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The past decade marked the beginning of the use of resting‐state functional connectivity (RSFC) imaging in bilingualism studies. This paper intends to review the latest evidence of changes in RSFC in language and cognitive control networks in bilinguals during adulthood, aging, and early Alzheimer's disease, which can add to our understanding of brain functional reshaping in the context of second language (L2) acquisition. Because of high variability in bilingual experience, recent studies mostly focus on the role of the main aspects of bilingual experience (age of acquisition (AoA), language proficiency, and language usage) on intrinsic functional connectivity (FC). Existing evidence accounts for stronger FC in simultaneous rather than sequential bilinguals in language and control networks, and the modulation of the AoA impact by language proficiency and usage. Studies on older bilingual adults show stronger FC in language and frontoparietal networks and preserved FC in posterior brain regions, which can protect the brain against cognitive decline and neurodegenerative processes. Altered RSFC in language and control networks subsequent to L2 training programs also is associated with improved global cognition in older adults. This review ends with a brief discussion of potential confounding factors in bilingualism research and conclusions and suggestions for future research. [ABSTRACT FROM AUTHOR]

This paper presents a new two-sex learning- and skills-based theory for the evolution of human menopause. The theory proposes that the role of knowledge, skill acquisition, and transfers in determining economic productivity and resource distribution is the distinctive feature of the traditional human ecology that is responsible for the evolution of menopause. The theory also proposes that male reproductive cessation and post-reproductive investment in descendants is a fundamental characteristic of humans living in traditional foraging and simple horticultural economies. We present evidence relevant to the theory. The data show that whereas reproductive decline is linked to increasing risks of mortality in chimpanzees, human reproductive senescence precedes somatic senescence. Moreover under traditional conditions, most human males undergo reproductive cessation at the same time as their wives. We then present evidence that after ceasing to reproduce, both men and women provide net economic transfers to children and grandchildren. Given this pattern of economic productivity, delays in menopause would produce net economic deficits within families. [ABSTRACT FROM AUTHOR]

This commentary discusses the intersection of human ovarian and somatic aging. It argues for re-contextualizing estrogen's role in and impact on ovarian aging and, more broadly, on women's health, considering in particular the importance of timing, dose, and the broader endocrine milieu. Distinguishing between current clinical needs and optimizing women's future options, the paper outlines an approach to broadening the research agenda to better understand the role of ovarian aging in supporting the metabolic demands of longevity. Three overarching issues important to consider explicitly as we pursue research on the health correlates of reproductive aging are discussed, including implications of a lifespan approach, population diversity, and selection bias. [ABSTRACT FROM AUTHOR]

The Intergenerational Report (IGR) released by the Department of the Treasury of the Commonwealth of Australia in 2002 highlighted pressures that in the future would threaten the sustainability of the Australian government's budget balance. These pressures result from the growing needs of an aging population and labor shortages that will limit economic growth and taxation revenue. The IGR has become a driving force in planning government policy. The Treasurer has recently said that “the whole economic agenda of the government at the moment is drawn from the IGR.” In response, the Prime Minster and Treasurer have promoted deferred or gradual retirement as part of the solution. However, about 50% of men and 20% of women retire early as a result of ill health, indicating that poor health is potentially a limiter of economic growth. This paper reports lower labor force participation among persons with poorer health and that these persons move out of the labor force at a faster rate as they age. A range of measures suggests some decline in health in the pre-retirement age group (those aged from 40 to 64 years). This indicates that better health may be a facilitator of greater labor force participation in the baby boomer cohort. However, there is evidence that improving economic conditions in Australia leading to low unemployment has created an environment more favorable to the employment of older workers with health problems as there has been a rise in labor force participation in these groups, and measures to prevent chronic disease may further increase the employment prospects. [ABSTRACT FROM AUTHOR]

The potential of a transdisciplinary research method—Quali-Quantitative Analysis (QQA)—for delivering better evidence for healthy aging is explored. Illustrative reviews from the literature on healthy aging are summarized, as are papers on methodology by Charles Ragin and colleagues. The evidence needs for healthy aging are explored, particularly in relation to the ability of randomized controlled trials (RCTs) to deliver rich, diversity-oriented evidence. The techniques of QQA, which involves treating cases as configurations, are described. The QQA method has potential value for healthy aging research in that: ( a) it could provide evidence in combinatorial forms useful to holistic practice; ( b) it could enrich the evidence for practice by providing more rigorous information from small- N groups, within RCTs and where RCTs cannot be used; and ( c) it could add to the ability of RCTs to generate theoretical advances. [ABSTRACT FROM AUTHOR]

Implementing community services can be a very complex process where people end up “not seeing the wood for the trees” and then accepting a compromise nobody wants. Neither agency theory nor stewardship theory is particularly robust when explaining the reality that funders and managers of community health service for older people face in managing contracts. There are particular difficulties with goal divergence between policy directives and implementation practices, which result from goals not being well understood and performance requirements being ambiguously defined and infrequently monitored. This leads to accountability issues for public managers, and raises efficiency and effectiveness issues. This paper provides an interim report on a project developing a management-control system to provide a process for health planners and funders to use when developing and contracting services. A major focus is inviting stakeholders into a process of communication that ensures that they have shared understandings of where they want to get to, and what has to be done to get there. [ABSTRACT FROM AUTHOR]

