PQQ against aging‐related IVDD, and provides evidence for PQQ as a potential agent for clinical prevention and treatment of natural aging‐induced IVDD. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
39. Integrated multi‐omic analyses uncover the effects of aging on cell‐type regulation in glucose‐responsive tissues.
- Author
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Xu, Peng, Kong, Yimeng, Palmer, Nicholette D., Ng, Maggie C. Y., Zhang, Bin, and Das, Swapan K.
- Abstract
Aging significantly influences cellular activity and metabolism in glucose‐responsive tissues, yet a comprehensive evaluation of the impacts of aging and associated cell‐type responses has been lacking. This study integrates transcriptomic, methylomic, single‐cell RNA sequencing, and metabolomic data to investigate aging‐related regulations in adipose and muscle tissues. Through coexpression network analysis of the adipose tissue, we identified aging‐associated network modules specific to certain cell types, including adipocytes and immune cells. Aging upregulates the metabolic functions of lysosomes and downregulates the branched‐chain amino acids (BCAAs) degradation pathway. Additionally, aging‐associated changes in cell proportions, methylation profiles, and single‐cell expressions were observed in the adipose. In the muscle tissue, aging was found to repress the metabolic processes of glycolysis and oxidative phosphorylation, along with reduced gene activity of fast‐twitch type II muscle fibers. Metabolomic profiling linked aging‐related alterations in plasma metabolites to gene expression in glucose‐responsive tissues, particularly in tRNA modifications, BCAA metabolism, and sex hormone signaling. Together, our multi‐omic analyses provide a comprehensive understanding of the impacts of aging on glucose‐responsive tissues and identify potential plasma biomarkers for these effects. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
40. Maternal age is related to offspring DNA methylation: A meta‐analysis of results from the PACE consortium.
- Author
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Yeung, Edwina, Biedrzycki, Richard J., Gómez Herrera, Laura C., Issarapu, Prachand, Dou, John, Marques, Irene Fontes, Mansuri, Sohail Rafik, Page, Christian Magnus, Harbs, Justin, Khodasevich, Dennis, Poisel, Eric, Niu, Zhongzheng, Allard, Catherine, Casey, Emma, Berstein, Fernanda Morales, Mancano, Giulia, Elliott, Hannah R., Richmond, Rebecca, He, Yiyan, and Ronkainen, Justiina
- Abstract
Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta‐analyzed epigenome‐wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5–10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR < 0.05). Eight of these CpGs were located near/in the MTNR1B gene, coding for a melatonin receptor. Regional analysis identified them together as a differentially methylated region consisting of 9 CpGs in/near MTNR1B, at which higher DNAm was associated with greater maternal age (PFDR = 6.92 × 10−8) in newborns. In childhood blood samples, these differences in blood DNAm of MTNR1B CpGs were nominally significant (p < 0.05) and retained the same positive direction, suggesting persistence of associations. Maternal age was also positively associated with higher DNA methylation at three CpGs in RTEL1‐TNFRSF6B at birth (PFDR < 0.05) and nominally in childhood (p < 0.0001). Of the remaining 10 CpGs also persistent in childhood, methylation at cg26709300 in YPEL3/BOLA2B in external data was associated with expression of ITGAL, an immune regulator. While further study is needed to establish causality, particularly due to the small effect sizes observed, our results potentially support offspring DNAm as a mechanism underlying associations of maternal age with child health. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
41. Validity of the MoCA as a cognitive screening tool in epilepsy: Are there implications for global care and research?
- Author
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Reyes, Anny, Hermann, Bruce P., Prabhakaran, Divya, Ferguson, Lisa, Almane, Dace N., Shih, Jerry J., Iragui‐Madoz, Vicente J., Struck, Aaron, Punia, Vineet, Jones, Jana E., Busch, Robyn M., and McDonald, Carrie R.
