Healthy Longevity: An Introduction to the Special Issue

Across the world, more people are living longer. Yet as Victor Dzau and Jo Ann Jenkins point out in their editorial, “whether the extra years will be good ones—and whether societies and economies will benefit as a result–depends on the actions we take now” (1). This special issue of the Journals of Gerontology Series A: Biological and Medical Sciences examines enablers of healthy longevity as well as the accompanying opportunities and challenges. Framing this conversation are two articles about human life span. In defending the veracity of the well-publicized 122-year life of Frenchwoman Jeanne Calment’s age at death, Jean-Marie Robine and coauthors define the current human life span (2). A highly publicized theory challenging Jeanne Calment’s age claim was based in part upon the ageist contention that she “didn’t look frail enough to be a supercentenarian.” One of many consistent forms of evidence supporting the claim of a 122-year life is the finding that photos of Jeanne Calment in her tenth and part of her 11th decades of life correlate with real-time descriptions of her remarkable functional status at those ages. Both her appearance and independent function for the vast majority of her extremely long life are consistent with what must have been a relatively slow biological process of aging and increased resistance to aging-related diseases and syndromes. This prolongation of good health and function is consistent with James Fries’ theory of “compression of morbidity hypothesis,” which states that as one approaches the limit of life span, long-lived individuals must necessarily compress the period of time in which they experience diseases associated with increased mortality towards the end of their life (3). In the second article, Jay Olshansky and Bruce Carnes argue that although humans have experienced a relatively recent and rapid increase in average life expectancy, especially in countries with advanced economies, this increase is now slowing with further technological and medical advances yielding diminishing returns (4). With Jean-Marie Robine and coauthors’ calculation of the mathematical plausibility of a human living to the age of 122 years (2), it is not surprising that we have not seen any human exceed Jeanne Calment’s record set in 1997 when she died more than 20 years ago. Jay Olshansky and Bruce Carnes predict that a major breakthrough with the basic biology of aging might help increase life expectancy for some individuals, but we are unlikely to observe any appreciable increase in life span in the near future. One of the leaders in the study of compression of morbidity is Eileen Crimmins’ research group at the University of Southern California. By analyzing Health and Retirement Study data, Eileen Crimmins and coauthors reveal a decline in heart attack and stroke rates among people over the age of 70. Although this encouraging decline probably reflects both reductions in risk factors such as smoking and more effective medical interventions such as lipid therapy and better screening and treatment of high blood pressure (5), other counter trends are dampening the optimism. This progress, the authors point out, is undermined by increased rates of cancer, stroke, and diabetes among younger age groups. The future net impact: leveling off or even decline in average life expectancy. This potential harbinger of declines in health and longevity in the United States is echoed by Jay Olshansky’s work showing that obesity rates are on the rise and with them, so are rates of obesity-related diseases, the primary killers of adults—namely diabetes, cardiovascular disease, and cancer (6). As indicated by Keith Whitfield and colleagues, and by other studies, these problems are amplified among African Americans who on average have a 2-year lower life expectancy at age 65 compared with Caucasians (7,8). Notably, obesity, smoking, exercise, healthy diets, stress management, adequate sleep, and other potentially modifiable risk factors are primary influences of mortality. Thus, Victor Dzau’s and Jo Ann Jenkins’ call to arms to educate people about modifiable risk factors and to enable them to decrease their risks and increase their resilience comes with a critical urgency. Today’s boomers, in their 50s–70s, and members of generation X, in their 40s–50s, are at critical stages of their lives in determining their health spans. A societal embracing of a paradigm shift—the understanding that as the potential for longevity increases, so does the importance of health-related behaviors at all ages (including middle and older ages)—could extend health span and make aging an opportunity rather than an adversity. From Keith Whitfield and colleagues come a further call to arms, asserting that understanding health disparities requires more data from the oldest members of communities with otherwise lower life expectancies. They hypothesized that African Americans age 85 and older are a select cohort with shared attributes who have somehow overcome the various causes of decreased average life expectancy. One expect that these individuals have survival-related factors in common. However, these researchers report greater variability in older cohorts when compared with younger cohorts. This result suggest that although there are similarities among the oldest old, we still have much to learn about what allows some individuals to experience different rates of “biological aging” (9). In these pages, we also examine how we measure the biological process of aging and how these additional data could enable us to extend healthy longevity. Although the policy concerns of data collection from hundreds of thousands of people is a continuing discussion, we cannot deny that we are now in the age of “big data”. Today wearable devices can capture hundreds of data points about physical function. In the area of biology, a small sample of blood can now yield not only your entire genetic code, but also information about thousands of proteins, enzymes, metabolic markers and other indicators of both disease and health. Analysis of a small stool sample can quantify thousands of different bacteria populations (called the microbiome) which are increasingly being found to strongly influence both health and disease. Just as important, the fields of biostatistics and bioinformatics are catching up with this plethora of data, and new techniques will be able to integrate increasing amounts of data from different modalities. Monty Montano’s research group at Harvard provides insights into the power of data produced from