Increasing longevity and the growing proportion of the aged in the population in most countries have served to focus on the question of how governments and older people can finance living, health, and care options in retirement. Prudent management of income and assets is an increasingly complex and important aspect of aging as assets and expectations of self-financing increase. Although many informal caregivers act as asset managers and/or substitute decision-makers for older people, little attention has been paid to this increasingly important aspect of care. This paper summaries key findings of a broad research program exploring family involvement in the management of older people's assets and the practices that constitute good practice as well as financial mismanagement and abuse. It identifies multi-level and multi-strategy responses needed to address the issues raised by the research and outlines an innovative community demonstration project aimed at improving financial management practices in relation to older people's assets. [ABSTRACT FROM AUTHOR]

Lifestyle factors have been identified as being very important in determining health in later life. Nutrition, exercise, and social environment all interact to promote, or to limit, opportunities for an active and healthy post-working life. Not only are rates of chronic illness and disability reduced through the promotion of healthy lifestyles, but also quality of life is maintained through the compression of morbidity. Governments in Australia, as in the European Union and North America, have highlighted the importance of behavioral change in health promotion strategies with the aim of having an impact on the health-related lifestyles of their populations. This paper examines the example of a group of older Australians, the “grey nomads,” who may present opportunities for examining health-related lifestyle changes. The term grey nomad refers to a portion of the older population in Australia who choose to use their later years and retirement as opportunities for travel and leisure, mainly within the confines of the Australian continent. As such, they are similar to groups in North America, such as the “snow birds,” who travel to the southern United States to escape the colder winters of more northerly latitudes. Similar seasonal migrations occur from Northern to Southern Europe. What all share in common is an active culture/lifestyle of attempting to “age successfully.” Grey nomads also participate in the creation of what can be termed postmodern communities, where they and other regular travelers may develop a sense of community feeling with others who are also regularly returning to the same spot year after year. Social support is highly predictive of health outcomes and such mobile communities may prove a positive factor in promoting good health. In this paper we examine whether the “grey nomads” represent a good model for improving health-related lifestyles in later life. [ABSTRACT FROM AUTHOR]

Interventions that improve health are often associated with longevity. Reduced growth hormone signaling has been shown to increase life span in mice by over 50%. Similarly, reductions in dietary intake of methionine, in rats and mice, result in life-span extension. Many factors affect metabolic health, mitochondrial function, and resistance to stressors, each of which influence aging and life span. This paper presents a comparison of these two interventions, as well as the results of a study combining these interventions, to understand potential mechanisms underlying their effectiveness in enhancing healthy aging. [ABSTRACT FROM AUTHOR]

This paper reviews quantitative and qualitative studies conducted to identify changes in the characteristics of hematopoietic stem/progenitor cells (HSCs/HPCs) with or without radiation exposure. The numerical recovery of HSCs/HPCs after radiation exposure is lower than for other types of cells, an effect that may depend on hierarchical ordering of generation age during blood cell differentiation, from primitive HSCs to various differentiated HPCs. Studies are in progress to evaluate gene expression in bone marrow cells and cells in the lineage-negative, c-Kit+, stem cell antigen+ (LKS) fraction from 21-month-old mice, with or without radiation exposure. Preliminary data suggest that cell cycle-related genes, that is, cyclin D1 ( Ccnd1), phosphatidylinositol 3 kinase regulatory subunit polypeptide 1 ( PiK3r1), and Fyn, are upregulated solely in the LKS fraction from 21-month-old mice irradiated at 6 weeks of age, compared with the LKS fraction from age-matched nonirradiated control mice. Additional studies may provide evidence that the aging phenotype is exaggerated following exposure to ionizing radiation, specifically in the LKS fraction. [ABSTRACT FROM AUTHOR]

With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline. [ABSTRACT FROM AUTHOR]

A growing body of research suggests that meditation practices are associated with substantial psychological as well as physiological benefits. In searching for the biological mechanisms underlying the beneficial impact of meditation, studies have revealed practice-induced alterations of neurotransmitters, brain activity, and cognitive abilities, just to name a few. These findings not only imply a close link between meditation and brain structure, but also suggest possible modulating effects of meditation on age-related brain atrophy. Given that normal aging is associated with significant loss of brain tissue, meditation-induced growth and/or preservation might manifest as a seemingly reduced brain age in meditators (i.e., cerebral measures characteristic of younger brains). Surprisingly, there are only three published studies that have addressed the question of whether meditation diminishes age-related brain degeneration. This paper reviews these three studies with respect to the brain attributes studied, the analytical strategies applied, and the findings revealed. The review concludes with an elaborate discussion on the significance of existing studies, implications and directions for future studies, as well as the overall relevance of this field of research. [ABSTRACT FROM AUTHOR]

The intervention strategies in various types of skin wounds include several treatment programs that depend on the identified disease. Several factors such as aging, defective nutrition, traumatism, atherosclerosis, and diabetes may contribute to the formation of a wound that has no tendency to heal due to a defective and complicated repair process. The numerous advances in the understanding of the wound-healing process in both acute and chronic lesions have been recently described. The purpose of this paper is to describe relatively new approaches as viable alternatives to current wound-healing therapies. The future challenges for both the best targeting and optimization of these potential treatments are also described. [ABSTRACT FROM AUTHOR]

This paper reviews age differences in emotion processing and how they may relate to age-related changes in the brain. Compared with younger adults, older adults react less to negative situations, ignore irrelevant negative stimuli better, and remember relatively more positive than negative information. Older adults' ability to insulate their thoughts and emotional reactions from negative situations is likely due to a number of factors, such as being less influenced by interoceptive cues, selecting different emotion regulation strategies, having less age-related decline in prefrontal regions associated with emotional control than in other prefrontal regions, and engaging in emotion regulation strategies as a default mode in their everyday lives. Healthy older adults' avoidance of processing negative stimuli may contribute to their well-maintained emotional well-being. However, when cardiovascular disease leads to additional prefrontal white matter damage, older adults have fewer cognitive control mechanisms available to regulate their emotions, making them more vulnerable to depression. In general, although age-related changes in the brain help shape emotional experience, shifts in preferred strategies and goal priorities are also important influences. [ABSTRACT FROM AUTHOR]

