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Telomeres shorten with age and shorter leukocyte telomere length (LTL) has been associated with various age-related diseases. Thus, LTL has been considered a biomarker of biological aging. Dyslipidemia is an established risk factor for most age-related metabolic disorders. However, little is known about the relationship between LTL and dyslipidemia. Lipidomics is a new biochemical technique that can simultaneously identify and quantify hundreds to thousands of small molecular lipid species. In a large population comprising 1843 well-characterized American Indians in the Strong Heart Family Study, we examined the lipidomic profile of biological aging assessed by LTL. Briefly, LTL was quantified by qPCR. Fasting plasma lipids were quantified by untargeted liquid chromatography–mass spectrometry. Lipids associated with LTL were identified by elastic net modeling. Of 1542 molecular lipids identified (518 known, 1024 unknown), 174 lipids (36 knowns) were significantly associated with LTL, independent of chronological age, sex, BMI, hypertension, diabetes status, smoking status, bulk HDL-C, and LDL-C. These findings suggest that altered lipid metabolism is associated with biological aging and provide novel insights that may enhance our understanding of the relationship between dyslipidemia, biological aging, and age-related diseases in American Indians. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11357-022-00638-9.

BackgroundBiological aging and particularly the deviations between biological and chronological age are better predictors of health than chronological age alone. However, the predictors of accelerated biological aging are not very well understood. The aim was to determine the role of birth outcomes, time of puberty onset, body mass index (BMI), and body fat in accelerated biological aging in the third decade of life.MethodsWe have conducted a second follow-up of the Czech part of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC-CZ) prenatal birth cohort in young adulthood (52% male; age 28–30; n = 262) to determine the role of birth outcomes, pubertal timing, BMI, and body fat on biological aging. Birth outcomes included birth weight, length, and gestational age at birth. Pubertal timing was determined by the presence of secondary sexual characteristics at the age of 11 and the age of first menarche in women. Biological age was estimated using the Klemera-Doubal Method (KDM), which applies 9-biomarker algorithm including forced expiratory volume in one second (FEV1), systolic blood pressure, glycated hemoglobin, total cholesterol, C-reactive protein, creatinine, urea nitrogen, albumin, and alkaline phosphatase. Accelerated/decelerated aging was determined as the difference between biological and chronological age (BioAGE).ResultsThe deviations between biological and chronological age in young adulthood ranged from −2.84 to 4.39 years. Accelerated biological aging was predicted by higher BMI [in both early (R2adj = 0.05) and late 20s (R2adj = 0.22)], subcutaneous (R2adj = 0.21) and visceral fat (R2adj = 0.25), puberty onset (ηp2 = 0.07), birth length (R2adj = 0.03), and the increase of BMI over the 5-year period between the two follow-ups in young adulthood (R2adj = 0.09). Single hierarchical model revealed that shorter birth length, early puberty onset, and greater levels of visceral fat were the main predictors, together explaining 21% of variance in accelerated biological aging.ConclusionOur findings provide comprehensive support of the Life History Theory, suggesting that early life adversity might trigger accelerated aging, which leads to earlier onset of puberty but decreasing fitness in adulthood, reflected by more visceral fat and higher BMI. Our findings also suggest that reduction of BMI in young adulthood slows down biological aging.

Chronic lung disease has been attributed to stem cell aging and/or exhaustion. We investigated these mechanisms using mouse and human tracheobronchial tissue‐specific stem cells (TSC). In mouse, chromatin labeling and flow cytometry demonstrated that naphthalene (NA) injury activated a subset of TSC. These activated TSC continued to proliferate after the epithelium was repaired and a clone study demonstrated that ~96% of activated TSC underwent terminal differentiation. Despite TSC attrition, epithelial repair after a second NA injury was normal. The second injury accelerated proliferation of previously activated TSC and a nucleotide‐label retention study indicated that the second injury recruited TSC that were quiescent during the first injury. These mouse studies indicate that (a) injury causes selective activation of the TSC pool; (b) activated TSC are predisposed to further proliferation; and (c) the activated state leads to terminal differentiation. In human TSC, repeated proliferation also led to terminal differentiation and depleted the TSC pool. A clone study identified long‐ and short‐lived TSC and showed that short‐lived TSC clones had significantly shorter telomeres than their long‐lived counterparts. The TSC pool was significantly depleted in dyskeratosis congenita donors, who harbor mutations in telomere biology genes. The remaining TSC had short telomeres and short lifespans. Collectively, the mouse and human studies support a model in which epithelial injury increases the biological age of the responding TSC. When applied to chronic lung disease, this model suggests that repeated injury accelerates the biological aging process resulting in abnormal repair and disease initiation., Biological aging of tracheobronchial tissue specific stem cells (TSC) and their trophic unit, the pseudostratified conducting airway epithelium. Each injury activates a subset of TSC which proliferate and undergo terminal differentiation. Thus, each injury cycle depletes the TSC pool and many injuries compromise epithelial regeneration. Over time, biological age exceeds chronological age and increases the risk of chronic lung disease.

Prior research shows that individuals who have exhibited antisocial behavior are in poorer health than their same-aged peers. A major driver of poor health is aging itself, yet research has not investigated relationships between offending trajectories and biological aging. We tested the hypothesis that individuals following a life-course persistent (LCP) antisocial trajectory show accelerated aging in midlife. Trajectories of antisocial behavior from age 7 to 26 years were studied in the Dunedin Multidisciplinary Health and Development Study, a population-representative birth cohort (N = 1037). Signs of aging were assessed at age 45 years using previously validated measures including biomarkers, clinical tests, and self-reports. First, we tested whether the association between antisocial behavior trajectories and midlife signs of faster aging represented a decline from initial childhood health. We then tested whether decline was attributable to tobacco smoking, antipsychotic medication use, debilitating illnesses in adulthood, adverse exposures in childhood (maltreatment, socioeconomic disadvantage) and adulthood (incarceration), and to childhood self-control difficulties. Study members with a history of antisocial behavior had a significantly faster pace of biological aging by midlife, and this was most evident among individuals following the LCP trajectory (β, 0.22, 95%CI, 0.14, 0.28, p ≤ 0.001). This amounted to 4.3 extra years of biological aging between ages 25–45 years for Study members following the LCP trajectory compared to low-antisocial trajectory individuals. LCP offenders also experienced more midlife difficulties with hearing (β, −0.14, 95%CI, −0.21, −0.08, p ≤ 0.001), balance (β, −0.13, 95%CI, −0.18, −0.06, p ≤ 0.001), gait speed (β, −0.18, 95%CI, −0.24, −0.10, p ≤ 0.001), and cognitive functioning (β, −0.25, 95%CI, −0.31, −0.18, p ≤ 0.001). Associations represented a decline from childhood health. Associations persisted after controlling individually for tobacco smoking, antipsychotic medication use, midlife illnesses, maltreatment, socioeconomic status, incarceration, and childhood self-control difficulties. However, the cumulative effect of these lifestyle characteristics together explained why LCP offenders have a faster Pace of Aging than their peers. While older adults typically age-out of crime, LCP offenders will likely age-into the healthcare system earlier than their chronologically same-aged peers. Preventing young people from offending is likely to have substantial benefits for health, and people engaging in a LCP trajectory of antisocial behaviors might be the most in need of health promotion programs. We offer prevention and intervention strategies to reduce the financial burden of offenders on healthcare systems and improve their wellbeing.

