Quantification of biological aging in young adults

Antiaging therapies show promise in model organism research. Translation to humans is needed to address the challenges of an aging global population. Interventions to slow human aging will need to be applied to still-young individuals. However, most human aging research examines older adults, many with chronic disease. As a result, little is known about aging in young humans. We studied aging in 954 young humans, the Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades of life. We developed and validated two methods by which aging can be measured in young adults, one cross-sectional and one longitudinal. Our longitudinal measure allows quantification of the pace of coordinated physiological deterioration across multiple organ systems (e.g., pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function). We applied these methods to assess biological aging in young humans who had not yet developed age-related diseases. Young individuals of the same chronological age varied in their “biological aging” (declining integrity of multiple organ systems). Already, before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline and brain aging, self-reported worse health, and looked older. Measured biological aging in young adults can be used to identify causes of aging and evaluate rejuvenation therapies.By 2050, the world population aged 80 y and above will more than triple, approaching 400 million individuals (1, 2). As the population ages, the global burden of disease and disability is rising (3). From the fifth decade of life, advancing age is associated with an exponential increase in burden from many different chronic conditions (Fig. 1). The most effective means to reduce disease burden and control costs is to delay this progression by extending healthspan, years of life lived free of disease and disability (4). A key to extending healthspan is addressing the problem of aging itself (5–8).Open in a separate windowFig. 1.Burden of chronic disease rises exponentially with age. To examine the association between age and disease burden, we accessed data from the Institute for Health Metrics and Evaluation Global Burden of Disease database (www.healthdata.org/gbd) (43). Data graph (A) disability-adjusted life years (DALYs) and (B) deaths per 100,000 population by age. Bars, from bottom to top, reflect the burden of cardiovascular disease (navy), type-2 diabetes (light blue), stroke (lavender), chronic respiratory disease (red), and neurological disorders (purple).At present, much research on aging is being carried out with animals and older humans. Paradoxically, these seemingly sensible strategies pose translational difficulties. The difficulty with studying aging in old humans is that many of them already have age-related diseases (9–11). Age-related changes to physiology accumulate from early life, affecting organ systems years before disease diagnosis (12–15). Thus, intervention to reverse or delay the march toward age-related diseases must be scheduled while people are still young (16). Early interventions to slow aging can be tested in model organisms (17, 18). The difficulty with these nonhuman models is that they do not typically capture the complex multifactorial risks and exposures that shape human aging. Moreover, whereas animals’ brief lives make it feasible to study animal aging in the laboratory, humans’ lives span many years. A solution is to study human aging in the first half of the life course, when individuals are starting to diverge in their aging trajectories, before most diseases (and regimens to manage them) become established. The main obstacle to studying aging before old age—and before the onset of age-related diseases—is the absence of methods to quantify the Pace of Aging in young humans.We studied aging in a population-representative 1972–1973 birth cohort of 1,037 young adults followed from birth to age 38 y with 95% retention: the Dunedin Study (SI Appendix). When they were 38 y old, we examined their physiologies to test whether this young population would show evidence of individual variation in aging despite remaining free of age-related disease. We next tested the hypothesis that cohort members with “older” physiologies at age 38 had actually been aging faster than their same chronologically aged peers who retained “younger” physiologies; specifically, we tested whether indicators of the integrity of their cardiovascular, metabolic, and immune systems, their kidneys, livers, gums, and lungs, and their DNA had deteriorated more rapidly according to measurements taken repeatedly since a baseline 12 y earlier at age 26. We further tested whether, by midlife, young adults who were aging more rapidly already exhibited deficits in their physical functioning, showed signs of early cognitive decline, and looked older to independent observers.     

Feeling older and wanting to be younger

Two samples of middle-aged women were compared using a questionnaire adapted from Rossi (1980). One sample (N = 20) consisted of women who felt older than and desired to be younger than their own age. The second sample (N = 19) was comprised of women who felt and desired to be their own age. Statistically significant differences between the groups were that women who felt older reported more physical changes of aging, less satisfaction with their life context, and more worries than the women who felt their chronological age. Results of this study suggest that current life stress contributes to middle-aged women's perceptions of feeling older and desiring to be younger than their own age.Revision of a paper presented at the 86th Annual American Anthropological Association Meetings, Chicago, IL, November 21, 1987. The project was supported in whole or in part by Division of Nursing, Public Health Service Grant NIH 5R21 NU00839 — Awarded to the University of Michigan School of Nursing.     

Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands

The insulin/insulin-like growth factor-like signaling pathway, present in all multicellular organisms, regulates diverse functions including growth, development, fecundity, metabolic homeostasis, and lifespan. In flies, ligands of the insulin/insulin-like growth factor-like signaling pathway, the Drosophila insulin-like peptides, regulate growth and hemolymph carbohydrate homeostasis during development and are expressed in a stage- and tissue-specific manner. Here, we show that ablation of Drosophila insulin-like peptide-producing median neurosecretory cells in the brain leads to increased fasting glucose levels in the hemolymph of adults similar to that found in diabetic mammals. They also exhibit increased storage of lipid and carbohydrate, reduced fecundity, and reduced tolerance of heat and cold. However, the ablated flies show an extension of median and maximal lifespan and increased resistance to oxidative stress and starvation.     

Older Adults' Views of “Successful Aging”—How Do They Compare with Researchers' Definitions?

OBJECTIVES: To determine whether older adults have thought about aging and aging successfully and to compare their perceptions of successful aging with attributes of successful aging identified in the published literature. DESIGN: A cross-sectional, mailed survey. SETTING: King County, Washington. PARTICIPANTS: Nondemented participants from two cohorts. The first cohort, referred to as Kame, which means turtle, a symbol of longevity for Japanese, enrolled 1,985 Japanese Americans aged 65 and older and was established in 1992-94. The second cohort, Adult Changes in Thought, enrolled 2,581 white men and women aged 65 and older from a health maintenance organization and was established in 1994-96. MEASUREMENTS: Respondents were asked whether they had ever thought about aging and aging successfully and whether these thoughts had changed over the previous 20 years and about how important specific attributes, originating from the published literature, were in characterizing successful aging. RESULTS: Overall, 90% had previously thought about aging and aging successfully, and approximately 60% said their thoughts had changed over the previous 20 years. The Japanese-American group rated 13 attributes as important to successful aging; the white group rated the same 13 as important and added one additional attribute, learning new things. CONCLUSION: Older adults' definition of successful aging is multidimensional, encompassing physical, functional, psychological, and social health. In contrast, none of the published work describing attributes of successful aging includes all four dimensions. Future work would benefit from an expanded definition to adequately reflect the perceptions of older adults.     

Lipofuscin in lymphocytes and plasma cells in aging

The age-related changes in spleen and lymph node lymphocytes and plasma cells of Wistar rats and in the peripheral lymphocytes of healthy human individuals were examined. Similar changes were described in human and rat lymphocytes and plasma cells consisting of mitochondrial lesions. The cristae of the mitochondria disappeared and were replaced by myelin-like structure, lamellar structure, electron-dense and electron-translucent material. It is supposed that this material corresponds to lipofuscin.     

Childless elderly: Theoretical perspectives and practical concerns

Almost nothing is concretely known about childless elderly in cross-cultural perspective. Few published papers have appeared on this social category in the West, although childless elders make up (at least) 20% of the population of elderly in many Western nations. Little is known about childless elderly in the Third World. This paper provides some theoretical background to the study of childless elderly and articulates some social policy concerns about them. It suggests that there are five important questions to examine concerning the lives of childless elderly. These include, how childless aged are or are not provided for in societies in which a great deal of the care of the aged is undertaken by children; how kinship functions as a matrix for care; how the increasingly common phenomenon of voluntary childless may give meaning to childlessness in late life; how childlessness fits with such social science models such as the developmental cycle; and, the relationship of this phenomenon to changing opportunities for women. The paper further examines how factors such as fertility, systems of caregiving, the social meaning of childlessness, alternatives to childlessness such as adoption, and educational and economic opportunities may affect the lives of childless elders.     

