National Institute on Aging Workshop: Repurposing Drugs or Dietary Supplements for Their Senolytic or Senomorphic Effects: Considerations for Clinical Trials.

Background: Cell senescence is implicated in numerous age-related conditions. Drugs and nutritional supplements developed for a variety of purposes kill senescent cells (senolytics) or suppress their secretions (senomorphics). There is interest in repurposing such drugs to treat or prevent age-related diseases.

Report: NIA Workshop on Measures of Physiologic Resiliencies in Human Aging.

Background/objectives: Resilience, the ability to resist or recover from adverse effects of a stressor, is of widespread interest in social, psychologic, biologic, and medical research and particularly salient as the capacity to respond to stressors becomes diminished with aging. To date, research on human resilience responses to and factors influencing these responses has been limited.

Methods: The National Institute on Aging convened a workshop in August 2015 on needs for research to improve measures to predict and assess resilience in human aging.

Advances in geroscience: impact on healthspan and chronic disease.

Population aging is unprecedented, without parallel in human history, and the 21st century will witness even more rapid aging than did the century just past. Improvements in public health and medicine are having a profound effect on population demographics worldwide. By 2017, there will be more people over the age of 65 than under age 5, and by 2050, two billion of the estimated nine billion people on Earth will be older than 60 (http://unfpa.

Skeletal muscle function deficit: a new terminology to embrace the evolving concepts of sarcopenia and age-related muscle dysfunction.

Background: Concerns remain as to the best terminology to embrace sarcopenia's evolving conceptualization. Many of these concerns stem from the fact that age-related decrements in muscle performance associated with physical impairment are only partially explained by decreases in muscle mass and that other pathophysiologic factors contribute to age-related impairments in muscle performance.

Methods: Review of literature on the evolving conceptualization of sarcopenia since its early definition in 1989 and concerns with terminology.

The Testosterone Trials: Seven coordinated trials of testosterone treatment in elderly men.

Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone concentrations due to known pituitary or testicular disease, and testosterone treatment improves the abnormalities. Prior studies of the effect of testosterone treatment in elderly men, however, have produced equivocal results.

Exceptional memory performance in the Long Life Family Study.

Research to understand variability at the highest end of the cognitive performance distribution has been scarce. Our aim was to define a cognitive endophenotype based on exceptional episodic memory (EM) performance and to investigate familial aggregation of EM in families from the Long Life Family Study (LLFS). Using a sample of 1911 nondemented offspring of long-lived probands, we created a quantitative phenotype, EM (memory z ≥ 1.

The Lifestyle Interventions and Independence for Elders Study: design and methods.

Background: As the number of older adults in the United States rises, maintaining functional independence among older Americans has emerged as a major clinical and public health priority. Older people who lose mobility are less likely to remain in the community; demonstrate higher rates of morbidity, mortality, and hospitalizations; and experience a poorer quality of life. Several studies have shown that regular physical activity improves functional limitations and intermediate functional outcomes, but definitive evidence showing that major mobility disability can be prevented is lacking.

Do gender, disability, and morbidity affect aging rate in the LLFS? Application of indices of cumulative deficits.

We used an approach of cumulative deficits to evaluate the rate of aging in 4954 participants of the Long-Life Family Study (LLFS) recruited in the U.S. (Boston, New York, and Pittsburgh) and Denmark.

Health and function of participants in the Long Life Family Study: A comparison with other cohorts.

Individuals from families recruited for the Long Life Family Study (LLFS) (n= 4559) were examined and compared to individuals from other cohorts to determine whether the recruitment targeting longevity resulted in a cohort of individuals with better health and function. Other cohorts with similar data included the Cardiovascular Health Study, the Framingham Heart Study, and the New England Centenarian Study. Diabetes, chronic pulmonary disease and peripheral artery disease tended to be less common in LLFS probands and offspring compared to similar aged persons in the other cohorts.

Toward an integrated research agenda for critical illness in aging.

Aging brings an increased predisposition to critical illness. Patients older than 65 years of age account for approximately half of all intensive care unit (ICU) admissions in the United States, a proportion that is expected to increase considerably with the aging of the population. Emerging research suggests that elderly survivors of intensive care suffer significant long-term sequelae, including accelerated age-related functional decline.