Translational medicine must increasingly turn its attention to the aging population and the musculoskeletal deterioration that it entails. The latter involves the integrated function of both muscle and bone. Musculoskeletal science has an established interest in such problems in relationship to osteoporosis of bone. The introductory concepts in this paper consider the extent to which loss of muscle mass and function, or sarcopenia, will be the next major translational target. Its epidemiology shows parallels with that of osteoporosis, and the two tissues have a close functional relationship. Its etiology likely involves a loss of motor units combined with cellular signaling and endocrine changes. Finally, the possibility of modification of these physiological changes in the context of management of the sarcopenic condition is considered. [ABSTRACT FROM AUTHOR]

In this paper, we review the current literature to highlight relations between age-associated declines in dopaminergic and serotonergic neuromodulation and adult age differences in adaptive goal-directed behavior. Specifically, we focus on evidence suggesting that deficits in neuromodulation contribute to older adults' behavioral disadvantages in learning and decision making. These deficits are particularly pronounced when reward information is uncertain or the task context requires flexible adaptations to changing stimulus-reward contingencies. Moreover, emerging evidence points to age-related differences in the sensitivity to rewarding and aversive outcomes during learning and decision making if the acquisition of behavior critically depends on outcome processing. These age-related asymmetries in outcome valuation may be explained by age differences in the interplay of dopaminergic and serotonergic neuromodulation. This hypothesis is based on recent neurocomputational and psychopharmacological approaches, which suggest that dopamine and serotonin serve opponent roles in regulating the balance between approach behavior and inhibitory control. Studying adaptive regulation of behavior across the adult life span may shed new light on how the aging brain changes functionally in response to its diminishing resources. [ABSTRACT FROM AUTHOR]

The human brain is a complex network. An important first step toward understanding the function of such a network is to map its elements and connections, to create a comprehensive structural description of the network architecture. This paper reviews current empirical efforts toward generating a network map of the human brain, the human connectome, and explores how the connectome can provide new insights into the organization of the brain's structural connections and their role in shaping functional dynamics. Network studies of structural connectivity obtained from noninvasive neuroimaging have revealed a number of highly nonrandom network attributes, including high clustering and modularity combined with high efficiency and short path length. The combination of these attributes simultaneously promotes high specialization and high integration within a modular small-world architecture. Structural and functional networks share some of the same characteristics, although their relationship is complex and nonlinear. Future studies of the human connectome will greatly expand our knowledge of network topology and dynamics in the healthy, developing, aging, and diseased brain. [ABSTRACT FROM AUTHOR]

Previous studies in postmenopausal women have reported that estrogen treatment (ET) modulates the risk for developing Alzheimer's disease (AD). It has recently been hypothesized that there may be a 'critical period' around the time of menopause during which the prescription of ET may reduce the risk of developing AD in later life. This effect may be most significant in women under 49 years old. Furthermore, prescription of ET after this point may have a neutral or negative effect, particularly when initiated in women over 60-65 years old. In this paper, we review recent studies that use in vivo techniques to analyze the neurobiological mechanisms that might underpin estrogen's effects on the brain postmenopause. Consistent with the 'critical period' hypothesis, these studies suggest that the positive effects of estrogen are most robust in young women and in older women who had initiated ET around the time of menopause. [ABSTRACT FROM AUTHOR]

Woman's sexuality encompasses sexual identity, sexual function, and sexual relationships. It is modulated throughout life by life and reproduction-related events, health, relationships, and sociocultural variables. The aging process and menopause are two potent contributors to female sexual dysfunction. The earlier the menopause, the more severe and complex the impact on sexuality is. The younger the woman, the less she realizes the different key goals of her life cycle (falling in love, having a satisfying sexual life, forming a stable couple, getting married, having a family) and the more pervasive the consequences on her sexual identity, sexual function, and sexual relationship can be. Premature menopause is an amplified paradigm of the complex impact menopause can have on women's and couple's sexuality. This paper will focus on biologically based sexual issues, namely desire, arousal, orgasm, and pain disorders, as well as key questions encountered in infertility. The concepts of 'symptom inducer' and 'symptom carrier' will also be addressed. [ABSTRACT FROM AUTHOR]

The broad objective of this paper is to present an overview and synthesis of selected studies on reproduction and aging in two model tephritid fruit fly species including the Mediterranean fruit fly, Ceratitis capitata, and the Mexican fruit fly, Anastrepha ludens. We summarize the research findings from empirical studies and modeling investigations involving reproduction in the two tephritid species. At the end we identify and discuss four general principles regarding reproductive aging in tephritids including reciprocity of reproductive and aging costs, qualitative tradeoffs, plasticity of lifespan and reproduction, and life history constraints and determinacy. [ABSTRACT FROM AUTHOR]

The American philosopher John Rawls describes a fair system of social cooperation as one that is both rational and reasonable. Is it rational and reasonable for societies that (1) are vulnerable to diverse risks of morbidity ( e.g., cancer, heart disease) and mortality and (2) are constrained by limited medical resources, to prioritize aging research? In this paper I make the case for answering “yes” on both accounts. Focusing on a plausible example of an applied gerontological intervention ( i.e., an antiaging pharmaceutical), I argue that the goal of decelerating the rate of human aging would be a more effective strategy for extending the human health span than the current strategy of just tackling each specific disease of aging. Furthermore, the aspiration to retard human aging is also a reasonable aspiration, for the principle that underlies it ( i.e., the duty to prevent harm) is one that no one could reasonably reject. [ABSTRACT FROM AUTHOR]