a wearable device, an accelerometer that can capture a wide range of measures about physical activity while people conduct their everyday lives. Novel data such as the period of time a foot is not touching the ground while walking or the change over time in the span of a person’s gait show promise as markers of health or disease and may be especially sensitive to early changes in physical function. In the Pencina and colleagues study, gait speed was found to be a good proxy for both immune and muscle function at basic biological levels (10). In the future, the wide array of clinical and biological data being captured could be combined to potentially enhance the characterization of a person’s health status, to potentially discover a disease process or even to measure the biological rate of aging much earlier and more accurately than we can with current technology. Addressing the biological underpinnings of such work is a contribution by Annibale Puca’s laboratory, which concentrates on the biological characterization of the metabolic and immune systems and what features and mechanisms are associated with successful aging into the 10th and 11th decades of life. The authors describe how some long-lived individuals exhibit regulatory mechanisms that limit the impact of inflammation on mortality and vascular disease (11). As noted above in the article by Whitfield and colleagues, there is a great deal of heterogeneity in how people age. Understanding how these heterogeneous determinants of healthy longevity interact with one another and the environment elevates the importance of personalizing assessment and treatment. The article by Anastasia Gurinovich and colleagues identifies how the effects of specific genetic variants can differ by ethnicity as well as, likely, the geographic distribution of where that variant evolved (12). The apolipoprotein E gene can occur as one of the three common variants, and the E4 variant is a noted risk factor for both Alzheimer’s disease and vascular disease. Previous work has noted that the E4 variant or allele is, as one would predict, very uncommon in centenarians or people who live to 100 years or older. Other groups have found that another variant which is associated with living longer, E2, has increased frequency among centenarians. However, in the study by Anastasia Gurinovich and her colleagues, the effects of these variants can greatly vary according to ethnicity and geography. These and other gene-based differences according to ethnicity and geography may be an important mechanism by which nutrition and other local environmental exposures can have markedly different effects on a person’s health span and susceptibility to disease. John Earls and colleagues describe how clinical and laboratory data can be used to construct a measure of “biological age” (13). This methodology could leverage ongoing work by the National Institute on Aging and large health care systems, from Kaiser Permanente and Geisinger to the Veterans Administration which are archiving broad ranges of clinical and laboratory data from millions of patients and study participants. Future research could then test if combinations of data can enhance our ability to quantify the biological rate of aging and measure a person’s risk of common diseases much earlier than ever before. Large numbers of participants and patients may be required to account for the heterogeneity found worldwide in genetic, cultural, and environmental enablers of healthy longevity. Future research should seek to determine whether these measures of “biological age” can contribute to personalized wellness interventions and treatment plans that could enable health longevity. Jamison McCorrison and colleagues discuss the potential strategies to identify interventions that slow the biological rate of aging and suggest that more comprehensive data sets and studies are needed to translate genetic association data into clinical interventions (14). They propose that additional research is required to determine how specific longevity associated genes are activated and under what circumstances. Genetic and environmental associations will also require understanding cellular mechanisms and metabolic pathways that are reacting to specific stresses or optimal conditions. The authors then describe how additional data could inform us about potential therapeutic drugs and prevention strategies for aging-related diseases and hopefully healthy longevity. Current studies are underway, such as one from the National Institute on Aging’s Longevity Consortium, to gather clinical, biochemical, and biological data over time from both people with aging-related diseases and those who have prolonged health span such as centenarians and supercentenarians (those who live to 110 years old and older) like the 122 year-old Jeanne Calment. The National Academy of Medicine's Global Roadmap for Health Longevity provides a call to action to understand how individual biology, societal enablers, medical science, and technology could be harnessed to ensure that people worldwide can live longer, healthier, and more fulfilling lives. The potential for increased longevity elevates the importance of our health at all ages. Although historical reductions in childhood and adolescent mortality are key drivers of our longevity today, increasing health span in middle age and beyond is required if we seek to expand healthy longevity. Healthy longevity will require a new paradigm that increases research and resources that continue to support increased health span in midlife and older ages. It has long been noted that the “populations with high life expectancy enjoy low life disparity” (15). As the United States continues to experience persistent disparities in life expectancy by race (7), there is also now evidence that geographic disparities in life expectancy among U.S. counties are large and increasing (9). Additional advancements in addressing disparities by income, race, ethnicity, and geography are required if we are to reverse the recently observed reduction in U.S. life expectancy. As we are reminded in the editorial by Victor Dzau and Jo Ann Jenkins, many people across the world are depending on gerontologists to take action now. The call to action comes in response to the unprecedented and exciting opportunity that extended health spans and enhanced longevity present to us. Funding for this supplement was provided by AARP. The statements and opinions expressed herein by the authors are for information, debate, and discussion, and do not necessarily represent official policies of AARP. None reported.