Achieving healthy human longevity: A global grand challenge

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Science Translational Medicine  21 Oct 2020:
Vol. 12, Issue 566, eabd3816
DOI: 10.1126/scitranslmed.abd3816


With continued advances in science and technology, there is great potential to extend our healthspan as we age.

Victor J. Dzau

Elizabeth M. Finkelman

Celynne A. Balatbat

Eric M. Verdin

Roderic I. Pettigrew


Over the past century, major advances in medicine, public health, and socioeconomic development have led to unprecedented extensions of life expectancy worldwide. Coupled with declining mortality and fertility rates, a major demographic transition has emerged globally. In 2018, for the first time, the number of people over the age of 64 surpassed the number of children younger than 5. By 2050, nearly 20% of the world’s population will be over the age of 65.

Global population aging presents both new opportunities and challenges. The COVID-19 pandemic has challenged recent advances in science and medicine and underscored the vulnerability of older populations to emerging diseases, alongside existing age-associated susceptibilities to noncommunicable diseases. Without innovation and adaptation, societal aging is poised to strain health care systems, economies, and social structures worldwide. Health care costs will rise and public benefit programs will become strained or depleted. As families have become smaller and more disperse, limited support within the family may be available.

Yet, these and other looming stressors are not inevitable and could be mitigated, if not avoided, by accelerating biomedical and technological advancements, as well as socioeconomic infrastructures and policies to keep people healthier throughout their lives. By extending the health span, defined as the healthy years of life, societies can benefit from the tremendous social and economic opportunities that come with an active and vibrant older population.

Advances in aging science and technology

With continued advances in science and technology, there is great potential to improve the health and enrich the lives of older adults. By delaying the deleterious biological processes associated with aging, we could prevent debilitating illness and loss of function associated with aging.

Numerous studies have identified common cellular and molecular mechanisms underlying the aging process, demonstrating that biological aging is modifiable and in some organisms health span or life span can even be extended. Many of the genetic pathways underlying aging and age-related disease—such as the insulin/IGF-1 and mammalian target of rapamycin (mTOR) pathways—play a critical role in maintaining homeostasis in response to environmental modulators such as injury, infection, stress, or food availability. Scientists have also theorized that free radical molecules or reactive oxygen species, produced by mitochondria during fundamental metabolic processes, are a key mediator of the aging process. Other emerging areas of aging research include cellular senescence and senolytic therapy, regenerative medicine, immunoengineering, and genome editing and silencing. Therapies targeting these mechanisms and biological changes associated with aging are now being investigated in clinical trials (1). For example, senolytic compounds that selectively eliminate senescent cells are being studied in human clinical trials for osteoarthritis, glaucoma, and pulmonary fibrosis (2). Likewise, researchers are studying the effects of caloric restriction (3); metformin, a first-line drug for the treatment of type 2 diabetes (4); and rapamycin, an approved drug that inhibits mTOR, on the biology of human aging.

A fundamental question that remains is how interventions that show promise in improving life span or health span in model organisms will be evaluated in humans, where a complex interplay of factors underlies the aging process. Indeed, biological age often differs from chronological age. Some older individuals are less likely to develop age-related diseases than their age would predict, whereas some younger individuals prematurely develop age-related conditions. Thus, scientists have searched for biomarkers or other biological changes associated with aging and age-related declines that might act as “aging clocks.” Increasing evidence suggests that epigenetics plays an important role in the biology of aging. Other measures of biological aging have focused on telomere length and erosion. However, various proposed measures to quantify biological age may measure different aspects of the aging process, so a refinement of measures of human biological aging is needed (5). Further, even within an individual or organ there may be differential aging. Identifying validated biomarkers of aging in different tissues represents another key priority area for research.

Much like the pace of basic research, rapid advances in digital and engineering technologies demonstrate great promise for promoting healthy aging. Recent technological advances include telehealth and virtual care delivery methods, which have become increasingly utilized during the COVID-19 pandemic. Other technological advances include early molecular biomarkers for cancer that are digitally recorded and analyzed, remote monitoring devices to track glucose concentrations and blood pressure changes, and wearable biosensors to monitor indices of well-being, with online analytics and immediate feedback to guide action. Additionally, we are seeing rapid advances in brain-computer interface technology and exoskeletons developed to improve mobility and enhance recovery of motor function after injury or stroke. More broadly, digital technology can help to acquire widespread health-predictive data. Coupled with artificial intelligence, this could be used to track individual health trajectories over time and learn the importance of changes in monitored characteristics. For example, with in-home sensors, we can monitor the way people age and decipher actionable information about illness early in its course.

Evolving technologies that show immense promise include augmented reality, which may enhance lifelong learning and functional independence for older adults; electroceuticals and bioelectrics, such as nerve-stimulating electrical devices to treat epilepsy, migraine, and depression or to restore bladder control; regenerative medicine to repair diseased tissues and organs; and immunoengineering to modulate the immune system to prevent or treat illness. Recent digital technologies already allow the elderly to remain virtually connected to loved ones, helping to combat loneliness and social isolation.

