Geroscience and Its Promise.

Why we age and whether our lifespan can be extended have intrigued scientists for centuries. Meanwhile public health advances mean humanity is having to confront the realities of an aging and increasingly frail population. The nascent field of geroscience offers hope that healthspan not just lifespan can be extended. It has spawned a vibrant scientific community that includes researchers studying fundamental biology, translational approaches, economics, and research funding. The knowledge gained from work in this area has the potential to influence the lives of most people alive today.

Personalized Financial Planning Using Applied Genetics.

Forthcoming advances in geroscience will influence the health span of current and future generations and generate both challenges and opportunities for those approaching or reaching retirement ages. The resulting changes in the life course will influence those reaching stages in life that are commonly associated with retirement. How people plan for that later phase of life is critical-especially given that current approaches to planning are either nonexistent or outdated. In this review, we show how advances in applied genetics can yield valuable information for individuals that are facing the challenges and opportunities that will accompany anticipated advances in geroscience and their unique influence on the life span and health span of current and future generations.

From Life Span to Health Span: Declaring "Victory" in the Pursuit of Human Longevity.

A difficult dilemma has presented itself in the current era. Modern medicine and advances in the medical sciences are tightly focused on a quest to find ways to extend life-without considering either the consequences of success or the best way to pursue it. From the perspective of physicians treating their patients, it makes sense to help them overcome immediate health challenges, but further life extension in increasingly more aged bodies will expose the saved population to an elevated risk of even more disabling health conditions associated with aging. Extended survival brought forth by innovations designed to treat diseases will likely push more people into a "red zone"-a later phase in life when the risk of frailty and disability rises exponentially. The inescapable conclusion from these observations is that life extension should no longer be the primary goal of medicine when applied to long-lived populations. The principal outcome and most important metric of success should be the extension of health span, and the technological advances described herein that are most likely to make the extension of healthy life possible.

Moving geroscience from the bench to clinical care and health policy.

Geriatricians and others must embrace the emerging field of geroscience. Until recently geroscience research was pursued in laboratory animals, but now this field requires specialized expertise in the care of vulnerable older patients with multiple chronic diseases and geriatric syndromes, the population likely to benefit the most from emerging therapies. While chronological aging measures the inevitable passage of clock time that occurs equally for everyone, biological aging varies among individuals, and importantly, it is modifiable. Advances in our understanding of biological aging, the discovery of strategies for modifying its rate, and an appreciation of aging as a shared risk factor for chronic diseases have jointly led to the Geroscience Hypothesis. This hypothesis states that interventions modifying aging biology can slow its progression-resulting in the delay or prevention of the onset of multiple diseases and disorders. Here we wish to report on the Third Geroscience Summit held at National Institutes of Health on November 4-5, 2019, which highlighted the importance of engaging other disciplines including clinicians. Involvement by scientists with expertise in clinical trials, health outcomes research, behavioral and social sciences, health policy, and economics is urgently needed to translate geroscience discoveries from the bench to clinical care and health policy. Adding to the urgency of broadening this geroscience coalition is the emergence of biological aging as one the most important modifiable factors of COVID-19, combined with the inability of our society to once again recognize and confront aging as a priority and opportunity when facing these types of public health emergencies.

Inconvenient Truths About Human Longevity.

The rise in human longevity is one of humanity's crowning achievements. Although advances in public health beginning in the 19th century initiated the rise in life expectancy, recent gains have been achieved by reducing death rates at middle and older ages. A debate about the future course of life expectancy has been ongoing for the last quarter century. Some suggest that historical trends in longevity will continue and radical life extension is either visible on the near horizon or it has already arrived; whereas others suggest there are biologically based limits to duration of life, and those limits are being approached now. In "inconvenient truths about human longevity" we lay out the line of reasoning and evidence for why there are limits to human longevity; why predictions of radical life extension are unlikely to be forthcoming; why health extension should supplant life extension as the primary goal of medicine and public health; and why promoting advances in aging biology may allow humanity to break through biological barriers that influence both life span and health span, allowing for a welcome extension of the period of healthy life, a compression of morbidity, but only a marginal further increase in life expectancy.