With global trends toward population aging, many countries are adopting healthy aging policies to minimize disability and increase quality in the extended years of life. Falls in older people are a major contributor to functional decline generally associated with aging. Based on a study quantifying the relationship between healthy aging factors and risk of fall-related hip fracture in community-dwelling older people, this paper discusses evidence for the promotion of healthy aging as a population-based intervention for prevention of injuries from falls. To examine the protective effect of healthy aging on the risk of fall-related hip fractures, a case–control study was conducted with 387 participants. Persons aged 65 and over hospitalized with a fall-related hip fracture were matched with community-based controls recruited via electoral roll sampling. A questionnaire designed to assess lifestyle risk factors, identified as determinants of healthy aging, was administered during face-to-face interviews. After adjustment for health status and demographic factors, a number of lifestyle factors were seen to have a significant independent protective effect on the risk of hip fracture. These included never smoking, moderate alcohol consumption, being active, maintaining normal weight, and being proactive in preventive health care. Psychosocial factors included having supportive environments and personal resources to cope with stress. This study identified a range of modifiable lifestyle factors associated with fall-related hip fracture, suggesting that the “healthy aging” paradigm offers a comprehensive approach to falls injury prevention, and thus supports the adoption of healthy aging policies to extend years of quality life among older persons. [ABSTRACT FROM AUTHOR]

While aging is associated with physical decline and increased risk of illness, older age is not inevitably a time of ill-being. Data from the Australian Longitudinal Study on Women's Health challenge negative stereotypes of aging and illness. While an accelerating decline in average physical health was observed over the first 6 years of the study, an important and large proportion of the women experienced minimal change in their physical health during this period. Also, while chronic disease was a strong risk factor for declining health, many women aged well in spite of longstanding medical conditions. This paper presents trends in health and illness as women age and explores some of the many physical, social, and healthcare factors that mark out those women who remain “fit and well.” [ABSTRACT FROM AUTHOR]

Malaysia is steadily progressing toward an aging population demographic pattern. While aging is a natural process, its impact can be painful individually as well as for the nation. Individually there is a loss of a paying job after retirement, loss of physical and mental fitness, and also occasionally the loss of social integration due to lack of mobility. For a nation, an aging population means a growing dependency ratio, a greater need of care, and more medical facilities for this age group. This article looks at the various economic and social implications of the aging population in Malaysia in general, and in the rural and urban setting specifically. The paper focuses on a research sample of 132 (66 rural, 66 urban) elderly persons. The findings suggest that the demographic patterns of the elderly vary from the rural to the urban setting, with differing issues that need to be addressed to alleviate problems encountered related to loneliness, lack of financial stability, and emotional strain. Policy suggestion will be geared toward providing a solution to problems at hand as well as aiding the working group members to prepare and sustain a comfortable livelihood for the aged in their later years. [ABSTRACT FROM AUTHOR]

Recent developments in aging research have added new urgency to the bioethical debate concerning life and death issues, the value of life, and the reasonable limits of medicine. This paper analyzes the basic structures of the liberal and conservative components of this debate, showing that there has hitherto been inadequate analysis on both sides concerning the nature and implications of the value of life, as well as, and as distinct from the value of life extension. Classic concepts of the intrinsic or extrinsic value of life are argued to be tangential or actually irrelevant to the value of life's continuance and so to the value of life extension. An analysis of personhood is proposed which focuses explicitly upon the value of life extension to persons. This analysis shows that persons may only intelligibly be understood as processes, for whom life extension is an inalienable and fundamental value. It is further proposed that, properly understood, such an analysis may significantly narrow the liberal/conservative divide in bioethics. [ABSTRACT FROM AUTHOR]

Aminoguanidine (AG), a prototype therapeutic dicarbonyl scavenger, is the most potent drug available today to inhibit the formation of advanced glycation endproducts (AGEs) and to reverse glycation-mediated damage in normal aging. This paper examines the ability of AG to cause damage to supercoiled plasmid DNA in the presence of the transition metal, Fe+3. Damage to DNA was dependent on the concentrations of both the transition metal and AG. We could detect hydroxyl radical as well as hydrogen peroxide during the incubation of AG with Fe+3. Thus this finding further cautions against the indiscriminate use of AG in clinical prophylaxis in diabetes and questions its use as a therapeutic agent. [ABSTRACT FROM AUTHOR]

This paper characterizes the distribution of telomere length on individual chromosome arms in humans. By fluorescent in situ hybridization (FISH), followed by computer-assisted analysis of digital images, it is shown that the distribution of telomere length on individual chromosome arms is not random, but that humans have a common telomere profile. This profile exists in lymphocytes, amniocytes and fibroblasts, and seems to be conserved during life. A closer look at the overall pattern of the profile shows that the length of the telomeres in general follows the total chromosome length. In addition to the common profile, it is found that each person has specific characteristics, which are also conserved throughout life. Studying both twins and families we have obtained indications that these individual characteristics are at least partly inherited. Altogether, our results suggest that the length of individual telomeres might occasionally play a role in the heritability of life span. [ABSTRACT FROM AUTHOR]

The article presents the author's views about the Fourth Stromboli Conference on Aging and Cancer that was held on the island of Stromboli, Italy. The author says that Walter Pierpaoli, organizer of the conference has done a splendid job of assembling highly qualified clinicians and scientists from the four corners of the world. The author further said that most of the papers were excellent, adding to the scientific basis for future clinical improvements in the treatment of cancer and aging.