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COGNITIVE processing speed ,MONTREAL Cognitive Assessment ,PARTIAL epilepsy ,COGNITIVE aging ,OLDER people ,NEUROPSYCHOLOGICAL tests - Abstract
Objective: This study evaluated the diagnostic performance of a widely available cognitive screener, the Montreal cognitive assessment (MoCA), to detect cognitive impairment in older patients (age ≥ 55) with epilepsy residing in the US, using the International Classification of Cognitive Disorders in Epilepsy (IC‐CoDE) as the gold standard. Methods: Fifty older adults with focal epilepsy completed the MoCA and neuropsychological measures of memory, language, executive function, and processing speed/attention. The IC‐CoDE taxonomy divided participants into IC‐CoDE Impaired and Intact groups. Sensitivity and specificity across several MoCA cutoffs were examined. Spearman correlations examined relationships between the MoCA total score and clinical and demographic variables and MoCA domain scores and individual neuropsychological tests. Results: IC‐CoDE impaired patients demonstrated significantly lower scores on the MoCA total, visuospatial/executive, naming, language, delayed recall, and orientation domain scores (Cohen's d range: 0.336–2.77). The recommended MoCA cutoff score < 26 had an overall accuracy of 72%, 88.2% sensitivity, and 63.6% specificity. A MoCA cutoff score < 24 yielded optimal sensitivity (70.6%) and specificity (78.8%), with overall accuracy of 76%. Higher MoCA total scores were associated with greater years of education (p = 0.016) and fewer antiseizure medications (p = 0.049). The MoCA memory domain was associated with several standardized measures of memory, MoCA language domain with category fluency, and MoCA abstraction domain with letter fluency. Significance: This study provides initial validation of the MoCA as a useful screening tool for older adults with epilepsy that can be used to identify patients who may benefit from comprehensive neuropsychological testing. Further, we demonstrate that a lower cutoff (i.e., <24) better captures cognitive impairment in older adults with epilepsy than the generally recommended cutoff and provides evidence for construct overlap between MoCA domains and standard neuropsychological tests. Critically, similar efforts in other regions of the world are needed. Plain Language Summary: The Montreal cognitive assessment (MoCA) can be a helpful tool to screen for cognitive impairment in older adults with epilepsy. We recommend that adults 55 or older with epilepsy who score less than 24 on the MoCA are referred to a neuropsychologist for a comprehensive evaluation to assess any changes in cognitive abilities and mood. [ABSTRACT FROM AUTHOR]
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- 2024
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42. Age‐related changes in cheek skin movement: A case study of Japanese women.
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Kurosumi, Motonori, Yabuzaki, Jiro, Kuribayashi, Mari, and Mizukoshi, Koji
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JAPANESE women ,SKIN aging ,FACIAL expression ,CHEEK ,MOTION capture (Human mechanics) ,AGE groups ,FACIAL muscles - Abstract
Background: The majority of conventional studies on skin aging have focused on static conditions. However, in daily life, the facial skin we encounter is constantly in motion due to conversational expressions and changes in facial expressions, causing the skin to alter its position and shape, resulting in a dynamic state. Consequently, it is hypothesized that characteristics of aging not apparent in static conditions may be present in the dynamic state of the skin. Therefore, this study investigates age‐related changes in dynamic skin characteristics associated with facial expression alterations. Methods: A motion capture system measured the dynamic characteristics (delay and stretchiness of skin movement associated with expression) of the cheek skin in response to facial expressions among 86 Japanese women aged between 20 and 69 years. Results: The findings revealed an increase in the delay of cheek skin response to facial expressions (r = 0.24, p < 0.05) and a decrease in the stretchiness of the lower cheek area with age (r = 0.60, p < 0.01). An increasing variance in delay and stretchiness within the same age group was also observed with aging. Conclusion: The findings of this study revealed that skin aging encompasses both static characteristics, such as spots, wrinkles, and sagging, traditionally studied in aging research, and dynamic aging characteristics of the skin that emerge in response to facial expression changes. These dynamic aging characteristics could pave the way for the development of new methodologies in skin aging analysis and potentially improve our understanding and treatment of aging impressions that are visually perceptible in daily life but remain unexplored. [ABSTRACT FROM AUTHOR]
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- 2024
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43. Translatability of life‐extending pharmacological treatments between different species.