Biological aging is an umbrella term that refers to a complex biological process which entails the aging of cells, their organelles and DNA (Hägg & Jylhävä, 2021). Biological aging processes have been associated with a variety of diseases, including cancer and atherosclerosis (Adams & White, 2004; Dugué et al., 2018), and are a good predictor for higher morbidity and mortality rates (Perna et al., 2016). Therefore, a growing body of research is focused on potential factors affecting biological aging. Biological aging can be operationalized by different biomarkers, including telomere length and epigenetic clocks (Belsky et al., 2018; Pearce et al., 2022). Telomeres are repetitive TTAGGG sequences at the end of chromosomes that protect the chromosomes from shortening during cell division. Telomeres shorten throughout the lifespan, and accelerated telomere shortening is an index of accelerated biological aging (Tempaku et al., 2015; Vaiserman & Krasnienkov, 2021). Furthermore, the epigenetic clock concerns DNA methylation levels, namely the accumulation of methyl groups to DNA molecules, and is an estimator of chronical age (Chen et al., 2016; Jylhävä et al., 2017). These clocks capture methylation of certain sets of CpG sites in the DNA, and methylation levels correlate with age. Accordingly, the biological age of the cells can be calculated in years (Chen et al., 2016; Horvath et al., 2012; McEwen et al., 2020). It has been found that, besides genetic factors (Gibson et al., 2019), also environmental factors, such as smoking and diet, are associated with both of the previous biomarkers of accelerated biological aging (Gao et al., 2016; Horvath et al., 2014; Huang et al., 2019; Vaiserman & Krasnienkov, 2021). Accelerated biological aging in terms of accelerated telomere attrition and advanced epigenetic age has also been associated with sleeping problems in adults (Carskadon et al., 2019; Carroll & Prather, 2021; Cribbet et al., 2014; Gao et al., 2022; James et al., 2017; Jin et al., 2022). Sleep is a complex behavioral and homeostatically regulated state of all mammals (Zielinski et al., 2016). Sleep has many vital functions, including development, modulation of immune responses, memory consolidation and endocrine functions (Krueger et al., 2016; Zielinski et al., 2016). Previous research has demonstrated associations between poor quality of sleep, shorter sleep duration, and delayed sleep onset with shortened telomere lengths (Cribbet et al., 2014; Wynchank et al., 2019). Additionally, reduced sleep duration and poor sleep quality have also been linked to the acceleration of the epigenetic clock (Carskadon et al., 2019; Gao et al., 2022) This association between sleep and accelerated biological aging was not only observed in adults. James and colleagues (2017) found an association of shorter telomeres with shorter sleep durations in nine-year-old children, indicating that the relationship between biological aging and sleep already emerges early in development (James et al., 2017). However, to our knowledge, this is the only study that has looked at children’s sleep in relation to markers for biological aging. Therefore, to date, there is a lack of research on the association of sleep quality with biological aging in children. Additionally, the previously mentioned study on this association in children was cross-sectional, hence the directionality of the relationship between biological aging and sleep quality in children remains unclear. On the one hand, previous studies in adults have largely assumed that more sleeping problems cause alterations in neuro-chemical processes, which, in turn, cause accelerated aging. But on the other hand, studies on the elderly population suggest that accelerated aging can cause significant alterations in the sleep stages and in the quantity and quality of sleep (Tempaku et al., 2015), indicating that aging could also bring about sleep changes. Accordingly, Carrol and Prather (2021) suggest that there is also a possibility that accelerated biological aging causes alterations in brain areas that regulate sleep states, hereby causing sleep difficulties (Carroll & Prather, 2021). Since previous research on the association of sleep and biological aging in children was solely cross-sectional, the directionality of the association remains to be assessed. In the current study we assess the association of sleep with accelerated biological aging in children bi-directionally between chronological ages 6 years (T1) and 10 years (T2). As telomere length and epigenetic clocks have been shown to capture different biological aging processes (Belsky et al., 2018; Pearce et al., 2022), both will be used in this study to measure biological aging. In previous studies, the Pediatric-Buccal-Epigenetic (PedBE) clock has been reported to be the most reliable epigenetic clock for pediatrics (McEwen et al., 2020), and will hence be used in the current study. In this study, we will assess the following goals: 1) Our first goal is to assess cross-sectional associations at T1 and T2 between our biomarkers of biological aging (telomere length and PedBE clock) with child sleeping problems. 2) Our second goal is to determine whether sleeping problems at T1 forecasts biological aging, defined as a) telomere length at T2; b) telomere erosion between T1 – and T2; c) PedBE clock at T2. 3) Our third goal is to determine whether our biomarkers of biological aging (a, b & c) predict sleeping problems at T2. a) telomere length; b) telomere erosion from T1 to T2; c) PedBE clock at T1. 4) Lastly, we will assess the directionality between sleeping problems and biological aging by comparing the explained variance between question 2 and 3. Note that we do not include the change in PedBE from T1 to T2, as the PedBE clock already incorporates the difference between biological aging and chronological aging as an age acceleration. Given that telomere length and/or erosion varies by sex (Barrett & Richardson, 2011), z-score body mass index index (zBMI; Clemente et al., 2019; Gielen et al., 2018), and maternal education (Broer et al., 2013), we will statistically control for these aspects in our analyses. This will be done by using child sex determined at birth, child zBMI at T2 and maternal education defined as the highest level of education completed when assessed at T2 (Beijers, Hartman, et al., 2020; Shalev et al., 2013).

Chronological age (i.e., time since birth) is known to be a major predictor for lower cognitive performance and decline. Although the passing of time is easily measured and convenient to collect, chronological age alone cannot explain why some 60-year-olds are at an increased risk for cognitive decline, whereas others escape major cognitive deficits until extreme ages. Thus, chronological age is of limited utility for understanding mechanisms underlying cognitive decline. Fortunately, epigenetic clocks, with which an individual’s biological age can be quantified by levels of DNA methylation (DNAm) at key sites in the genome, have been empirically developed. These clocks provide the opportunity to assess accelerated aging, in which an individual’s biological age is greater than their chronological age. As such, accelerated biological aging presents a unique opportunity as a more robust predictor for cognitive decline. In this project, we take advantage of an existing dataset that contains DNAm data and longitudinal cognitive assessments for processing speed and working memory, to address the questions such as - why are two 60-year-olds so different in terms of their cognitive function? Specifically, we use individuals’ biological age from methylation-based epigenetic clocks to predict individual differences in cognitive performance in daily life.

Background Chronological age (CA) is a predictor of adverse coronavirus disease 2019 (COVID-19) outcomes; however, CA alone does not capture individual responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we evaluated the influence of aging metrics PhenoAge and PhenoAgeAccel to predict adverse COVID-19 outcomes. Furthermore, we sought to model adaptive metabolic and inflammatory responses to severe SARS-CoV-2 infection using individual PhenoAge components. Method In this retrospective cohort study, we assessed cases admitted to a COVID-19 reference center in Mexico City. PhenoAge and PhenoAgeAccel were estimated using laboratory values at admission. Cox proportional hazards models were fitted to estimate risk for COVID-19 lethality and adverse outcomes (intensive care unit admission, intubation, or death). To explore reproducible patterns which model adaptive responses to SARS-CoV-2 infection, we used k-means clustering using PhenoAge components. Results We included 1068 subjects of whom 222 presented critical illness and 218 died. PhenoAge was a better predictor of adverse outcomes and lethality compared to CA and SpO2 and its predictive capacity was sustained for all age groups. Patients with responses associated to PhenoAgeAccel >0 had higher risk of death and critical illness compared to those with lower values (log-rank p < .001). Using unsupervised clustering, we identified 4 adaptive responses to SARS-CoV-2 infection: (i) inflammaging associated with CA, (ii) metabolic dysfunction associated with cardiometabolic comorbidities, (iii) unfavorable hematological response, and (iv) response associated with favorable outcomes. Conclusions Adaptive responses related to accelerated aging metrics are linked to adverse COVID-19 outcomes and have unique and distinguishable features. PhenoAge is a better predictor of adverse outcomes compared to CA.

BackgroundSeveral studies have evaluated whether depressed persons have older appearing brains than their nondepressed peers. However, the estimated neuroimaging-derived “brain age gap” has varied from study to study, likely driven by differences in training and testing sample (size), age range, and used modality/features. To validate our previously developed ENIGMA brain age model and the identified brain age gap, we aim to replicate the presence and effect size estimate previously found in the largest study in depression to date (N=2,126 controls & N=2,675 cases; +1.08 years [SE 0.22], Cohen’s d=0.14, 95% CI: 0.08-0.20), in independent cohorts that were not part of the original study.MethodsA previously trained brain age model (www.photon-ai.com/enigma_brainage) based on 77 FreeSurfer brain regions of interest was used to obtain unbiased brain age predictions in 751 controls and 766 persons with depression (18-75 years) from 13 new cohorts collected from 20 different scanners.ResultsOur ENIGMA MDD brain age model generalized reasonably well to controls from the new cohorts (predicted age vs. age: r = 0.73, R2=0.47, MAE=7.50 years), although the performance varied from cohort to cohort. In these new cohorts, on average, depressed persons showed a significantly higher brain age gap of +1 year (SE 0.35) (Cohen’s d□=□□.15, 95% CI: 0.05–0.25) compared with controls, highly similar to our previous finding.ConclusionsThis study further validates our previously developed ENIGMA brain age algorithm. Importantly, we replicated the brain age gap in depression with a comparable effect size. Thus, two large-scale independent mega-analyses across in total 32 cohorts and >3,400 patients and >2,800 controls worldwide show reliable but subtle effects of brain aging in adult depression.

Conduct disorder is a psychological disorder primarily diagnosed to adolescents and children with behavioral issues. Conduct disorder may present as the failure to follow rules outlined by a figure of authority, destruction of property, and aggression. Previous studies have suggested a correlation between the experience of childhood trauma and the development of conduct disorder (Bassarath, 2001). Further study has established a negative correlation between early life stress and telomere length, which is considered a measurement of biological age (Epel et al., 2004). Given these relationships, I will examine the relationship between telomere length and symptoms of conduct disorder present in data collected from a community sample of adolescents ages 9-14 years. 1. Bassarath L. Conduct disorder: a biopsychosocial review. Can J Psychiatry. 2001 Sep;46(7):609-16. doi: 10.1177/070674370104600704. PMID: 11582821. 2. Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, Cawthon RM. Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17312-5. doi: 10.1073/pnas.0407162101. Epub 2004 Dec 1. PMID: 15574496; PMCID: PMC534658.