The article presents the author's views about the Fourth Stromboli Conference on Aging and Cancer that was held on the island of Stromboli, Italy. The author says that Walter Pierpaoli, organizer of the conference has done a splendid job of assembling highly qualified clinicians and scientists from the four corners of the world. The author further said that most of the papers were excellent, adding to the scientific basis for future clinical improvements in the treatment of cancer and aging.

According to the redusome hypothesis, the aging of an organism is determined by the shortening of chronomeres (small perichromosomal linear DNA molecules). In this paper, a presumptive role for infradian hormonal rhythms is considered. Endogenous infradian rhythms are supposed to actively interact with those hormonal shifts which are governed by an exogenous infradian gravitational lunar rhythm. As a result of this interaction, the so-called Trhythm is formed. Peaks of T-rhythms are used as the pacemaker signals to keep the life-long "clockwork" of the brain running. The "ticking" of this clock is realized by the periodically repeated shortening of chronomeres in postmitotic neuroendocrine cells, which occurs just at the maxima of T-rhythms. Shortening of telomeres in mitotic cells in vivo is a witness of the aging of the organism, but not the cause of aging. The primary cause of aging is shortening of chronomeres, the material carriers of a temporal program of development and aging. To recognize exogenous gravitational infradian rhythms, a special physiological system—the "lunasensor" system—evolved. It is assumed that it is a necessity to have a lunasensor as a particular variant of sensors of gravitation. [ABSTRACT FROM AUTHOR]

Older age is associated with functional declines throughout the body, including some aspects of cognitive performance. While dementia develops in only some elderly individuals, declines in cognitive functioning have an impact on daily living for many others. There are individual differences in age-related cognitive changes, however, and the factors that contribute to this variability have not been well-characterized. Recent evidence suggesting that age-related alterations in the endocrine environment may modulate cognitive changes has generated considerable interest. Currently, there is a discordance between the rapidly expanding number of studies of the possible neuroprotective effects of estrogens in postmenopausal women, and the relative dearth of analogous research on the putative effects of testosterone on cognitive and brain function in older men. This paper reviews the extant literature and reports new findings on the effects of testosterone loss and supplementation on cognitive and brain function in elderly men. Preliminary evidence suggests that testosterone loss may be a risk factor for cognitive decline and possibly for dementia. Conversely, the maintenance of higher testosterone levels either endogenously or through exogenous supplementation may prove beneficial for cognitive and brain function in elderly men. However, most studies are associational in nature and the intervention studies are of short-duration testosterone exposure in small samples of subjects. Large-scale placebo-controlled intervention studies are required to resolve ambiguities in the literature. Testosterone intervention to ameliorate cognitive decline may be warranted only when the efficacy and safety of longer-term use is firmly established. [ABSTRACT FROM AUTHOR]

Studies of autoimmune diseases have not yet elucidated why certain organs or vessels become the objects of injury while others are spared. This paper explores the hypothesis that important differences exist in regions of the aorta; these regional variations determine vulnerability to such diseases as atherosclerosis, aortitis, giant-cell arteritis, and Takayasu's disease. The reader is invited to reassess two issues: (1) whether the aorta is indeed a single homogeneous structure; and (2) whether the initial stage of aortitis (and indeed other diseases considered "autoimmune") may primarily be the result of acquired alterations of substrate that influence unique immune profiles, but that by themselves may not be pathogenic. Disease susceptibility and patterns are influenced by many factors that are either inborn or acquired. Examples include genetic background, gender, ethnicity, aging, prior and concomitant illnesses, habits, diet, and exposure to toxins and other environmental hazards. Studies of vascular diseases must assess how such variables affect regional anatomic differences in endothelial cells, subendothelial matrix, and vascular smooth muscle, as well as the response of each to a variety of stimuli. [ABSTRACT FROM AUTHOR]

The mammalian mitochondrial NADH dehydrogenase (complex I) is the major entry point for the electron transport chain. It is the largest and most complicated respiratory complex consisting of at least 46 subunits, 7 of which are encoded by mitochondrial DNA (mtDNA). Deficiency in complex I function has been associated with various human diseases including neurodegenerative diseases and the aging process. To explore ways to restore mitochondrial function in complex I-deficient cells, various cell models with mutations in genes encoding subunits for complex I have been established. In this paper, we discuss various approaches to recover mitochondrial activity, the complex I activity in particular, in cultured cells. [ABSTRACT FROM AUTHOR]

Cancer rates increase sharply with age in both sexes, and the majority of cases of cancer occur in patients over the age of 65 years. However, the incidence and mortality for cancer level off around 85-90 years of age, followed by a plateau, or even a decline in the last decades of life. Therefore, it seems reasonable to conclude that centenarians are endowed with a peculiar resistance to cancer. Tumor progression is a complex process that depends on interactions between tumor and host cells. One aspect of the host response, the inflammatory response, is of particular interest because it includes the release of proinflammatory cytokines, some of which may promote tumor growth and hence influence survival. Data in the literature reviewed in this paper suggest that some kind of solid tumors are affected by regulatory cytokine genotypes. In particular proinflammatory genotypes characterized by a low IL-10 producer or a high IL-6 producer seem to be associated with a worse clinical outcome. On the other hand, recent evidence has linked IL-10 and IL-6 cytokine polymorphisms to longevity. In fact, those individuals who are genetically predisposed to produce high levels of IL-6 have a reduced capacity to reach the extreme limits of human life, whereas the high IL-10-producer genotype is increased among centenarians. This opposite effect of IL-6 and IL-10 common gene polymorphisms in cancer and longevity is intriguing. These data prompt considerations of the role that antagonistic pleiotropy plays in disease and in longevity. Inflammatory genotypes may be both friends and enemies. In fact, they are an important and necessary part of the normal host responses to pathogens, but the overproduction of inflammatory cytokines might cause immune- inflammatory diseases and eventually death. In fact, our immune system has evolved to control pathogens, so proinflammatory responses are likely to be evolutionarily programmed to resist fatal infections, and a high IL-6 or a low IL-10 production is associated with increased resistance to pathogens. However, decreased level of IL-6 or increased level of IL-10 might better control inflammatory responses and cancer development. These conditions might result in an increased chance of long-life survival in an environment with a reduced antigen (i.e., pathogen) load. [ABSTRACT FROM AUTHOR]