Aging and drug discovery.

Multiple interventions in the aging process have been discovered to extend the healthspan of model organisms. Both industry and academia are therefore exploring possible transformative molecules that target aging and age-associated diseases. In this overview, we summarize the presented talks and discussion points of the 5th Annual Aging and Drug Discovery Forum 2018 in Basel, Switzerland. Here academia and industry came together, to discuss the latest progress and issues in aging research. The meeting covered talks about the mechanistic cause of aging, how longevity signatures may be highly conserved, emerging biomarkers of aging, possible interventions in the aging process and the use of artificial intelligence for aging research and drug discovery. Importantly, a consensus is emerging both in industry and academia, that molecules able to intervene in the aging process may contain the potential to transform both societies and healthcare.

Primary Prevention with a Capital P.

The survival of large segments of human populations to advanced ages is a crowning achievement of improvements in public health and medicine, but in the 21st century, our continued desire to extend life brings forth a unique dilemma. The risk of death from chronic fatal diseases has declined, but even if it continues to do so in the future, the resulting longevity benefits are likely to diminish. It is even possible that unhealthy life expectancy could rise in the future as major fatal diseases wane. The reason for this is that the longer we live, the greater the influence of biological aging on the expression of fatal and disabling diseases. Research in gerontology has already demonstrated that aging is inherently modifiable, and that a therapeutic intervention that slows aging in people is a plausible target for science and public health. Given the speed with which population aging is progressing and chronic fatal and disabling conditions are challenging health-care costs across the globe, the case is now being made that delayed aging could be one of the most efficient and promising ways to combat disease, extend healthy life, compress morbidity, and reduce health-care costs.

Articulating the Case for the Longevity Dividend.

The survival of large segments of human populations to advanced ages is a crowning achievement of improvements in public health and medicine. But, in the 21st century, our continued desire to extend life brings forth a unique dilemma. The risk of death from cardiovascular diseases and many forms of cancer have declined, but even if they continue to do so in the future, the resulting health benefits and enhanced longevities are likely to diminish. It is even possible that healthy life expectancy could decline in the future as major fatal diseases wane. The reason is that the longer we live, the greater is the influence of biological aging on the expression of fatal and disabling diseases. As long as the rates of aging of our bodies continues without amelioration, the progress we make on all major disease fronts must eventually face a point of diminishing returns. Research in the scientific study of aging has already showed that the aging of our bodies is inherently modifiable, and that a therapeutic intervention that slows aging in people is a plausible target for science and public health. Given the speed with which population aging is progressing and chronic fatal and disabling conditions are challenging health care costs across the globe, the case is now being made in the scientific literature that delayed aging could be one of the most efficient and promising ways to combat disease, extend healthy life, compress morbidity, and reduce health care costs. A consortium of scientists and nonprofit organizations has devised a plan to initiate an accelerated program of scientific research to develop, test for safety and efficacy, and then disseminate a therapeutic intervention to delay aging if proven to be safe and effective; this is referred to as the Longevity Dividend Initiative Consortium (LDIC). In this review, I articulate the case for the LDIC.

Preparing for an Aging World: Engaging Biogerontologists, Geriatricians, and the Society.

Although the demographic revolution has produced hundreds of millions people aged 65 and older, a substantial segment of that population is not enjoying the benefits of extended healthspan. Many live with multiple chronic conditions and disabilities that erode the quality of life. The consequences are also costly for society. In the United States, the most costly 5% of Medicare beneficiaries account for approximately 50% of Medicare's expenditures. This perspective summarizes a recent workshop on biomedical approaches to best extend healthspan as way to reduce age-related dysfunction and disability. We further specify the action items necessary to unite health professionals, scientists, and the society to partner around the exciting and palpable opportunities to extend healthspan.