Purpose This study aimed to perform a validity and reliability study of the Turkish version of the Aging Anxiety Scale for Middle-Aged Women. Design and Methods This methodological study was conducted with 262 women aged between 40 and 59 years. Findings While language, content and construct validity analyses were performed at the validity phase of the scale, internal consistency and stability over time analyses were performed at the reliability stage. Factor analyses were performed for the construct validity, and it was determined that the items of the scale were classified under four factors; this was consistent with the original form. The Cronbach's alpha reliability was 0.962 for the overall scale and ranged between 0.836 and 0.949 for the four subdimensions. Practice Implications The study determined that the Turkish adaptation of the scale is a valid and reliable measuring instrument., Ege University Scientific Research Projects Program [TGA-202021735], Ege University Scientific Research Projects Program, Grant/Award Number: TGA-202021735

Flor yeast velum is a biofilm formed by certain yeast strains that distinguishes biologically aged wines such as Sherry wine from southern Spain from others. AlthoughSaccharomyces cerevisiaeis the most common species, 5.8 S-internal transcribed spacer (ITS) restriction fragment length polymorphism analyses have revealed the existence of non-Saccharomycesspecies. In order to uncover the flor microbiota diversity at a species level, we used ITS (internal transcribed spacer 1)-metabarcoding and matrix-assisted laser desorption/Ionization time of flight mass spectrometry techniques. Further, to enhance identification effectiveness, we performed an additional incubation stage in 1:1 wine:yeast extract peptone dextrose (YPD) before identification. Six species were identified:S. cerevisiae,Pichia manshurica,Pichia membranifaciens,Wickerhamomyces anomalus,Candida guillermondii, andTrichosporon asahii, two of which were discovered for the first time (C. guillermondiiandTrichosporon ashaii) in Sherry wines. We analyzed wines where non-Saccharomycesyeasts were present or absent to see any potential link between the microbiota and the chemical profile. Only 2 significant volatile chemicals (out of 13 quantified), ethanol and ethyl lactate, and 2 enological parameters (out of 6 quantified), such as pH and titratable acidity, were found to differ in long-aged wines. Although results show a low impact where the non-Saccharomycesyeasts are present, these yeasts isolated from harsh environments (high ethanol and low nutrient availability) could have a potential industrial interest in fields such as food microbiology and biofuel production.

Biological age (BA) is the hypothetical underlying age of an organism and has been proposed as a more powerful predictor of health than chronological age (CA). The difference between BA and CA (Δage) reflects the rate of biological aging, with lower values indicating slowed-down aging. We sought to compare the relationship of four a priori-defined dietary patterns, including a traditional Mediterranean diet (MD) and three non-Mediterranean diets, with biological aging (Δage) among Italian adults. We also examined distinctive nutritional traits of these diets as potential mediators of such associations.Cross-sectional analysis on a sub-cohort of 4510 subjects (aged ≥35 y; 52.0% women) from the Moli-sani Study (enrolment, 2005-2010). Food intake was recorded by a 188-item semi-quantitative food-frequency questionnaire. A Mediterranean diet score (MDS) was used as exposure and compared with non-Mediterranean dietary patterns, i.e. DASH (Dietary Approaches to Stop Hypertension), Palaeolithic and the Nordic diets. A Deep Neural Network based on 36 blood biomarkers was used to compute BA and the resulting Δage (BA-CA), which was tested as outcome in multivariable linear regressions adjusted for clinical factors, lifestyles and sociodemographic factors.In a multivariable-adjusted model, 1 standard deviation increase in the MDS was inversely associated with Δage (β = -0.23; 95%CI -0.40, -0.07), and similar findings were observed with the DASH diet (β = -0.17; 95%CI -0.33, -0.01). High dietary polyphenol content explained 29.8% (p = 0.04) and 65.8% (p = 0.02) of these associations, respectively, while other nutritional factors analysed (e.g. dietary fibre) were unlikely to be on the pathway. No significant associations were found with either the Palaeolithic or the Nordic diets.Increasing adherence to either the traditional MD or the DASH diet was associated with delayed biological aging, possibly through their high polyphenol content.

International audience; Aging is the most important risk factor for the onset of several chronic diseases and functional decline. Understanding the interplays between biological aging and the biology of diseases and functional loss as well as integrating a function-centered approach to the care pathway of older adults are crucial steps towards the elaboration of preventive strategies (both pharmacological and non-pharmacological) against the onset and severity of burdensome chronic conditions during aging. In order to tackle these two crucial challenges, ie, how both the manipulation of biological aging and the implementation of a function-centered care pathway (the Integrated Care for Older People (ICOPE) model of the World Health Organization) may contribute to the trajectories of healthy aging, a new initiative on Gerosciences was built: the INSPIRE research program. The present article describes the scientific background on which the foundations of the INSPIRE program have been constructed and provides the general lines of this initiative that involves researchers from basic and translational science, clinical gerontology, geriatrics and primary care, and public health.

Background:Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously, we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al., 2020). Here, we report a next-generation DNA-methylation biomarker of Pace of Aging, DunedinPACE (for Pace of Aging Calculated from the Epigenome).Methods:We used data from the Dunedin Study 1972–1973 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named DunedinPACE, in five additional datasets.Results:DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of incident morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge.Conclusions:DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience.Funding:This research was supported by US-National Institute on Aging grants AG032282, AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1.

Estimators of biological age (BA) - defined as the hypothetical underlying age of an organism - have attracted more and more attention in the last years, especially after the advent of new algorithms based on machine learning and genetic markers. While different aging clocks reportedly predict mortality in the general population, very little is known on their overlap. Here we review the evidence reported so far to support the existence of a partial overlap among different BA acceleration estimators, both from an epidemiological and a genetic perspective. On the epidemiological side, we review evidence supporting shared and independent influence on mortality risk of different aging clocks - including telomere length, brain, blood and epigenetic aging - and provide an overview of how an important exposure like diet may affect the different aging systems. On the genetic side, we apply linkage disequilibrium score regression analyses to support the existence of partly shared genomic overlap among these aging clocks. Through multivariate analysis of published genetic associations with these clocks, we also identified the most associated variants, genes, and pathways, which may affect common mechanisms underlying biological aging of different systems within the body. Based on our analyses, the most implicated pathways were involved in inflammation, lipid and carbohydrate metabolism, suggesting them as potential molecular targets for future anti-aging interventions. Overall, this review is meant as a contribution to the knowledge on the overlap of aging clocks, trying to clarify their shared biological basis and epidemiological implications.

Disruption of age-related processes seems to play a relevant role in health effects related to night shift (NS) work. We aim to verify whether NS work can influence biological age (BA), estimated through Zbieć-Piekarska’s epigenetic signature, based on methylation of five CpG sites in ELOVL2, C1orf132/MIR29B2C, TRIM59, KLF14, and FHL2. Forty-six female nurses working in NS were matched by age and length of employment with 51 female colleagues not working in NS. Each subject filled in a questionnaire (including the Effort Reward Imbalance (ERI) index to assess job stress) and gave a blood sample. Age acceleration (AA) was estimated by regressing BA on chronological age and taking the residuals. Multivariate linear regression models were applied. BA was not associated with NS. However, we did observe an increase in AA per each year in NS in subjects with overweight/obesity (β = 0.46, 95% CI: 0.05; 0.87, p = 0.03), experiencing work-related stress (β = 0.58, 95% CI: 0.10; 1.06, p = 0.018), or both (β = 0.66, 95% CI: 0.03; 1.29, p = 0.041). Although based on a small sample size, our findings suggest an increased BA only among hypersusceptible subjects and is worth further investigation, also in light of recent results suggesting a higher breast cancer risk in women with increased AA.

Aging is a complex biological process characterized by hallmark features accumulating over the life course, shaping the individual's aging trajectory and subsequent disease risks. There is substantial individual variability in the aging process between men and women. In general, women live longer than men, consistent with lower biological ages as assessed by molecular biomarkers, but there is a paradox. Women are frailer and have worse health at the end of life, while men still perform better in physical function examinations. Moreover, many age-related diseases show sex-specific patterns. In this review, we aim to summarize the current knowledge on sexual dimorphism in human studies, with support from animal research, on biological aging and illnesses. We also attempt to place it in the context of the theories of aging, as well as discuss the explanations for the sex differences, for example, the sex-chromosome linked mechanisms and hormonally driven differences.

Aging clocks dissociate biological from chronological age. The estimation of biological age is important for identifying gerontogenes and assessing environmental, nutritional, or therapeutic impacts on the aging process. Recently, methylation markers were shown to allow estimation of biological age based on age‐dependent somatic epigenetic alterations. However, DNA methylation is absent in some species such as Caenorhabditis elegans and it remains unclear whether and how the epigenetic clocks affect gene expression. Aging clocks based on transcriptomes have suffered from considerable variation in the data and relatively low accuracy. Here, we devised an approach that uses temporal scaling and binarization of C. elegans transcriptomes to define a gene set that predicts biological age with an accuracy that is close to the theoretical limit. Our model accurately predicts the longevity effects of diverse strains, treatments, and conditions. The involved genes support a role of specific transcription factors as well as innate immunity and neuronal signaling in the regulation of the aging process. We show that this binarized transcriptomic aging (BiT age) clock can also be applied to human age prediction with high accuracy. The BiT age clock could therefore find wide application in genetic, nutritional, environmental, and therapeutic interventions in the aging process., Using Caenorhabditis elegans RNA seq and lifespan datasets we developed a binarized transcriptomic aging (BiT age) clock with a precision close to the theoretical limit of accuracy that can also be applied to humans. The BiT age clock allows quantification of pro‐ and anti‐aging effects of genetic, nutritional, environmental and pharmacological interventions in the aging process.