The skin as a mirror of the aging process in the human organism--state of the art and results of the aging research in the German National Genome Research Network 2 (NGFN-2)

As our society is growing older, the consequences of aging have begun to gain particular attention. Improvement of quality of life at old age and prevention of age-associated diseases have become the main focus of the aging research. The process of aging in humans is complex and underlies multiple influences, with the probable involvement of heritable and various environmental factors. In particular, hormones are decisively involved in the generation of aging. Over time, important circulating hormones decline due to a reduced secretion of the pituitary, the adrenal glands and the gonads or due to an intercurrent disease. Among them, serum levels of growth factors and sexual steroids show significant aging-associated changes. Within the scope of the Explorative Project 'Genetic aetiology of human longevity' supported by the German National Genome Research Network 2 (NGFN-2) an in vitro model of human hormonal aging has been developed. Human SZ95 sebocytes were maintained under a hormone-substituted environment consisting of growth factors and sexual steroids in concentrations corresponding to those circulating in 20- and in 60-year-old women. Eight hundred and ninety-nine genes showed a differential expression in SZ95 sebocytes maintained under the 20- and 60-year-old hormone mixture, respectively. Among them genes were regulated which are involved in biological processes which are all hallmarks of aging. The most significantly altered signaling pathway identified was that of the transforming growth factor-beta (TGF-beta). A disturbed function of this cascade has been associated with tumorigenesis, i.e. in pancreatic, prostate, intestine, breast, and uterine cancer. Interestingly, genes expressed in signaling pathways operative in age-associated diseases such as Huntington's disease (HD), dentatorubral-pallidoluysian atrophy (DRPLA), and amyotrophic lateral sclerosis (ALS) were also identified. These data demonstrate that skin and its appendages may represent an adequate model for aging research. Hormones interact in a complex fashion, and aging may be partly attributed to the changes in their circulating blood levels. Furthermore, a disturbed hormone status may partially act towards the manifestation of neurodegenerative diseases. Thus, these results could be a basis for an integrated and interdisciplinary approach to the analysis of the aging process.     

Failing to Focus on Healthy Aging: A Frailty of Our Discipline?

The academic geriatrics community has provided outstanding leadership in addressing frailty and complexity in older adults, but a minority of older adults are frail. Although resources to treat older adults are limited, and it is appropriate to focus clinical efforts on those with frailty and multimorbidity, there is also important expertise that can be brought to bear on the health of ALL older adults. A review of the literature suggests that attention to healthy or successful aging has failed to keep pace with the focus on frailty. By providing leadership to promote successful aging, the quality of life of older adults across the spectrum can be improved and transitions to frailty reduced. The template that leaders have established in understanding frailty—defining and operationalizing it, understanding outcomes, identifying pathophysiology—can be used as an approach to successful aging. Several community‐based programs have been successful in promoting successful aging. These are potentially highly scalable and could have a substantial effect on the aging population, but their essential components need to be better understood. The geriatrics community is uniquely positioned to take on this role. This is a critical time to work together to make the lives of all older adults as healthy and fulfilling as possible.     

Age-dependent and age-independent human memory persistence is enhanced by delayed posttraining methylphenidate administration

Healthy human volunteers 16–82 years of age with at least 10 years of schooling were exposed to two different memory tasks. The first task involved incidental memory. The subjects were asked, as casually as possible: “Did you watch any movie on TV 2 days ago? And 7 days ago? If so, do you remember the title of the movie(s) and the name of the first two actors (actresses)?” Retention scores (maximum = 3: title, actor 1, and actor 2) were equally high (overall mean = 2.6, n = 61) in all age groups (16–20, 21–30, 31–40, 41–60, and 61–82 years) for the day 2 scores. Scores for the movie seen 7 days before decreased significantly and progressively in the three older groups in relation to age, which indicates reduced persistence of this type of memory beginning at the age of 41–50 years and becoming more extensive over the years. The other task was a formal memory procedure. Subjects were asked to study a brief text with factual information on the 1954 World Soccer Cup for 10 min. They were then exposed to 10 questions on the text 2 days and, again, 7 days later. Retention scores declined between the two tests, but in this task, the decline of persistence occurred to a similar extent in all age groups, and thus was not dependent on age. Methylphenidate (10 mg p.o.) given 12 hours after acquisition markedly enhanced persistence of the two memory types. This suggests an involvement of dopaminergic processes in persistence in the late posttraining period.