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Burdusel, Daiana, Coman, Cristin, Ancuta, Diana–Larisa, Hermann, Dirk M., Doeppner, Thorsten R., Gresita, Andrei, and Popa‐Wagner, Aurel
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DRUG therapy ,BIOCOMPLEXITY ,BIOLOGICAL systems ,SPECIES ,LONGEVITY ,LIFE spans ,AGING prevention - Abstract
Anti‐aging research has made significant strides in identifying treatments capable of extending lifespan across a range of organisms, from simple invertebrates to mammals. This review showcases the current state of anti‐aging interventions, highlighting the lifespan extensions observed in animal models through various treatments and the challenges encountered in translating these findings to humans. Despite promising results in lower organisms, the translation of anti‐aging treatments to human applications presents a considerable challenge. This discrepancy can be attributed to the increasing complexity of biological systems, species‐specific metabolic and genetic differences, and the redundancy of metabolic pathways linked to longevity. Our review focuses on analyzing these challenges, offering insights into the efficacy of anti‐aging mechanisms across species and identifying key barriers to their translation into human treatments. By synthesizing current knowledge and identifying gaps in translatability, this review aims to underscore the importance of advancing these therapies for human benefit. Bridging this gap is essential to assess the potential of such treatments in extending the human healthspan. [ABSTRACT FROM AUTHOR]
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- 2024
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44. Neuronal microstructural changes in the human brain are associated with neurocognitive aging.
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Singh, Kavita, Barsoum, Stephanie, Schilling, Kurt G., An, Yang, Ferrucci, Luigi, and Benjamini, Dan
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GRAY matter (Nerve tissue) ,DIFFUSION magnetic resonance imaging ,ALZHEIMER'S disease ,AGING ,COGNITIVE testing ,MEMBRANE permeability (Biology) - Abstract
Gray matter (GM) alterations play a role in aging‐related disorders like Alzheimer's disease and related dementias, yet MRI studies mainly focus on macroscopic changes. Although reliable indicators of atrophy, morphological metrics like cortical thickness lack the sensitivity to detect early changes preceding visible atrophy. Our study aimed at exploring the potential of diffusion MRI in unveiling sensitive markers of cortical and subcortical age‐related microstructural changes and assessing their associations with cognitive and behavioral deficits. We leveraged the Human Connectome Project‐Aging cohort that included 707 participants (394 female; median age = 58, range = 36–90 years) and applied the powerful mean apparent diffusion propagator model to measure microstructural parameters, along with comprehensive behavioral and cognitive test scores. Both macro‐ and microstructural GM characteristics were strongly associated with age, with widespread significant microstructural correlations reflective of cellular morphological changes, reduced cellular density, increased extracellular volume, and increased membrane permeability. Importantly, when correlating MRI and cognitive test scores, our findings revealed no link between macrostructural volumetric changes and neurobehavioral performance. However, we found that cellular and extracellular alterations in cortical and subcortical GM regions were associated with neurobehavioral performance. Based on these findings, it is hypothesized that increased microstructural heterogeneity and decreased neurite orientation dispersion precede macrostructural changes, and that they play an important role in subsequent cognitive decline. These alterations are suggested to be early markers of neurocognitive performance that may distinctly aid in identifying the mechanisms underlying phenotypic aging and subsequent age‐related functional decline. [ABSTRACT FROM AUTHOR]
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- 2024
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45. NMR metabolomic modeling of age and lifespan: A multicohort analysis.