Biological clocks have been developed at different molecular levels and were found to be more advanced in the presence of somatic illness and mental disorders. However, it is unclear whether different biological clocks reflect similar aging processes and determinants. In ~3000 subjects, we examined whether five biological clocks (telomere length, epigenetic, transcriptomic, proteomic, and metabolomic clocks) were interrelated and associated to somatic and mental health determinants. Correlations between biological aging indicators were small (all r < 0.2), indicating little overlap. The most consistent associations of advanced biological aging were found for male sex, higher body mass index (BMI), metabolic syndrome, smoking, and depression. As compared to the individual clocks, a composite index of all five clocks showed most pronounced associations with health determinants. The large effect sizes of the composite index and the low correlation between biological aging indicators suggest that one’s biological age is best reflected by combining aging measures from multiple cellular levels.

Objective Studies of multiple species have found that adverse early life experiences, including childhood trauma and maternal separation, can result in accelerated telomere shortening. The objective of this study was to determine if premature separation from the mother affected telomere length in domestic kittens (Felis catus). Subjects were 42 orphaned kittens and 10 mother-reared kittens from local animal rescue groups and shelters. DNA was extracted from whole blood collected from kittens at approximately 1 week and 2 months of age. Telomere length was assessed by qPCR (quantitative polymerase chain reaction) from a total of 86 samples and expressed as a ratio of telomere PCR relative to a single copy gene PCR (T/S). Results A generalized linear mixed model found there were no detectable differences in telomere length based on survival (F1, 76.2 = 3.35, p = 0.07), orphan status (F1, 56.5 = 0.44, p = 0.51), time point (F1, 43.5 = 0.19, p = 0.67), or the interaction between orphan status and time (F1, 43.5 = 0.86, p = 0.36). Although in other species telomere shortening is commonly associated with aging, even early in life, we did not find evidence for telomere shortening by two months of age. Our results suggest that the experience of early maternal separation in domestic cats who are subsequently hand-reared by humans does not accelerate telomere shortening compared to mother-reared kittens, at least in the first few months of life.

Telomeres are protective cap structures at the end of chromosomes that are essential for maintaining genomic stability. Accelerated telomere shortening is related to premature cellular senescence. Shortened telomere lengths (TL) have been implicated in the pathogenesis of various chronic immune-mediated and neurological diseases. We aimed to systematically review the current literature on the association of TL as a measure of biological age and multiple sclerosis (MS). A comprehensive literature search was conducted to identify original studies that presented data on TL in samples from persons with MS. Quantitative and qualitative information was extracted from the articles to summarize and compare the studies. A total of 51 articles were screened, and 7 of them were included in this review. In 6 studies, average TL were analyzed in peripheral blood cells, whereas in one study, bone marrow-derived cells were used. Four of the studies reported significantly shorter leukocyte TL in at least one MS subtype in comparison to healthy controls (p=0.003 in meta-analysis). Shorter telomeres in patients with MS were found to be associated, independently of age, with greater disability, lower brain volume, increased relapse rate and more rapid conversion from relapsing to progressive MS. However, it remains unclear how telomere attrition in MS may be linked to oxidative stress, inflammation and age-related disease processes. Despite few studies in this field, there is substantial evidence on the association of TL and MS. Variability in TL appears to reflect heterogeneity in clinical presentation and course. Further investigations in large and well-characterized cohorts are warranted. More detailed studies on TL of individual chromosomes in specific cell types may help to gain new insights into the pathomechanisms of MS.

BackgroundFurther knowledge on modifiable aging risk factors is required to mitigate the increasing burden of age-related diseases in a rapidly growing global demographic of elderly individuals. We explored the effect of everyday exposure to polycyclic aromatic hydrocarbons (PAHs), which are fundamental constituents of air pollution, on cellular biological aging. This was determined via the analysis of leukocyte telomere length (LTL), mitochondrial DNA copy number (LmtDNAcn), and by the formation of anti-benzo[a]pyrene diolepoxide (B[a]PDE–DNA) adducts.MethodsThe study population consisted of 585 individuals living in North-East Italy. PAH exposure (diet, indoor activities, outdoor activities, traffic, and residential exposure) and smoking behavior were assessed by questionnaire and anti-B[a]PDE–DNA by high-performance-liquid-chromatography. LTL, LmtDNAcn and genetic polymorphisms [glutathione S-transferase M1 and T1 (GSTM1; GSTT1)] were measured by polymerase chain reaction. Structural equation modelling analysis evaluated these complex relationships.ResultsAnti-B[a]PDE–DNA enhanced with PAH exposure (p = 0.005) and active smoking (p = 0.0001), whereas decreased with detoxifying GSTM1 (p = 0.021) and in females (p = 0.0001). Subsequently, LTL and LmtDNAcn reduced with anti-B[a]PDE–DNA (p = 0.028 andp = 0.018), particularly in males (p = 0.006 andp = 0.0001). Only LTL shortened with age (p = 0.001) while elongated with active smoking (p = 0.0001). Besides this, the most significant determinants of PAH exposure that raised anti-B[a]PDE–DNA were indoor and diet (p = 0.0001), the least was outdoor (p = 0.003).ConclusionNew findings stemming from our study suggest that certain preventable everyday life exposures to PAHs reduce LTL and LmtDNAcn. In particular, the clear association with indoor activities, diet, and gender opens new perspectives for tailored preventive measures in age-related diseases.CapsuleEveryday life exposure to polycyclic aromatic hydrocarbons reduces leukocyte telomere length and mitochondrial DNA copy number through anti-B[a]PDE-DNA adduct formation.

Objective Studies of multiple species have found that adverse early life experiences, including childhood trauma and maternal separation, can result in accelerated telomere shortening. The objective of this study was to determine if premature separation from the mother affected telomere length in domestic kittens (Felis catus). Subjects were 42 orphaned kittens and 10 mother-reared kittens from local animal rescue groups and shelters. DNA was extracted from whole blood collected from kittens at approximately 1 week and 2 months of age. Telomere length was assessed by qPCR (quantitative polymerase chain reaction) from a total of 86 samples and expressed as a ratio of telomere PCR relative to a single copy gene PCR (T/S). Results A generalized linear mixed model found there were no detectable differences in telomere length based on survival (F1, 76.2 = 3.35, p = 0.07), orphan status (F1, 56.5 = 0.44, p = 0.51), time point (F1, 43.5 = 0.19, p = 0.67), or the interaction between orphan status and time (F1, 43.5 = 0.86, p = 0.36). Although in other species telomere shortening is commonly associated with aging, even early in life, we did not find evidence for telomere shortening by two months of age. Our results suggest that the experience of early maternal separation in domestic cats who are subsequently hand-reared by humans does not accelerate telomere shortening compared to mother-reared kittens, at least in the first few months of life.

Chronic stress can accelerate biological aging, offering one mechanism through which stress may increase age-related disease risk. Chronic activation of the sympathoadrenal system increases cellular energy production, resulting in cell stress that can initiate cellular senescence, a permanent state of cell growth arrest. Our previous research linked psychosocial stress with increased expression of senescence marker p16INK4a; however, less is known about the role of protective psychosocial factors in biological aging. We examined relationship closeness (perceived interconnectedness with one’s spouse) as a protective buffer of the effects of stress on expression of the p16INK4a-encoding gene (CDKN2A) and transcription control pathways activated under cell stress. Seventy parents (Mage=43.2) completed interview-based and questionnaire measures of psychosocial stress and relationship closeness. Blood samples assessed CDKN2A expression and inferred activity of a priori-selected transcription factors Nrf2 and heat shock factors (HSFs) via genome-wide transcriptome profiling. Random intercept models adjusting for age, sex, and ethnicity/race revealed that perceived stress was associated with elevated CDKN2A expression for parents with low but not high closeness. Secondary bioinformatics analyses linked the interaction of perceived stress and relationship closeness to Nrf2 and HSF-1 activity. Findings identify relationship closeness as a protective factor that may buffer the impact of stress on cellular stress and senescence pathways.

Background Prior studies in humans have suggested that telomere shortening may be accelerated by infection, but research on multiple pathogens and use of large population-based study samples has been limited. We estimated cross-sectional associations between seropositivity to five persistent pathogens (Herpes Simplex Virus Type-1 (HSV-1), Herpes Simplex Virus Type-2 (HSV-2), cytomegalovirus (CMV), Helicobacter pylori (H.pylori), and Hepatitis B) as well as total pathogen burden and leukocyte telomere length. Data were derived from the National Health and Nutrition Examination Survey (1999–2000) for individuals 20–49 years of age, N = 1708. We analyzed the influence of each pathogen separately, a pathogen count score and a latent class model of pathogen burden on log telomere length using linear regression models, adjusted for covariates. Results Individuals in a latent pathogen burden class characterized by high probabilities of infection with HSV-1, CMV, and H. pylori, had significantly decreased log telomere length (− 0.30 [95% CI: − 0.36, − 0.24]) compared to those in a latent class characterized by low probabilities of all five infections. There were limited significant associations using other pathogen measures. Conclusions These results suggest that infection with specific combinations of pathogens may be one mechanism contributing to accelerated cellular senescence with possible origins early in the life course.