Modification of proteins by reactive oxygen species is implicated in different disorders. The proteasome is a multicatalytic proteinase in charge of intracellular protein turnover and of oxidized proteins degradation. Consequently, proteasome function is very important in controlling the level of altered proteins in eukaryotic cells. Evidence for a decline in proteasome activity during skin photo-aging has been provided in Bulteau et al. in 2002. The ability of a lipid algae extract (Phaeodactylum tricornutum) to stimulate 20S proteasome peptidase activities was described by Nizard et al. in 2001. Furthermore, keratinocytes treated with Phaeodactylum tricornutum extract and then UVA and UVB irradiated, exhibited a sustained level of proteasome activity comparable to the one of nonirradiated cells. The level of modified proteins can be quantified by measurement of protein carbonyl content (Oxyblot technique), which has been shown to increase with aging and other disorders. In this paper, it is described that, in the presence of this lipid algae extract, the level of oxidized proteins is reduced, as assessed by the Oxyblot technique. These results are obtained both with culture of human keratinocytes and stratum corneum skin cells (obtained by stripping) from human volunteers. Altogether, these results argue for the presence of compounds in this algae extract that have a stimulating and/or protective effect on proteasome activity, resulting in a decreased level of protein oxidation. [ABSTRACT FROM AUTHOR]

Hearing impairment is considered a leading modifiable risk factor of cognitive decline and dementia. While most evidence has been established on clinical assessment of peripheral hearing loss, understanding of how central hearing in real‐world conditions is associated with cognitive aging is limited. This study analyzed the data of 473 unrelated healthy adults aged 36–100 years old from the Lifespan Human Connectome Project in Aging. Central hearing was evaluated using the Words‐in‐Noise decibel threshold. Cognitive functions were evaluated by the performance on cognitive tests, and cortical thickness was estimated from magnetic resonance imaging (MRI) data. Here, we show that a higher hearing threshold was associated with a lower performance on immediate and delayed episodic memory retrieval, switching aspect of executive function, working memory, reading decoding, and vocabulary comprehension. Cortical thickness in the left parahippocampal cortex (lPHC) was negatively associated with the hearing threshold and acted as a significant partial mediator in the association of central hearing with immediate recall, switching, reading decoding, and vocabulary comprehension. These findings suggest that cortical thickness in the lPHC, an early target of dementia, partially links central hearing and performance in multiple cognitive domains in aging. [ABSTRACT FROM AUTHOR]

Hearing abilities decline with age, and one of the most commonly reported hearing issues in older adults is a difficulty understanding speech when there is loud background noise. Understanding speech in noise relies on numerous cognitive processes, including working memory, and is supported by numerous brain regions, including the motor and motor planning systems. Indeed, many working memory processes are supported by motor and premotor cortical regions. Interestingly, lifelong musicians and nonmusicians given music training over the course of weeks or months show an improved ability to understand speech when there is loud background noise. These benefits are associated with enhanced working memory abilities, and enhanced activity in motor and premotor cortical regions. Accordingly, it is likely that music training improves the coupling between the auditory and motor systems and promotes plasticity in these regions and regions that feed into auditory/motor areas. This leads to an enhanced ability to dynamically process incoming acoustic information, and is likely the reason that musicians and those who receive laboratory‐based music training are better able to understand speech when there is background noise. Critically, these findings suggest that music‐based forms of auditory rehabilitation are possible and should focus on tasks that promote auditory–motor interactions. [ABSTRACT FROM AUTHOR]

Novelty anticipation activates the mesolimbic system and promotes subsequent long‐term memory in younger adults. Importantly, mesolimbic structures typically degenerate with age, which might reduce positive effects of novelty anticipation. Here, we used electroencephalography in combination with an established paradigm in healthy young (19–33 years old, n = 28) and older (53–84, n = 27) humans. Colored cues predicted the subsequent presentation of either a novel or previously familiarized image (75% cue validity). On the subsequent day, recognition memory for the novel images was tested. Behaviorally, novelty anticipation improved recollection‐based but not familiarity‐based recognition memory in both groups, and this effect was more pronounced in older subjects. Furthermore, novelty and familiarity cues increased theta (4–8 Hz) and decreased alpha/beta power (9–20 Hz); at outcome, expected novel and familiar images both increased beta power (13–25 Hz). Finally, a subsequent memory effect for expected novel images was associated with increases in beta power independent of age. Together, novelty anticipation drives hippocampus‐dependent long‐term recognition memory across the life span, and this effect appears to be related to neural beta oscillations. [ABSTRACT FROM AUTHOR]

