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.

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.

Zeno's Paradox of Immortality.

Scientists who speculate on the future of human longevity have a broad range of views ranging from the promise of immortality, to radical life extension, to declines in life expectancy. Among those who contend that radical life extension is already here, or on the horizon, or immortality is forthcoming, elements of their reasoning appear surprisingly close, if not identical, to a famous mathematical paradox posed by the ancient Greek mathematician known as Zeno. Here we examine the underlying assumptions behind the views that much longer life expectancies are forthcoming or have already arrived, and place their line of reasoning within the context of a new Zeno paradox described here as The Paradox of Immortality.

Science fact versus SENS foreseeable.

Scientists in the various fields of aging share a common goal--the extension of healthy life. However, claiming that the only way to accomplish this is to treat the complications of aging rather than its causes requires more than declarations made by proponents of SENS--it requires empirical research based on the scientific method. As this paper illustrates, it will be difficult to prove that SENS interventions work because the primary result of interest, negligible senescence, is not an outcome variable in empirical tests of SENS.

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.

Aging in America in the twenty-first century: demographic forecasts from the MacArthur Foundation Research Network on an Aging Society.

CONTEXT: The aging of the baby boom generation, the extension of life, and progressive increases in disability-free life expectancy have generated a dramatic demographic transition in the United States. Official government forecasts may, however, have inadvertently underestimated life expectancy, which would have major policy implications, since small differences in forecasts of life expectancy produce very large differences in the number of people surviving to an older age. This article presents a new set of population and life expectancy forecasts for the United States, focusing on transitions that will take place by midcentury. METHODS: Forecasts were made with a cohort-components methodology, based on the premise that the risk of death will be influenced in the coming decades by accelerated advances in biomedical technology that either delay the onset and age progression of major fatal diseases or that slow the aging process itself. FINDINGS: Results indicate that the current forecasts of the U.S. Social Security Administration and U.S. Census Bureau may underestimate the rise in life expectancy at birth for men and women combined, by 2050, from 3.1 to 7.9 years. CONCLUSIONS: The cumulative outlays for Medicare and Social Security could be higher by $3.2 to $8.3 trillion relative to current government forecasts. This article discusses the implications of these results regarding the benefits and costs of an aging society and the prospect that health disparities could attenuate some of these changes.

The benefits of risk factor prevention in Americans aged 51 years and older.

OBJECTIVES: We assessed the potential health and economic benefits of reducing common risk factors in older Americans. METHODS: A dynamic simulation model tracked a national cohort of persons 51 and 52 years of age to project their health and medical spending in prevention scenarios for diabetes, hypertension, obesity, and smoking. RESULTS: The gain in life span from successful treatment of a person aged 51 or 52 years for obesity would be 0.85 years; for hypertension, 2.05 years; and for diabetes, 3.17 years. A 51- or 52-year-old person who quit smoking would gain 3.44 years. Despite living longer, those successfully treated for obesity, hypertension, or diabetes would have lower lifetime medical spending, exclusive of prevention costs. Smoking cessation would lead to increased lifetime spending. We used traditional valuations for a life-year to calculate that successful treatments would be worth, per capita, $198,018 (diabetes), $137,964 (hypertension), $118,946 (smoking), and $51,750 (obesity). CONCLUSIONS: Effective prevention could substantially improve the health of older Americans, and--despite increases in longevity--such benefits could be achieved with little or no additional lifetime medical spending.

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.

A potential decline in life expectancy in the United States in the 21st century.

Forecasts of life expectancy are an important component of public policy that influence age-based entitlement programs such as Social Security and Medicare. Although the Social Security Administration recently raised its estimates of how long Americans are going to live in the 21st century, current trends in obesity in the United States suggest that these estimates may not be accurate. From our analysis of the effect of obesity on longevity, we conclude that the steady rise in life expectancy during the past two centuries may soon come to an end.

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.

Pursuing the longevity dividend: scientific goals for an aging world.

The aging of humanity is about to experience a radical change as the demographic transformation to an older world is approaching its final stage. In recent decades, scientists have learned enough about the biological aging processes that many believe it will become possible to slow aging in humans. We contend that the social, economic, and health benefits that would result from such advances may be thought of as "longevity dividends," and that they should be aggressively pursued as the new approach to health promotion and disease prevention in the 21st century. The time has arrived for governments and national and international healthcare organizations to make research into healthy aging a major research priority.

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.