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Lau, Chung‐Ho E., Manou, Maria, Markozannes, Georgios, Ala‐Korpela, Mika, Ben‐Shlomo, Yoav, Chaturvedi, Nish, Engmann, Jorgen, Gentry‐Maharaj, Aleksandra, Herzig, Karl‐Heinz, Hingorani, Aroon, Järvelin, Marjo‐Riitta, Kähönen, Mika, Kivimäki, Mika, Lehtimäki, Terho, Marttila, Saara, Menon, Usha, Munroe, Patricia B., Palaniswamy, Saranya, Providencia, Rui, and Raitakari, Olli
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METABOLOMICS ,CHRONIC obstructive pulmonary disease ,CAROTID intima-media thickness ,NUCLEAR magnetic resonance spectroscopy ,AGE - Abstract
Metabolomic age models have been proposed for the study of biological aging, however, they have not been widely validated. We aimed to assess the performance of newly developed and existing nuclear magnetic resonance spectroscopy (NMR) metabolomic age models for prediction of chronological age (CA), mortality, and age‐related disease. Ninety‐eight metabolic variables were measured in blood from nine UK and Finnish cohort studies (N ≈31,000 individuals, age range 24–86 years). We used nonlinear and penalized regression to model CA and time to all‐cause mortality. We examined associations of four new and two previously published metabolomic age models, with aging risk factors and phenotypes. Within the UK Biobank (N ≈102,000), we tested prediction of CA, incident disease (cardiovascular disease (CVD), type‐2 diabetes mellitus, cancer, dementia, and chronic obstructive pulmonary disease), and all‐cause mortality. Seven‐fold cross‐validated Pearson's r between metabolomic age models and CA ranged between 0.47 and 0.65 in the training cohort set (mean absolute error: 8–9 years). Metabolomic age models, adjusted for CA, were associated with C‐reactive protein, and inversely associated with glomerular filtration rate. Positively associated risk factors included obesity, diabetes, smoking, and physical inactivity. In UK Biobank, correlations of metabolomic age with CA were modest (r = 0.29–0.33), yet all metabolomic model scores predicted mortality (hazard ratios of 1.01 to 1.06/metabolomic age year) and CVD, after adjustment for CA. While metabolomic age models were only moderately associated with CA in an independent population, they provided additional prediction of morbidity and mortality over CA itself, suggesting their wider applicability. [ABSTRACT FROM AUTHOR]
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- 2024
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46. Methylation entropy landscape of Chinese long‐lived individuals reveals lower epigenetic noise related to human healthy aging.
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Wang, Hao‐Tian, Xiao, Fu‐Hui, Gao, Zong‐Liang, Guo, Li‐Yun, Yang, Li‐Qin, Li, Gong‐Hua, and Kong, Qing‐Peng
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LONGEVITY ,EPIGENETICS ,WHOLE genome sequencing ,AGING ,ENTROPY ,AGE ,NOISE - Abstract
The transition from ordered to noisy is a significant epigenetic signature of aging and age‐related disease. As a paradigm of healthy human aging and longevity, long‐lived individuals (LLI, >90 years old) may possess characteristic strategies in coping with the disordered epigenetic regulation. In this study, we constructed high‐resolution blood epigenetic noise landscapes for this cohort by a methylation entropy (ME) method using whole genome bisulfite sequencing (WGBS). Although a universal increase in global ME occurred with chronological age in general control samples, this trend was suppressed in LLIs. Importantly, we identified 38,923 genomic regions with LLI‐specific lower ME (LLI‐specific lower entropy regions, for short, LLI‐specific LERs). These regions were overrepresented in promoters, which likely function in transcriptional noise suppression. Genes associated with LLI‐specific LERs have a considerable impact on SNP‐based heritability of some aging‐related disorders (e.g., asthma and stroke). Furthermore, neutrophil was identified as the primary cell type sustaining LLI‐specific LERs. Our results highlight the stability of epigenetic order in promoters of genes involved with aging and age‐related disorders within LLI epigenomes. This unique epigenetic feature reveals a previously unknown role of epigenetic order maintenance in specific genomic regions of LLIs, which helps open a new avenue on the epigenetic regulation mechanism in human healthy aging and longevity. [ABSTRACT FROM AUTHOR]
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- 2024
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47. Aging and intraocular pressure homeostasis in mice.