This study aims to establish a biological age (BA) predictor and to investigate the roles of lifestyles on biological aging. The 14,848 participants with the available information of multisystem measurements from the Dongfeng–Tongji cohort were used to estimate BA. We developed a composite BA predictor showing a high correlation with chronological age (CA) (r = 0.82) by using an extreme gradient boosting (XGBoost) algorithm. The average frequency hearing threshold, forced expiratory volume in 1 second (FEV1), gender, systolic blood pressure, and homocysteine ranked as the top five important features for the BA predictor. Two aging indexes, recorded as the AgingAccel (the residual from regressing predicted age on CA) and aging rate (the ratio of predicted age to CA), showed positive associations with the risks of all‐cause (HR (95% CI) = 1.12 (1.10–1.14) and 1.08 (1.07–1.10), respectively) and cause‐specific (HRs ranged from 1.06 to ∼1.15) mortality. Each 1‐point increase in healthy lifestyle score (including normal body mass index, never smoking, moderate alcohol drinking, physically active, and sleep 7–9 h/night) was associated with a 0.21‐year decrease in the AgingAccel (95% CI: −0.27 to −0.15) and a 0.4% decrease in the aging rate (95% CI: −0.5% to −0.3%). This study developed a machine learning–based BA predictor in a prospective Chinese cohort. Adherence to healthy lifestyles showed associations with delayed biological aging, which highlights potential preventive interventions. [ABSTRACT FROM AUTHOR]

This study explores the association between age identity, perceptions of age, and health. It uses data from the first and second waves of the English Longitudinal Study of Ageing (ELSA). The sample consists of 8780 men and women. Four independent variables were used: perceptions of when middle age ends and old age starts, and the ages respondents would like to be and felt they were (desired and self-perceived ages). The outcomes variables were: self-assessed health, self-reported limiting long-standing illness or disability, hypertension, and diabetes. Statistical analysis included descriptive, bivariate, and multivariate tests. A series of logistic regression models were estimated, which were adjusted for age, sex, marital/cohabitation status, and socioeconomic position. The analysis showed that self-perceived age and perceived chronological end of middle age related to all four health outcomes over and above other covariates. In contrast, desired age did not relate to any of the outcomes, while perceived start of old age related only to self-reported health dimensions. These findings indicate the importance of age identity and age perceptions for health in old age. [ABSTRACT FROM AUTHOR]

Abstract: Telomere‐induced selection could take place if telomere‐associated disease risk shortens reproductive life span and differently reduces relative fitness among individuals. Some of these diseases first appear before reproductive senescence and could thus influence ongoing selection. We ask whether we can estimate the components of the breeder's equation for telomeres, in which the response to selection (R, by definition “evolution”) is the product of ongoing selection (S) and heritability (h2). However, telomere inheritance is a conundrum: in quantitative genetics, traits can usually be allocated to categories with relatively high or low heritability, depending on their association with relative fitness. Telomere traits, however, show wide variation in heritability from zero to one, across taxa, gender, ethnicity, age, and disease status. In spite of this, there is divergence in telomere length among populations, supporting past and ongoing telomere evolution. Rates of telomere attrition and elongation vary among taxa with some, but not complete, taxonomic coherence. For example, telomerase is commonly referred to as “restricted to the germ line in mammals,” but inbred mice and beavers have telomerase upregulation in somatic tissue, as do many ectotherms. These observations provoke a simplistic understanding of telomere evolutionary biology—clearly much is yet to be discovered. [ABSTRACT FROM AUTHOR]

Abstract: Extension of mammalian health and life span has been achieved using various dietary interventions. We previously reported that restricting dietary methionine (MET) content extends life span only when growth hormone signaling is intact (no life span increase in GH deficiency or GH resistance). To understand the metabolic responses of altered dietary MET in the context of accelerated aging (high GH), the current study evaluated MET and related pathways in short‐living GH transgenic (GH Tg) and wild‐type mice following 8 weeks of restricted (0.16%), low (0.43%), or enriched (1.3%) MET consumption. Liver MET metabolic enzymes were suppressed in GH Tg compared to diet‐matched wild‐type mice. MET metabolite levels were differentially affected by GH status and diet. SAM:SAH ratios were markedly higher in GH Tg mice. Glutathione levels were lower in both genotypes consuming 0.16% MET but reduced in GH Tg mice when compared to wild type. Tissue thioredoxin and glutaredoxin were impacted by diet and GH status. The responsiveness to the different MET diets is reflected across many metabolic pathways indicating the importance of GH signaling in the ability to discriminate dietary amino acid levels and alter metabolism and life span. [ABSTRACT FROM AUTHOR]

Abstract: Sulfur amino acids (SAAs) play numerous critical roles in metabolism and overall health maintenance. Preclinical studies have demonstrated that SAA‐restricted diets have many beneficial effects, including extending life span and preventing the development of a variety of diseases. Dietary sulfur amino acid restriction (SAAR) is characterized by chronic restrictions of methionine and cysteine but not calories and is associated with reductions in body weight, adiposity and oxidative stress, and metabolic changes in adipose tissue and liver resulting in enhanced insulin sensitivity and energy expenditure. SAAR‐induced changes in blood biomarkers include reductions in insulin, insulin‐like growth factor‐1, glucose, and leptin and increases in adiponectin and fibroblast growth factor 21. On the basis of these preclinical data, SAAR may also have similar benefits in humans. While little is known of the translational significance of SAAR, its potential feasibility in humans is supported by findings of its effectiveness in rodents, even when initiated in adult animals. To date, there have been no controlled feeding studies of SAAR in humans; however, there have been numerous relevant epidemiologic and disease‐based clinical investigations reported. Here, we summarize observations from these clinical investigations to provide insight into the potential effectiveness of SAAR for humans. [ABSTRACT FROM AUTHOR]

