The big sea change of the past 10 to 15 years in aging research is that the scientific community is now near entirely behind the idea that aging is a viable target for therapy, and that we should be working towards greater healthy human longevity. Prior to this time, aging was near entirely a “look but don’t touch” field, in which any talk of medical intervention in aging was strongly discouraged.
Making this change come about was a battle of years of patient advocacy (such as by the SENS Research Foundation and Methuselah Foundation), argument, and incremental advances in the science funded by small sums of hard-to-find research funding. It is perhaps hard for people today to recall how opposed the culture was to the idea of extending healthy life spans.
The present challenge is different: to ensure that the now willing workers and funding institutions direct their attention towards projects that will make a meaningful difference. Near all present work on intervention in the aging process is intended to do no more than modestly slow aging, tinkering with metabolism to slightly slow the accumulation of cell and tissue damage, or slightly blunt the consequences of damage. But the research community can do far better than this; it is possible to repair the damage that causes aging in order to produce rejuvenation. That strategy should be the primary focus on the research and development community, and it is not.
The initiative mentioned here, the Health Longevity Global Competition, is an example of this problem. If one digs in to see what exactly it is that they are supporting, one sees that it near all consists of projects that will clearly make no meaningful difference to the healthy human life span. It is not enough to have the enthusiasm and support of the research community. The strategy must also be correct.
Achieving healthy human longevity: A global grand challenge
Over the past century, major advances in medicine, public health, and socioeconomic development have led to unprecedented extensions of life expectancy worldwide. 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.
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. 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.
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.”
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.
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. 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.
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