"Predicting" parental longevity from offspring endophenotypes: data from the Long Life Family Study (LLFS).

While there is evidence that longevity runs in families, the study of long-lived families is complicated by the fact that longevity-related information is available only for the oldest old, many of whom may be deceased and unavailable for testing, and information on other living family members, primarily descendents, is censored. This situation requires a creative approach for analyzing determinants of longevity in families. There are likely biomarkers that predict an individual's longevity, suggesting the possibility that those biomarkers which are heritable may constitute valuable endophenotypes for exceptional survival.

A family longevity selection score: ranking sibships by their longevity, size, and availability for study.

Family studies of exceptional longevity can potentially identify genetic and other factors contributing to long life and healthy aging. Although such studies seek families that are exceptionally long lived, they also need living members who can provide DNA and phenotype information. On the basis of these considerations, the authors developed a metric to rank families for selection into a family study of longevity.

Prospects for life span extension.

Life expectancy has increased dramatically in the United States and in much of the world in recent years and decades. The factors underlying this increase are incompletely understood and are undoubtedly complex. A question that drives current research is whether life expectancy can be further extended using current knowledge of modifiable risk factors.

Validation study of energy expenditure and intake during calorie restriction using doubly labeled water and changes in body composition.

Background: Clinical trials involving calorie restriction (CR) require an assessment of adherence to a prescribed CR with the use of an objective measure of energy intake (EI).

Objective: The objective was to validate the use of energy expenditure (EE) measured by doubly labeled water (DLW), in conjunction with precise measures of body composition, to calculate an individual's EI during 30% CR.

Design: Ten participants underwent 30% CR for 3 wk.

Effects of a physical activity intervention on measures of physical performance: Results of the lifestyle interventions and independence for Elders Pilot (LIFE-P) study.

Background: The Short Physical Performance Battery (SPPB), which includes walking, balance, and chair stands tests, independently predicts mobility disability and activities of daily living disability. To date, however, there is no definitive evidence from randomized controlled trials that SPPB scores can be improved. Our objective was to assess the effect of a comprehensive physical activity (PA) intervention on the SPPB and other physical performance measures.

Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults.

Evolving definitions of frailty, and improved understanding of molecular and physiological declines in multiple systems that may increase vulnerability in frail, older adults has encouraged investigators from many disciplines to contribute to this emerging field of research. This article reports on the results of the 2004 American Geriatrics Society/National Institute on Aging conference on a Research Agenda on Frailty in Older Adults, which brought together a diverse group of clinical and basic scientists to encourage further investigation in this area. This conference was primarily focused on physical and physiological aspects of frailty.

From bedside to bench: research agenda for frailty.

The American Geriatrics Society sponsored a working conference in January 2004, funded by the National Institute on Aging, to establish the state of the art in frailty research and to set a research agenda for the future. The invited participants included senior basic biologists, epidemiologists, geneticists, and clinical investigators who study aging-related issues. This article summarizes the central theoretical observations on frailty and research needs and opportunities presented and discussed at this conference, and lays out an agenda for future research on frailty.

The lifestyle interventions and independence for elders (LIFE) pilot study: design and methods.

The LIFE study is a multicenter pilot for a proposed full scale, two-arm randomized controlled trial that will contrast the effect of a physical activity intervention with a successful aging education program on the occurrence of incident major mobility disability (the inability to complete a 400 m walk) or death in at-risk sedentary older adults. Four hundred older adults from 4 clinical sites will be recruited for this purpose. All participants will be followed for at least 1-year; however, we will continue to follow all participants until the final randomized individual has reached the 1-year mark.

The future of aging therapies.

Advances in understanding aging processes and their consequences are leading to the development of therapies to slow or reverse adverse changes formerly considered to be "normal" aging and processes that underlie multiple age-related conditions. Estimating the effectiveness of candidate aging therapies, whose effects on human aging may require many years to determine, is a particular challenge. Strategies for identifying candidate interventions can be developed through multiple approaches, including the screening of molecular targets and pathways in vitro and in animal models, informed as well by evidence from human genetic and epidemiologic data.