Has the Rate of Human Aging Already Been Modified?

In recent years, three hypotheses have been set forth positing variations on a common question-Has the rate of human aging already been modified? There is no disputing that people now live longer than ever before in history, and considerable variation in duration of life persists as a fundamental attribute of human longevity, but are these events caused by a measurable and verifiable difference in the rate at which people age, or are there other reasons why they occur? In this article, I explore the historical record involving changes in survival and life expectancy at older ages dating back to 1900, and examine what factors will likely contribute to changes in longevity in the United States through 2040. Evidence suggests that despite the absence of verifiable metrics of biological age, delayed aging is unlikely to be a cause of secular increases in life expectancy, but it could explain variation in survival among population subgroups, and it is the most likely explanation for why exceptionally long-lived people experience less disease and live longer than the rest of the population. If genetic heterogeneity explains any significant part of current variation in longevity, this opens the door to the development of therapeutic interventions that confer these advantages to the rest of the population.

Heterogeneity in healthy aging.

For a surprisingly large segment of the older population, chronological age is not a relevant marker for understanding, measuring, or experiencing healthy aging. Using the 2003 Medical Expenditure Panel Survey and the 2004 Health and Retirement Study to examine the proportion of Americans exhibiting five markers of health and the variation in health-related quality of life across each of eight age groups, we find that a significant proportion of older Americans is healthy within every age group beginning at age 51, including among those aged 85+. For example, 48% of those aged 51-54 and 28% of those aged 85+ have excellent or very good self-reported health status; similarly, 89% of those aged 51-54 and 56% of those aged 85+ report no health-based limitations in work or housework. Also, health-related quality of life ranges widely within every age group, yet there is only a comparatively small variation in median quality of life across age groups, suggesting that older Americans today may be experiencing substantially different age-health trajectories than their predecessors. Patterns are similar for medical expenditures. Several policy implications are explored.

Substantial health and economic returns from delayed aging may warrant a new focus for medical research.

Recent scientific advances suggest that slowing the aging process (senescence) is now a realistic goal. Yet most medical research remains focused on combating individual diseases. Using the Future Elderly Model--a microsimulation of the future health and spending of older Americans--we compared optimistic "disease specific" scenarios with a hypothetical "delayed aging" scenario in terms of the scenarios' impact on longevity, disability, and major entitlement program costs. Delayed aging could increase life expectancy by an additional 2.2 years, most of which would be spent in good health. The economic value of delayed aging is estimated to be $7.1 trillion over fifty years. In contrast, addressing heart disease and cancer separately would yield diminishing improvements in health and longevity by 2060--mainly due to competing risks. Delayed aging would greatly increase entitlement outlays, especially for Social Security. However, these changes could be offset by increasing the Medicare eligibility age and the normal retirement age for Social Security. Overall, greater investment in research to delay aging appears to be a highly efficient way to forestall disease, extend healthy life, and improve public health.

Can a lot more people live to one hundred and what if they did?

In the 21st century humanity will witness unprecedented, increases in the number of older people, especially centenarians, in both the developed and developing world. From a public policy standpoint, the aging of our populations and the longer lives we experience will change, the fabric of our modern world - from the funding of age entitlement programs, to the rising cost of health care, to the new ways in which we transport ourselves in increasingly more urban environments. If it becomes possible for biomedical advances to manufacture a form of biological plasticity among the new generations reaching 85 and older in the future, much like that which now exists for the recent middle-aged classes of people aged 65-85, then the future of aging will be bright. If we fail to marshal resources to confront the biological processes of aging, then it is possible that the more destructive side of senescence will emerge. In this paper, I explore the various perspectives on the future course of longevity, examine the prospects for significant increases in the number of very old people - especially centenarians - and present a general view of the demographic aging of our changing society.