Abstract: The genomic hypomethylation hypothesis of aging proposes that an overall decrease in global DNA methylation occurs with age, and it has been argued that the decrease in global DNA methylation could be an important factor in aging, resulting in the relaxation of gene expression regulation and abnormal gene expression. Since it was initially observed that DNA methylation decreased with age in 1974, 16 articles have been published describing the effect of age on global DNA methylation in various tissues from rodents and humans. We critically reviewed the publications on the effect of age on DNA methylation and the expression of the enzymes involved in DNA methylation to evaluate the validity of the hypomethylation hypothesis of aging. On the basis of the current scientific literature, we conclude that a decrease in the global methylation of the genome occurs in most if not all tissues/cells as an animal ages. However, age‐related changes in DNA methylation in specific regions or at specific sites in the genome occur even though the global DNA methylation does not change. [ABSTRACT FROM AUTHOR]

It has long been known that aging, at both the cellular and organismal levels, contributes to the development and progression of the pathology of many chronic diseases. However, much less research has examined the inverse relationship-the contribution of chronic diseases and their treatments to the progression of aging-related phenotypes. Here, we discuss the impact of three chronic diseases (cancer, HIV/AIDS, and diabetes) and their treatments on aging, putative mechanisms by which these effects are mediated, and the open questions and future research directions required to understand the relationships between these diseases and aging. [ABSTRACT FROM AUTHOR]

Mindfulness meditation represents a mental training framework for cultivating the state of mindful awareness in daily life. Recently, there has been a surge of interest in how mindfulness meditation improves human health and well-being. Although studies have shown that mindfulness meditation can improve self-reported measures of disease symptomatology, the effect that mindfulness meditation has on biological mechanisms underlying human aging and disease is less clear. To address this issue, we conducted the first comprehensive review of randomized controlled trials examining the effects of mindfulness meditation on immune system parameters, with a specific focus on five outcomes: (1) circulating and stimulated inflammatory proteins, (2) cellular transcription factors and gene expression, (3) immune cell count, (4) immune cell aging, and (5) antibody response. This analysis revealed substantial heterogeneity across studies with respect to patient population, study design, and assay procedures. The findings suggest possible effects of mindfulness meditation on specific markers of inflammation, cell-mediated immunity, and biological aging, but these results are tentative and require further replication. On the basis of this analysis, we describe the limitations of existing work and suggest possible avenues for future research. Mindfulness meditation may be salutogenic for immune system dynamics, but additional work is needed to examine these effects. [ABSTRACT FROM AUTHOR]

Methionine restriction is a widely reported intervention for increasing life span in several model organisms. Low circulating levels of methionine are evident in the long-lived naked mole-rat, suggesting that it naturally presents with a life-extending phenotype akin to that observed in methionine-restricted animals. Similarly, long-lived dwarf mice also appear to have alteredmethionine metabolism. Themechanisms underlyingmethionine-restriction effects on life-span extension, however, remain unknown, as do their potential connections with caloric restriction, another well-established intervention for prolonging life span. Paradoxically, methionine is enriched in proteins expressed in mitochondria and may itself serve an important role in the detoxification of reactive oxygen species and may thereby contribute to delayed aging. Collectively, we highlight the evidence that modulation of the methionine metabolic network can extend life span-from yeast to humans-and explore the evidence that sulfur amino acids and the concomitant transsulfuration pathway play a privileged role in this regard. However, systematic studies in single organisms (particularly those that exhibit extreme longevity) are still required to distinguish the fundamental principles concerning the role of methionine and other amino acids in regulating life span. [ABSTRACT FROM AUTHOR]

After nearly a century of rigorous investigation and testing, dietary caloric restriction (CR) remains the most robust and reproducible method for slowing aging and maintaining health, function, and vitality. This intervention has been applied to species across the evolutionary spectrum, but for a number of reasons, practical applicability to humans has been questioned. To overcome these issues, we initiated the field of CR mimetics in 1998 and have observed its development into a full-fledged antiaging industry. Basically, strategies that enable individuals to obtain the biological benefits of CRwithout reducing actual food intake can be considered CR mimetics, whether functional, pharmaceutical, nutraceutical, or other. Some of the best known candidates include resveratrol and related agents, the antidiabetic drug metformin, and rapamycin and other mTOR regulators.While the mechanisms of action vary, these and essentially all CR mimetic candidates work through at least some of the same pathways as actual CR.While the entire field continues to evolve rapidly, the current status will be reviewed here, with particular focus on recent developments, the most practical relevance and applicability for potential consumers, and new strategies for the future. [ABSTRACT FROM AUTHOR]

The investigation of immune senescence has uncovered many changes in B cell development, maintenance, and function with increasing age. However, most of these studies have focused on conventional B cell subsets in the spleen. The B-1 cell subset is an essential arm of the innate immune system, which in general has been understudied in terms of immune senescence. Here, we review what is currently known about B cells during aging and go on to describe why B-1 cell biology is an important component of the aging immune system in the context of diseases that most affect the aged population. [ABSTRACT FROM AUTHOR]

The CD27+IgD+ B cell population, known as IgM memory, reduces with age. It is thought that this population is responsible for pneumococcal polysaccharide T-independent responses, and that the age-related reduction might be partially responsible for the increased susceptibility of older people to bacterial pathogens. There are other IgM+ B cell populations that do not express IgD. We compared the different IgM populations using high-throughput sequencing of the immunoglobulin (Ig) gene repertoire and multidimensional cell phenotyping and found that the different populations of IgM cells, defined by CD27 and IgD expression, have repertoire differences. Some of these differences are likely indicative of different selection pressures in an immune response, although the older individuals were found to have a changed repertoire in naive B cells, which may contribute to some of the changes seen in memory cells. In addition, even within the CD27+IgD+ IgM memory population there are multiple cell types. We show that the level of IgM expression varies substantially and hypothesize that this distinguishes between T-dependent and T-independent types of IgM memory cells. Significant age-related changes in the relative proportions of these populations may exacerbate the reduction in T-independent responders in old age. [ABSTRACT FROM AUTHOR]