BACKGROUND: Environmental and population characteristics seem to influence the variation in cutoff points of the Short Physical Performance Battery (SPPB) for diagnosing frailty syndrome among older adults. OBJECTIVE: To verify the validity of the SPPB for screening for frailty syndrome among older adults in the Amazonian context. DESIGN AND SETTING: Cross-sectional population-based study on older adults in the urban area of Coari (AM), Brazil. METHODS: In total, 264 older adults (60 years of age or over) were included. Frailty syndrome was defined using the Fried phenotype criteria. The SPPB cutoff points were compared in relation to frailty and validity measurements were calculated for the test. RESULTS: A strong association between poor physical performance and frailty was identified (P < 0.001). The cutoff point of 6 demonstrated the best validity measurements for frailty in the sample studied (sensitivity: 0.28; specificity: 0.94; accuracy: 0.88; area under the receiver operating characteristic curve, AUC-ROC: 0.61; likelihood ratio, LR+: 4.44; LR-: 0.77; prevalence: 8.3%; post-test probability, PTP+: 0.32; PTP-: 0.07), with emphasis on high specificity and the positive likelihood ratio value. CONCLUSION: The SPPB was shown to be useful for screening frail older adults in the Amazon region. The score of 6 demonstrated the best cutoff point for this population. This could be used in healthcare services for diagnostic screening for frailty among older people within the Amazonian context.

The underlying premise of current theories of cognitive decline with age tend to be primarily cognitive or biological explanations, with relatively few theories adequately integrating both aspects. Though literature has also emphasized the importance of several factors that contribute to cognitive aging including: (a) decline in sensory abilities; (b) the effect of motor speed on paper-pencil measures of cognitive speed; (c) the impact of level of education and physical activity; and (d) molecular biological changes that occur with age, these factors have seldom been implicated into any single theoretical model of cognitive aging. Indeed, such an integrated bio-cognitive model of aging has the potential to provide a more comprehensive understanding of attention, perception, learning, and memory across the lifespan. Thus, the aim of this review was to critically evaluate common theories of age-related cognitive decline and highlight the need for a more comprehensive systems neuroscience approach to cognitive aging.

Biological aging is the gradual, progressive decline in system integrity that occurs with advancing chronological age, causing morbidity and disability. Measurements of the pace of aging are needed as surrogate endpoints in trials of therapies designed to prevent disease by slowing biological aging. We report a blood-DNA-methylation measure that is sensitive to variation in pace of biological aging among individuals born the same year. We first modeled change-over-time in 18 biomarkers tracking organ-system integrity across 12 years of follow-up in n = 954 members of the Dunedin Study born in 1972–1973. Rates of change in each biomarker over ages 26–38 years were composited to form a measure of aging-related decline, termed Pace-of-Aging. Elastic-net regression was used to develop a DNA-methylation predictor of Pace-of-Aging, called DunedinPoAm for Dunedin(P)ace(o)f(A)ging(m)ethylation. Validation analysis in cohort studies and the CALERIE trial provide proof-of-principle for DunedinPoAm as a single-time-point measure of a person’s pace of biological aging., eLife digest People’s bodies age at different rates. Age-related biological changes that increase the risk of disease and disability progress rapidly in some people. In others, these processes occur at a slower pace, allowing those individuals to live longer, healthier lives. This observation has led scientists to try to develop therapies that slow aging. The hope is that such treatments could prevent or delay diseases like heart disease or dementia, for which older age is the leading risk factor. Studies in animals have identified treatments that extend the creatures’ lives and slow age-related disease. But testing these treatments in humans is challenging. Our lives are much longer than the worms, flies or mice used in the experiments. Scientists would have to follow human study participants for decades to detect delays in disease onset or an extension of their lives. An alternative approach is to try to develop a test that measures the pace of aging, or essentially “a speedometer for aging”. This would allow scientists to more quickly determine if treatments slow the aging process. Now, Belsky et al. show a blood test designed to measure the pace of aging predicts which people are at increased risk of poor health, chronic disease and an earlier death. First, data about chemical changes to an individual’s DNA, called DNA methylation, were analyzed from white blood cell samples collected from 954 people in a long-term health study known as “The Dunedin Study”. Using the data, Belsky et al. then developed an algorithm – named “DunedinPoAm” – that identified people with an accelerated or slowed pace of aging based on a single blood test. Next, they used the algorithm on samples from participants in three other long-term studies. This verified that those people the algorithm identified as aging faster had a greater risk of poor health, developing chronic diseases or dying earlier. Similarly, those identified as aging more slowly performed better on tests of balance, strength, walking speed and mental ability, and they also looked younger to trained raters. Additionally, Belsky et al. used the test on participants in a randomized trial testing whether restricting calories had potential to extend healthy lifespan. The results suggested that the calorie restriction could counter the effects of an accelerated pace of aging. The test developed by Belsky et al. may provide an alternate way of measuring whether age-slowing treatments work. This would allow faster testing of treatments that can extend the healthy lifespan of humans. The test may also help identify individuals with accelerated aging. This might help public health officials test whether policies or programs can help people lead longer, healthier lives.

Background Transdiagnostic processes confer risk for multiple types of psychopathology and explain the co-occurrence of different disorders. For this reason, transdiagnostic processes provide ideal targets for early intervention and treatment. Childhood trauma exposure is associated with elevated risk for virtually all commonly occurring forms of psychopathology. We articulate a transdiagnostic model of the developmental mechanisms that explain the strong links between childhood trauma and psychopathology as well as protective factors that promote resilience against multiple forms of psychopathology. Main body We present a model of transdiagnostic mechanisms spanning three broad domains: social information processing, emotional processing, and accelerated biological aging. Changes in social information processing that prioritize threat-related information—such as heightened perceptual sensitivity to threat, misclassification of negative and neutral emotions as anger, and attention biases towards threat-related cues—have been consistently observed in children who have experienced trauma. Patterns of emotional processing common in children exposed to trauma include elevated emotional reactivity to threat-related stimuli, low emotional awareness, and difficulties with emotional learning and emotion regulation. More recently, a pattern of accelerated aging across multiple biological metrics, including pubertal development and cellular aging, has been found in trauma-exposed children. Although these changes in social information processing, emotional responding, and the pace of biological aging reflect developmental adaptations that may promote safety and provide other benefits for children raised in dangerous environments, they have been consistently associated with the emergence of multiple forms of internalizing and externalizing psychopathology and explain the link between childhood trauma exposure and transdiagnostic psychopathology. Children with higher levels of social support, particularly from caregivers, are less likely to develop psychopathology following trauma exposure. Caregiver buffering of threat-related processing may be one mechanism explaining this protective effect. Conclusion Childhood trauma exposure is a powerful transdiagnostic risk factor associated with elevated risk for multiple forms of psychopathology across development. Changes in threat-related social and emotional processing and accelerated biological aging serve as transdiagnostic mechanisms linking childhood trauma with psychopathology. These transdiagnostic mechanisms represent critical targets for early interventions aimed at preventing the emergence of psychopathology in children who have experienced trauma.

Epigenetic clocks, developed using DNA methylation data, have been widely used to quantify biological aging in multiple tissues/cells. However, many existing epigenetic clocks are weakly correlated with each other, suggesting they may capture different biological processes. We utilize multi‐omics data from diverse human tissue/cells to identify shared features across eleven existing epigenetic clocks. Despite the striking lack of overlap in CpGs, multi‐omics analysis suggested five clocks (Horvath1, Horvath2, Levine, Hannum, and Lin) share transcriptional associations conserved across purified CD14+ monocytes and dorsolateral prefrontal cortex. The pathways enriched in the shared transcriptional association suggested links between epigenetic aging and metabolism, immunity, and autophagy. Results from in vitro experiments showed that two clocks (Levine and Lin) were accelerated in accordance with two hallmarks of aging—cellular senescence and mitochondrial dysfunction. Finally, using multi‐tissue data to deconstruct the epigenetic clock signals, we developed a meta‐clock that demonstrated improved prediction for mortality and robustly related to hallmarks of aging in vitro than single clocks., We compared 11 existing epigenetic clocks on the basis of their functional characteristics, transcriptional associations, and ability to capture hallmarks of aging. We then decomposed their signals and recombined them into a “meta‐clock.” This meta‐clock showed stronger prediction of all‐cause mortality than any one epigenetic clock and was able to distinguish tumor from normal tissue and capture epigenetic changes in two types of senescence (replicative and oncogene induced).