Disruptive approaches to extend human health span

Despite recent progress, the current research and innovation ecosystem is not poised to deliver the transformative innovations needed to achieve healthy longevity. To achieve major breakthroughs, we need to reexamine our fundamental approach to aging research and innovation. The traditional biomedical research funding model continues to be largely risk averse. Typically, incremental and clearly feasible research is funded, whereas bold, high-risk but high-gain proposals are often less well supported. Similarly, we see a rather conservative approach to drug discovery, which is designed to target, manage, or cure one disease at a time. Further, aging research has been concentrated historically in areas such as the biology of model organisms, geriatric care, and Alzheimer’s disease. There is a need to expand the horizon of aging research and innovation by utilizing a convergence approach that includes biologists, geneticists, social and behavioral scientists, physical scientists, and engineers.

For these reasons, the National Academy of Medicine (NAM) has launched the Healthy Longevity Global Competition to catalyze breakthrough research and generate transformative and scalable innovations by mobilizing action across disciplines and sectors—from basic research to technology, care delivery, financing, community development, and social policy. An important goal of this Global Competition is to stimulate worldwide interest from scientists and innovators, thereby creating a global movement to dramatically increase innovation and groundbreaking advances in aging research (https://healthylongevitychallenge.org). In October 2019, NAM and global collaborators launched the Global Competition with the participation of 49 countries and territories. During the first phase of the competition over 3 years, more than 450 Catalyst Awards will be distributed globally, representing over US$30 million in seed funding to attract bold, audacious research ideas. In the second phase, “Accelerator Awards” will provide additional substantial funding or support for projects that have demonstrated proof of concept with potential for commercialization. In the third and final phase, one or more Grand Prizes totaling over US$4 million will reward breakthrough achievements with the promise of global impact.

Winners of the first cycle of the Catalyst Phase have just been announced, with funding spanning basic and biomedical science, clinical medicine, social science and public health, data science and artificial intelligence, and digital health. Funded projects include a smartwatch app for early Parkinson’s disease detection, sequencing of centenarian genomes, development of an implantable continuous hemodialysis device, gut microbiota optimization across the human life span, halting inflammaging through skin barrier restoration, nanocatalysis for improving health span, improving health span by natural killer cell activation, and development of a National Service Care Corps. Two additional funding cycles will follow in 2021 and 2022. The Catalyst Phase is distinguished from other funding initiatives in that it encourages participation and ideas from a diverse applicant pool and lowers some of the traditional barriers to entry for research and innovation. Notably, applications are evaluated primarily on the novelty of the ideas, rather than on preexisting data, demonstrated work, institutional capabilities, or feasibility alone. Further, subsequent phases of the competition are intentionally structured to encourage Catalyst Phase applicants and awardees to continue advancing their ideas to translation.

Real progress in achieving healthy longevity will necessitate transformative change across different sectors and policies. Indeed, achieving healthy human longevity requires a multipronged approach that includes accelerating biomedical and technological advancements to keep people healthier for the entirety of their lives; adopting socioeconomic infrastructures and policies that support health, well-being, and productivity into one’s senior years; optimizing systems providing health care, health promotion, and preventive services for aging populations; and implementing public policies to support healthy aging.

To help operationalize this approach, NAM has launched the Global Roadmap for Healthy Longevity, in parallel with the Global Competition. An international commission will assess the evidence and develop a comprehensive policy strategy for healthy aging. The resulting “Global Roadmap for Healthy Longevity” will provide an authoritative, evidence-based policy blueprint to guide effective solutions for healthy aging and longevity globally. The commission’s report, to be released in mid-2021, will be informed by three workstreams: (1) social, behavioral, and environmental enablers, (2) health care and public health systems, and (3) science and technology. Each workstream includes a two-day workshop of leading international experts, who will identify the most promising and scalable opportunities and priorities. The first workshop on social, behavioral, and environmental enablers took place in November 2019; the second on health care and public health systems took place in February 2020; and the third on science and technology is scheduled for early 2021. With equity at its center, particular consideration will be given to policy and practice, innovation, financing models, and monitoring metrics.


Global aging stands to fundamentally impact how families, communities, societies, industries, and economies function. As illustrated by the impact of the COVID-19 pandemic, innovative solutions are urgently needed to address the vulnerabilities of older populations to emerging pandemics and noncommunicable diseases and to maximize the number of years lived in good health.

Through the Global Roadmap for Healthy Longevity and the Healthy Longevity Global Competition, NAM seeks to lay the groundwork for a new global vision around healthy aging, catalyzing new medicines, treatments, technologies, and preventive and social strategies that could help to transform the way we age. Healthy longevity as the norm is within reach through contemporary societies collectively working to tackle this global grand challenge.


Competing interests: V.J.D. has served as a member of the board of Alnylam Pharmaceuticals and Medtronic Inc., where he received deferred compensation until 2018.

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