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Li, Guorong, van Batenburg‐Sherwood, Joseph, Safa, Babak N., Fraticelli Guzmán, Nina Sara, Wilson, Andrea, Bahrani Fard, Mohammad Reza, Choy, Kevin, de Ieso, Michael L., Cui, J. Serena, Feola, Andrew J., Weisz, Tara, Kuhn, Megan, Bowes Rickman, Catherine, Farsiu, Sina, Ethier, C. Ross, and Stamer, W. Daniel
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INTRAOCULAR pressure ,AQUEOUS humor ,CELLULAR aging ,SCHLEMM'S canal ,OCULAR hypertension ,HOMEOSTASIS ,AGING ,LABORATORY mice - Abstract
Age and elevated intraocular pressure (IOP) are the two primary risk factors for glaucoma, an optic neuropathy that is the leading cause of irreversible blindness. In most people, IOP is tightly regulated over a lifetime by the conventional outflow tissues. However, the mechanistic contributions of age to conventional outflow dysregulation, elevated IOP and glaucoma are unknown. To address this gap in knowledge, we studied how age affects the morphology, biomechanical properties and function of conventional outflow tissues in C57BL/6 mice, which have an outflow system similar to humans. As reported in humans, we observed that IOP in mice was maintained within a tight range over their lifespan. Remarkably, despite a constellation of age‐related changes to the conventional outflow tissues that would be expected to hinder aqueous drainage and impair homeostatic function (decreased cellularity, increased pigment accumulation, increased cellular senescence and increased stiffness), outflow facility, a measure of conventional outflow tissue fluid conductivity, was stable with age. We conclude that the murine conventional outflow system has significant functional reserve in healthy eyes. However, these age‐related changes, when combined with other underlying factors, such as genetic susceptibility, are expected to increase risk for ocular hypertension and glaucoma. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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48. Aged‐vascular niche hinders osteogenesis of mesenchymal stem cells through paracrine repression of Wnt‐axis.
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Fleischhacker, Viviane, Milosic, Filip, Bricelj, Marko, Kührer, Kristina, Wahl‐Figlash, Katharina, Heimel, Patrick, Diendorfer, Andreas, Nardini, Eleonora, Fischer, Irmgard, Stangl, Herbert, Pietschmann, Peter, Hackl, Matthias, Foisner, Roland, Grillari, Johannes, Hengstschläger, Markus, and Osmanagic‐Myers, Selma
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MESENCHYMAL stem cells ,PROGERIA ,BONE growth ,FRACTURE healing ,BONE marrow ,BONE regeneration ,BONE diseases ,BONE fractures - Abstract
Age‐induced decline in osteogenic potential of bone marrow mesenchymal stem cells (BMSCs) potentiates osteoporosis and increases the risk for bone fractures. Despite epidemiology studies reporting concurrent development of vascular and bone diseases in the elderly, the underlying mechanisms for the vascular‐bone cross‐talk in aging are largely unknown. In this study, we show that accelerated endothelial aging deteriorates bone tissue through paracrine repression of Wnt‐driven‐axis in BMSCs. Here, we utilize physiologically aged mice in conjunction with our transgenic endothelial progeria mouse model (Hutchinson‐Gilford progeria syndrome; HGPS) that displays hallmarks of an aged bone marrow vascular niche. We find bone defects associated with diminished BMSC osteogenic differentiation that implicate the existence of angiocrine factors with long‐term inhibitory effects. microRNA‐transcriptomics of HGPS patient plasma combined with aged‐vascular niche analyses in progeria mice reveal abundant secretion of Wnt‐repressive microRNA‐31‐5p. Moreover, we show that inhibition of microRNA‐31‐5p as well as selective Wnt‐activator CHIR99021 boosts the osteogenic potential of BMSCs through de‐repression and activation of the Wnt‐signaling, respectively. Our results demonstrate that the vascular niche significantly contributes to osteogenesis defects in aging and pave the ground for microRNA‐based therapies of bone loss in elderly. [ABSTRACT FROM AUTHOR]
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- 2024
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49. LARP7 overexpression alleviates aortic senescence and atherosclerosis.