Normal aging is associated with changes in volumetric indices of brain atrophy. A quantitative understanding of age-related brain changes can shed light on successful aging. To investigate the effect of age on global and regional brain volumes and cortical thickness, 3514 magnetic resonance imaging scans were analyzed using automated brain segmentation and parcellation methods in elderly healthy individuals (69–88 years of age). The machine learning algorithm extreme gradient boosting (XGBoost) achieved a mean absolute error of 2 years in predicting the age of new subjects. Feature importance analysis showed that the brain-to-intracranial-volume ratio is the most important feature in predicting age, followed by the hippocampi volumes. The cortical thickness in temporal and parietal lobes showed a superior predictive value than frontal and occipital lobes. Insights from this approach that integrate model prediction and interpretation may help to shorten the current explanatory gap between chronological age and biological brain age.

Review The purpose of this review is to provide a general description of ancient winemaking techniques and wine styles that were most lauded in antiquity, in support of their revival and dissemination today. From the first fully excavated winery, dating from the late fifth to the early fourth millennium BC, the gentle crushing of grapes by foot and the probable absence of maceration indicate that most wines were made with the aim of reducing astringency. The oxidative nature of winemaking would have resulted in rapid browning, so that wines made from red grapes would have had a similar color to those made from white grapes after being aged in clay vats for several years. The difficulty in preventing the wine surface contact with the air would have resulted in biological ageing under the yeast pellicle being a common occurrence. This phenomenon was not considered a flaw, but a characteristic feature of highly prized wines. Dried grapes were used to make sweet wines, which were also highly prized, therefore justifying the construction of dedicated facilities. The addition of boiled juices, salt, resins, mixtures of herbs, spices, fruit juices, flowers, or honey to the wines would have increased their taste pleasantness while improving their preservability and medicinal properties. Indeed, today’s preference for flavored wines with a soft mouthfeel seems to have been representative of the ancient elite consumers. Overall, the technical interpretation of winemaking described in this review will provide solid historical support for the current rebirth of ancient production methods, particularly those using pottery vessels info:eu-repo/semantics/publishedVersion

Depression is a common, often recurrent disorder that causes substantial disease burden worldwide, and this is especially true for women following the pubertal transition. According to the Social Signal Transduction Theory of Depression, stressors involving social stress and rejection, which frequently precipitate major depressive episodes, induce depressive symptoms in vulnerable individuals in part by altering the activity and connectivity of stress-related neural pathways, and by upregulating components of the immune system involved in inflammation. To test this theory, we recruited adolescent females at high and low risk for depression and assessed their psychological, neural, inflammatory, and genomic responses to a brief (10 ​minute) social stress task, in addition to trait psychological and microbial factors affecting these responses. We then followed these adolescents longitudinally to investigate how their multi-level stress responses at baseline were related to their biological aging at baseline, and psychosocial and clinical functioning over one year. In this protocol paper, we describe the theoretical motivations for conducting this study as well as the sample, study design, procedures, and measures. Ultimately, our aim is to elucidate how social adversity influences the brain and immune system to cause depression, one of the most common and costly of all disorders.

Objective To verify whether aging can modify the clinical and biochemical characteristics of women with polycystic ovary syndrome (PCOS). Material and methods This observational cross-sectional study was conducted at the reproductive endocrinology clinics of Julio Muller University Hospital and Tropical Institute of Reproductive Medicine in Cuiabá, MT, Brazil, between 2003 and 2017. Both, 796 PCOS and 444 non-PCOS normal cycling women underwent the same examination. PCOS was diagnosed using the Rotterdam criteria as recommended for adolescent and adult subjects. Anthropometric, metabolic, and endocrinological modifications with aging were initially examined in the two groups: control and PCOS. Further analyses were performed after a 5-year age stratification of data throughout the reproductive period. All participants signed a consent form approved by the local ethical committee. Results Biomarkers of adiposity were more remarkable in African descendant PCOS women. Body weight, waist/hip ratio, fat mass, and BMI were higher in PCOS women and tended to increase at all 5 age-strata, between ≤19 and 35 years of age. Serum androgen levels decreased with aging, markedly in PCOS subjects (P P P = 0.041). Conclusion The present study has shown that the advancing age influences many features of PCOS women. Biochemical hyperandrogenism, the core criterion recommended in the current systems to define the syndrome, showed statistically significant tendencies to decrease with aging progression but did not normalize. The use of age-adjusted features for the diagnosis of PCOS are recommended.

The global population of individuals over the age of 65 is growing at an unprecedented rate and is expected to reach 1.6 billion by 2050. Most older individuals are affected by multiple chronic diseases, leading to complex drug treatments and increased risk of physical and cognitive disability. Improving or preserving the health and quality of life of these individuals is challenging due to a lack of well‐established clinical guidelines. Physicians are often forced to engage in cycles of “trial and error” that are centered on palliative treatment of symptoms rather than the root cause, often resulting in dubious outcomes. Recently, geroscience challenged this view, proposing that the underlying biological mechanisms of aging are central to the global increase in susceptibility to disease and disability that occurs with aging. In fact, strong correlations have recently been revealed between health dimensions and phenotypes that are typical of aging, especially with autophagy, mitochondrial function, cellular senescence, and DNA methylation. Current research focuses on measuring the pace of aging to identify individuals who are “aging faster” to test and develop interventions that could prevent or delay the progression of multimorbidity and disability with aging. Understanding how the underlying biological mechanisms of aging connect to and impact longitudinal changes in health trajectories offers a unique opportunity to identify resilience mechanisms, their dynamic changes, and their impact on stress responses. Harnessing how to evoke and control resilience mechanisms in individuals with successful aging could lead to writing a new chapter in human medicine., Finding a reference metric for the rate of biological aging is key to understanding the molecular nature of the aging process. Defining and validating this metric in humans opens the door to a new kind of medicine that will overcome the limitation of current disease definitions. We will then be able to approach health in a global perspective and bring life course preventative measures to the center of attention.

Previous research has linked exposure to adverse social conditions with DNA damage and accelerated telomere shortening, raising the possibility that chronic stress may impact biological aging pathways, ultimately increasing risk for age-related diseases. Less clear, however, is whether these stress-related effects extend to additional hallmarks of biological aging, including cellular senescence, a stable state of cell cycle arrest. The present study aimed to investigate associations between psychosocial stress and two markers of cellular aging-leukocyte telomere length (LTL) and cellular senescence signal p16INK4a. Seventy-three adults (Mage = 43.0, SD = 7.2; 55% female) with children between 8-13 years of age completed interview-based and questionnaire measures of their exposures to and experiences of stress, as well as daily reports of stress appraisals over an 8-week diary period. Blood samples were used to assess markers of cellular aging: LTL and gene expression of senescent cell signal p16INK4a (CDKN2A). Random effects models covarying for age, sex, ethnicity/race, and BMI revealed that participants with greater chronic stress exposure over the previous 6 months (b = 0.011, p = .04), perceived stress (b = 0.020, p

In an epidemic, it is important to have methods for reliable and rapid assessment of risk groups for severe forms of the disease for their priority vaccination and for the application of preventive lockdown measures. The aim of this study was to investigate risk factors for severe forms of COVID-19 in adults using indicators of biological and subjective aging. Longitudinal studies evaluated the severity of the disease and the number of cases. Respondents (447) were divided into “working group” and “risk group” (retirees with chronic diseases). During the lockdown period (in mid-2020), accelerated aging was observed in the group of workers (by 3.9–8 years for men and an increase at the tendency level for women). However, the respondents began to feel subjectively younger (by 3.3–7.2 years). In the risk group, there were no deviations from the expected biopsychological aging. The number of cases at the end of 2020 was 31% in workers and 0% in the risk group. Reasonably, the risk group followed the quarantine rules more strictly by 1.5 times. In working men, indicators of relative biological and relative subjective aging (measured in both 2019 and mid-2020) significantly influenced the incidence at the end of 2020. In women, only the indicators obtained in mid-2020 had a significant impact. The relative biological aging of an individual tested in the middle of 2020 had a direct impact on the risk of infection (p &lt, 0.05) and on the probability of death (p &lt, 0.0001). On the contrary, an increase in the relative subjective (psychological) aging index reduced the risk of infection (at the tendency level, p = 0.06) and the risk of death (p &lt, 0.0001). Both the risk of infection and the risk of death increased with calendar age at the tendency level. Conclusions: Indicators of individual relative biological and subjective aging affect the probability of getting COVID-19 and its severity. The combination of high indicators of biological aging and underestimated indicators of subjective aging is associated with increased chances of developing severe forms of the disease.

Several studies—albeit with still inconclusive and limited findings—began to focus on the effect of drinking alcohol on telomere length (TL). Here, we present results from a systematic review of these epidemiological studies to investigate the potential association between alcohol consumption, alcohol-related disorders, and TL. The analysis of fourteen studies—selected from PubMed, Medline, and Web of Science databases—showed that people with alcohol-related disorders exhibited shorter TL, but also that alcohol consumption per se did not appear to affect TL in the absence of alcohol abuse or dependence. Our work also revealed a lack of studies in the periconceptional period, raising the need for evaluating this potential relationship during pregnancy. To fill this gap, we conducted a pilot study using data and samples form the Mamma & Bambino cohort. We compared five non-smoking but drinking women with ten non-smoking and non-drinking women, matched for maternal age, gestational age at recruitment, pregestational body mass index, and fetal sex. Interestingly, we detected a significant difference when analyzing relative TL of leukocyte DNA of cord blood samples from newborns. In particular, newborns from drinking women exhibited shorter relative TL than those born from non-drinking women (p = 0.024). Although these findings appeared promising, further research should be encouraged to test any dose–response relationship, to adjust for the effect of other exposures, and to understand the molecular mechanisms involved.

Prunus spinosa L. fruit (PSF) ethanol extract, showing a peculiar content of biologically active molecules (polyphenols), was investigated for its wound healing capacity, a typical feature that declines during aging and is negatively affected by the persistence of inflammation and oxidative stress. To this aim, first, PSF anti-inflammatory properties were tested on young and senescent LPS-treated human umbilical vein endothelial cells (HUVECs). As a result, PSF treatment increased miR-146a and decreased IRAK-1 and IL-6 expression levels. In addition, the PSF antioxidant effect was validated in vitro with DPPH assay and confirmed by in vivo treatments in C. elegans. Our findings showed beneficial effects on worms’ lifespan and healthspan with positive outcomes on longevity markers (i.e., miR-124 upregulation and miR-39 downregulation) as well. The PSF effect on wound healing was tested using the same cells and experimental conditions employed to investigate PSF antioxidant and anti-inflammaging ability. PSF treatment resulted in a significant improvement of wound healing closure (ca. 70%), through cell migration, both in young and older cells, associated to a downregulation of inflammation markers. In conclusion, PSF extract antioxidant and anti-inflammaging abilities result in improved wound healing capacity, thus suggesting that PSF might be helpful to improve the quality of life for its beneficial health effects.

// Cavin K. Ward-Caviness 1 , Jamaji C. Nwanaji-Enwerem 2 , Kathrin Wolf 1 , Simone Wahl 1,3 , Elena Colicino 4 , Letizia Trevisi 5 , Itai Kloog 6 , Allan C. Just 7 , Pantel Vokonas 8 , Josef Cyrys 1 , Christian Gieger 1,3 , Joel Schwartz 2 , Andrea A. Baccarelli 4 , Alexandra Schneider 1 and Annette Peters 1 1 Institute of Epidemiology II, Helmholtz Zentrum Munchen, Neuherberg, Bavaria, Germany 2 Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA 3 Research Unit Molecular Epidemiology, Helmholtz Zentrum Munchen, Neuherberg, Bavaria, Germany 4 Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA 5 Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA 6 Department of Geography and Environmental Development, Ben-Gurion University of the Negev, Beer Sheva, Israel 7 Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA 8 VA Normative Aging Study, Veterans Affairs Boston Healthcare System and the Department of Medicine, Boston University School of Medicine, Boston, MA, USA Correspondence to: Annette Peters, email: // Keywords : epigenetic aging, telomere length, biological aging, air pollution, black carbon, Gerotarget Received : June 10, 2016 Accepted : October 13, 2016 Published : October 25, 2016 Abstract Long-term exposure to air pollution is associated with age-related diseases. We explored the association between accelerated biological aging and air pollution, a potential mechanism linking air pollution and health. We estimated long-term exposure to PM 10 , PM 2.5 , PM 2.5 absorbance/black carbon (BC), and NO x via land-use regression models in individuals from the KORA F4 cohort. Accelerated biological aging was assessed using telomere length (TeloAA) and three epigenetic measures: DNA methylation age acceleration (DNAmAA), extrinsic epigenetic age acceleration (correlated with immune cell counts, EEAA), and intrinsic epigenetic age acceleration (independent of immune cell counts, IEAA). We also investigated sex-specific associations between air pollution and biological aging, given the published association between sex and aging measures. In KORA an interquartile range (0.97 µg/m 3 ) increase in PM 2.5 was associated with a 0.33 y increase in EEAA (CI = 0.01, 0.64; P = 0.04). BC and NO x (indicators or traffic exposure) were associated with DNAmAA and IEAA in women, while TeloAA was inversely associated with BC in men. We replicated this inverse BC-TeloAA association in the Normative Aging Study, a male cohort based in the USA. A multiple phenotype analysis in KORA F4 combining all aging measures showed that BC and PM 10 were broadly associated with biological aging in men. Thus, we conclude that long-term exposure to air pollution is associated with biological aging measures, potentially in a sex-specific manner. However, many of the associations were relatively weak and further replication of overall and sex-specific associations is warranted.

Telomere length, a marker of biological aging, has been associated with cardiovascular disease (CVD). Increased arterial stiffness, an indicator of arterial aging, predicts adverse CVD outcomes. However, the relationship between telomere length and arterial stiffness is less well studied. Here we examined the cross-sectional association between leukocyte telomere length (LTL) and arterial stiffness in 2,165 American Indians in the Strong Heart Family Study (SHFS). LTL was measured by qPCR. Arterial stiffness was assessed by stiffness index β. The association between LTL and arterial stiffness was assessed by generalized estimating equation model, adjusting for sociodemographics (age, sex, education level), study site, metabolic factors (fasting glucose, lipids, systolic blood pressure, and kidney function), lifestyle (BMI, smoking, drinking, and physical activity), and prevalent CVD. Results showed that longer LTL was significantly associated with a decreased arterial stiffness (β=-0.070, P=0.007). This association did not attenuate after further adjustment for hsCRP (β=-0.071, P=0.005) or excluding participants with overt CVD (β=-0.068, P=0.012), diabetes (β=-0.070, P=0.005), or chronic kidney disease (β=-0.090, P=0.001). In summary, shorter LTL was significantly associated with an increased arterial stiffness, independent of known risk factors. This finding may shed light on the potential role of biological aging in arterial aging in American Indians.

Multimorbidity and depression are complex multifactorial conditions with major implications for older individuals, their families, and healthcare providers. In this scoping review, we aimed to 1) review findings from longitudinal epidemiological studies investigating the association between multimorbidity and depression; 2) identify potential mechanisms linking multimorbidity and depression; 3) discuss challenges to advance the research field. Overall, evidence emerging from longitudinal studies supports a bidirectional association between the two conditions, although studies are methodologically heterogeneous in terms of design, inclusion criteria, measurement of multimorbidity and depression, and length of follow-up. A variety of biological, psychosocial, and care-related drivers may regulate the transition from multimorbidity to depression, and the other way around, although these mechanisms are yet to be explicitly verified. Further research is required to unravel the intricate interplay between multimorbidity, depression, their common drivers, and precipitating factors underlying the relationship between the two conditions. Understanding these processes will inform strategies aimed at promoting mental and physical health during aging.

Man ages at a constant chronological rate while their biological aging rate is extremely variable. Interventions to improve, or to slow the rate of biological aging are the subject of several research. The broad spectrum of molecules and its intricate role from the biological point of view and its relation with environmental factors are being investigated. Recently, researchers have been putting its efforts to understand the epigenetic mechanisms and how it can interfere with alterations in gene expression that leads to predisposition and, or pathological outcome. Some of these investigations have shed light about how one can determine the biological age from a simple blood sample, just by detecting the epigenetic alterations on only three CpGs sites with a reasonable certainty. Also, the enzymes inhibitors that can interfere with methylation and demethylation were effective to reverse the epigenetic mechanisms. Other studies have shown how the environmental changes since from early life can affect these alterations on the epigenome. Taking all together, some biomolecular markers are already available to determine the genetic background of an individual and this information can be used to guide the lifestyle in order to prevent some future diseases development and/or improve the quality of later life. El hombre envejece a una tasa cronológica constante, mientras que su tasa de envejecimiento biológico es extremadamente variable. Las intervenciones para mejorar o disminuir la tasa de envejecimiento biológico son objeto de várias investigaciones. Se está investigando el amplio espectro de moléculas y su intrincado papel desde el punto de vista biológico y su relación con los factores ambientales. Recientemente, los investigadores han estado poniendo sus esfuerzos para comprender los mecanismos epigenéticos y cómo puede interferir con las alteraciones en la expresión génica que conducen a la predisposición y/o al resultado patológico. Algunas de estas investigaciones han arrojado luz sobre cómo se puede determinar la edad biológica a partir de una muestra de sangre simple, simplemente detectando las alteraciones epigenéticas en solo tres sitios CpG con una certeza razonable. Además, los inhibidores de enzimas que pueden interferir con la metilación y la desmetilación fueron efectivos para revertir los mecanismos epigenéticos. Otros estudios han demostrado cómo los cambios ambientales desde la vida temprana pueden afectar estas alteraciones en el epigenoma. En conjunto, algunos marcadores biomoleculares ya están disponibles para determinar el origen genético de un individuo y esta información se puede utilizar para guiar el estilo de vida a fin de prevenir el desarrollo de enfermedades futuras y / o mejorar la calidad de la vida posterior. O homem envelhece a uma taxa cronológica constante, enquanto a taxa de envelhecimento biológico é extremamente variável. Intervenções para melhorar ou reduzir a taxa de envelhecimento biológico tem sido objeto de várias pesquisas. O amplo espectro de moléculas e suas complexas funções biológicas, bem como sua relação com os fatores ambientais tem sido investigado e os pesquisadores tem se dedicado a compreensão dos mecanismos epigenéticos e como podem interferir nas alterações de expressão gênica que leva a predisposição ou a um desfecho patológico. Algumas dessas investigações identificou como podemos determinar a idade biológica a partir de uma simples amostra de sangue, por meio da detecção de alterações epigenéticas em somente três ilhas CpGs com ampla margem de segurança. Igualmente, os inibidores das enzimas que atuam nos processos de metilação e desmetilação foram eficazes na reversão dos mecanismos epigenéticos. Outros estudos mostraram como as alterações ambientais, desde o início da vida, podem afetar o epigenome. Resumindo, alguns marcadores moleculares para determinar o perfil genético de um indivíduo já estão disponíveis e esta informação poderá ser usada para orientar o estilo de vida visando a prevenção e/ou desenvolvimento de futuras doenças melhorando a qualidade de vida do ser humano na idade mais avançada.