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Yang, Ping, Wu, Shuo, Li, Yige, Lou, Yingmei, Xiong, Junhao, Wang, Yuze, Geng, Zilong, and Zhang, Bing
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ATHEROSCLEROSIS ,GENETIC overexpression ,CELLULAR aging ,AGING ,AORTA ,MYOCARDIAL infarction ,ATHEROSCLEROTIC plaque - Abstract
Atherosclerosis, characterized by the accumulation of lipid plaques on the inner walls of arteries, is the leading cause of heart attack, stroke and severe ischemic injuries. Senescent cells have been found to accumulate within atherosclerotic lesions and contribute to the progression of atherosclerosis. In our previous study, we discovered that suppressing Larp7 accelerates senescence by inhibiting Sirt1 activity, resulting in increased atherosclerosis in high‐fat diet (HFD) fed and ApoE deficient (ApoEKO) mice. However, there has been no direct evidence demonstrating Larp7 per se could attenuate atherosclerosis. To this end, we generated a tetO‐controlled and Cre‐activated Larp7 gain‐of‐function mouse. Through RT‐PCR and western blotting, we confirmed Larp7 overexpression in the aortas of HFD‐fed ApoEKO; Larp7tetO mice. Larp7 overexpression led to increased Sirt1 activity and decreased cellular senescence signals mediated by p53/p65 in the aortas. Additionally, Larp7 overexpression reduced the presence of p16‐positive senescent cells in the aortic lesions. Furthermore, Larp7 overexpression resulted in a decrease in pro‐inflammatory macrophages and SASP factors. Consequently, Larp7 overexpression led to a reduction in the area of atherosclerotic lesions in HFD‐fed ApoEKO; Larp7tetO mice. In summary, our study provides evidence that Larp7 overexpression holds promise as an approach to inhibit cellular senescence and prevent atherosclerosis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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50. Are older people a vulnerable group? Philosophical and bioethical perspectives on ageing and vulnerability.
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Bozzaro C, Boldt J, and Schweda M
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- Aged, Bioethics, Humans, Personhood, Social Values, Aging ethics, Bioethical Issues, Personal Autonomy, Vulnerable Populations
- Abstract
The elderly are often considered a vulnerable group in public and academic bioethical debates and regulations. In this paper, we examine and challenge this assumption and its ethical implications. We begin by systematically delineating the different concepts of vulnerability commonly used in bioethics, before then examining whether these concepts can be applied to old age. We argue that old age should not, in and of itself, be used as a marker of vulnerability, since ageing is a process that can develop in a variety of different ways and is not always associated with particular experiences of vulnerability. We, therefore, turn to more fundamental phenomenological considerations in order to reconstruct from a first person perspective the intricate interconnections between the experiences of ageing and vulnerability. According to this account, ageing and old age are phenomena in which the basic anthropological vulnerability of human beings can manifest itself in an increased likelihood of harm and exploitation. Thus, we plead for a combined model of vulnerability that helps to avoid problems related to the current concepts of vulnerability. We conclude first that old age as such is not a sufficient criterion for being categorized as vulnerable in applied ethics, and second that reflections on ageing can help to develop a better understanding of the central role of vulnerability in human existence and in applied ethics., (© 2018 John Wiley & Sons Ltd.)
- Published
- 2018
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