BACKGROUND:Biological aging pathways accelerated by cancer treatments may be a mechanism for cognitive impairment in cancer survivors. The goal of the current study was to examine whether indicators of biological aging, namely elevated levels of DNA damage, reduced telomerase enzymatic activity, and shorter peripheral blood mononuclear cell (PBMC) telomere length (TL) would be related to cognitive function in a cohort of survivors of breast cancer. METHODS:The authors evaluated a cross-sectional sample of 94 women aged 36 to 69 years who were treated for early-stage breast cancer 3 to 6 years previously. Leukocyte DNA damage, PBMC telomerase enzymatic activity, PBMC TL, and the inflammatory marker soluble tumor necrosis factor receptor II (sTNF-RII) were determined from blood samples. Cognitive function was assessed using a neuropsychological test battery and self-report. Linear regression models examined the relationship between biological aging predictors and cognitive outcomes. RESULTS:Both higher DNA damage and lower telomerase were found to be statistically significantly related to lower executive function scores adjusting for age, body mass index, race, years from treatment, and intelligence score (standardized coefficients [B], -0.23 and 0.30; all P values

Higher vitamin D status, lower adiposity, and longer telomere length are each reportedly associated with lower risk of several chronic diseases and all-cause mortality. However, direct relationships between vitamin D status (measured by circulating 25-hydroxyvitamin D (25(OH)D) concentration), adiposity, and telomere length are not well established. We conducted a cross-sectional analysis of associations of 25(OH)D and body mass index (BMI; weight (kg)/height (m)2) with mean relative leukocyte telomere length (LTL) using data gathered on 5,096 participants from Northern Finland Birth Cohort 1966 at age 31 years (1997). 25(OH)D was not associated with LTL in either basic or confounder/mediator-adjusted models. BMI was inversely associated with LTL after adjustment for potential confounding by age, sex, socioeconomic position, physical activity, diet, smoking, alcohol intake, and use of oral contraceptives (per 1-unit increase in BMI, mean difference in LTL = −0.4%, 95% confidence interval: −0.6, −0.2). The BMI-LTL association was also independent of 25(OH)D and was attenuated slightly, but remained, after adjustment for C-reactive protein, a marker of low-grade inflammation (mean difference in LTL = −0.3%, 95% confidence interval −0.6, −0.1). These findings suggest that vitamin D status is unlikely to be an important determinant of LTL, at least by young adulthood. Inflammation may partly mediate associations of adiposity with LTL. This work was supported financially by the following institutions: the Academy of Finland (grants 104781, 120315, 129269, 1114194, 24300796, and 12926); University Hospital Oulu and Biocenter Oulu, University of Oulu (grant 75617); the European Commission (grant QLG1-CT-2000- 01643); the National Heart, Lung, and Blood Institute, US National Institutes of Health (grant 5R01HL087679-02); the National Institute of Mental Health, US National Institutes of Health (grant 5R01MH63706:02); the Medical Research Council (grants G0500539, G0600705, G0601653, and K014536); the Wellcome Trust (grant GR069224); and Diabetes UK (grant 08/0003775). J.L.B. was supported by a Wellcome Trust Fellowship grant (WT088431MA). D.M.W., S.S., and M.-R.J. were supported by the European Union’s Horizon 2020 research and innovation program under grant agreement DynaHEALTH (633595).

Intervention studies in animals suggest molecular changes underlying age-related disease and disability can be slowed or reversed. To speed translation of these so-called “geroprotective” therapies to prevent age-related disease and disability in humans, biomarkers are needed that can track changes in the rate of human aging over the course of intervention trials. Algorithm methods that measure biological processes of aging from combinations of DNA methylation marks or clinical biomarkers show promise. To identify next steps for establishing utility of these algorithm-based measures of biological aging for geroprotector trials, we considered the history a candidate biomarker of aging that has received substantial research attention, telomere length. Although telomere length possesses compelling biology to recommend it as a biomarker of aging, mixed research findings have impeded clinical and epidemiologic translation. Strengths of telomeres that should be established for algorithm biomarkers of aging are correlation with chronological age across the lifespan, prediction of disease, disability, and early death, and responsiveness to risk and protective exposures. Key challenges in telomere research that algorithm biomarkers of aging must address are measurement precision and reliability, establishing links between longitudinal rates of change across repeated measurements and aging outcomes, and clarity over whether the biomarker is a causal mechanism of aging. These strengths and challenges suggest a research agenda to advance translation of algorithm-based aging biomarkers: establish validity in young-adult and midlife individuals; test responsiveness to exposures that shorten or extend healthy lifespan; and conduct repeated-measures longitudinal studies to test differential rates of change.

This review is an attempt to compile current knowledge on concepts and transformations that occur naturally in the human body and that characterize what is defined today as biological aging with quality of life and longevity. Many authors define natural aging as a continuous and uninterrupted process, which occurs in the human body causing structural and functional changes, classified as: cumulative, progressive, intrinsic and deleterious (CUPID). Usually these changes begin early in life and culminate in physical death. Genetic, chemical and biochemical changes lead to progressive degeneration of cells, tissues and organs, body systems and the organism as a whole, leading to loss of structures and functions due to aging. All these changes were discussed in some detail in the review here presented. We concluded that aging is not genetically determined, resulting in the accumulation of cellular and tissue damage, particularly in chromatin and DNA within cells, in addition to structural and bioactive proteins that command the general metabolism. Environmental factors such as feeding (nutrition) and lifestyle were also discussed. Resumo Esta revisão é uma tentativa de compilação do conhecimento atual sobre conceitos e transformações que ocorrem naturalmente no corpo humano e que caracterizam o que se define, hoje, como envelhecimento biológico saudável, com qualidade de vida e longevidade. Vários autores definem envelhecimento natural como um processo contínuo e ininterrupto, que ocorre no corpo humano provocando mudanças estruturais e funcionais, qualificadas como cumulativas, progressivas, intrínsecas e deletérias (CUPID). Normalmente, essas alterações começam muito cedo na vida e culminam na morte física. Mudanças de natureza genética, química e bioquímica conduzem a degradações progressivas das células, dos tecidos e órgãos, dos sistemas e do organismo como um todo, promovendo, com a idade, perdas de estruturas e funções. Todas estas alterações foram discutidas, em algum detalhe, ao longo da revisão apresentada. Concluiu-se que o envelhecimento não é geneticamente programado, resultando no acúmulo de danos celulares e teciduais, particularmente na cromatina e no DNA, no interior das células, e nas proteínas estruturais e bioativas, que comandam o metabolismo geral. Fatores ambientais, como alimentação (nutrição) e estilo de vida, também foram discutidos.

Comment on: “Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies” by Steve Horvath, et al. published in Aging Volume 10, Issue 7, pp 1758—75. http://www.aging-us.com/article/101508/text

Fino is the most popular sherry wine produced in southern Spain. Fino is matured by biological aging under a yeast biofilm constituted of Saccharomyces cerevisiae yeasts. Although different S. cerevisiae strains can be identified in such biofilms, their diversity and contribution to wine character have been poorly studied. In this work, we analyse the flor yeast population in five different wineries from the Montilla-Moriles D.O. (Denominación de Origen) in southern Spain. Yeasts present in wines of different ages were identified using two different culture-dependent molecular techniques. From 2000 individual yeast isolates, five different strains were identified with one of them dominating in four out of the five wineries analysed, and representing 76% of all the yeast isolates collected. Surprisingly, this strain is similar to the predominant strain isolated twenty years ago in Jerez D.O. wines, suggesting that this yeast is particularly able to adapt to such a stressful environment. Fino wine produced with pure cultures of three of the isolated strains resulted in different levels of acetaldehyde. Because acetaldehyde levels are a distinctive characteristic of fino wines and an indicator of fino aging, the use of molecular techniques for yeast identification and management of yeast populations may be of interest for fino wine producers looking to control one of the main features of this wine., This work was supported by Junta de Andalucía Grant AGR 05241. MMM was supported by a fellowship from the Junta de Andalucía AGR 05241.