Fight Aging!

A great deal has changed in these last few decades in the field of aging research. From the 60s onward to the 90s, aging research was increasingly characterized by a philosophy of "look but don't touch", an effort to distance academia from the growing anti-aging industry and its hype. It made itself a backwater science in which talk of intervention was aggressively discouraged by leaders in the field. Starting in the 90s, with studies showing significant life extension in lower animals following single gene mutations, it became impossible to ignore the potential to treat aging as a medical condition in humans.

Nonetheless, change comes only slowly in the scientific community. It was still a battle following the turn of the century to dismantle the old scientific culture and replace it with one in which researchers and funding institutions were enthusiastic about intervention in aging. That required a great deal of advocacy and philanthropic funding, accompanied by incremental advances in the science, a matter of bootstrapping progress. Ultimately it worked, of course, and now the research community is openly focused on producing therapies to slow and reverse aging, targeting the underlying mechanisms of aging. An industry has arisen, applying a great deal more funding to the challenge than is available to academia, and a wave of clinical trials will take place over the next five years.

Aging research: A field grows up

When I joined the longevity field, there had already been a shift from simply observing animals as they age to instead identifying regulators that could greatly alter lifespan, thanks to pioneering invertebrate genetic studies in the 1990s and early 2000s that discovered most well-conserved longevity pathways, particularly caloric restriction and the insulin/IGF-1 and TOR signaling pathways. What has changed in the past two decades? There have been at least three major shifts the aging/longevity research that will shape the field in the years to come.

The first shift is in the perspective of regulation: the concept that aging is indeed regulated, and not simply the result of accumulated damage. Once the regulators of longevity were found, there was still a general notion that these pathways primarily determine levels of cell autonomous damage repair. As molecular regulators of longevity and their networks have been identified, it has become clear that non-cell autonomous signaling coordinates rates of aging and response to damage across cells and tissues. In the future, the acknowledgment that these signals are integrated and can affect the body systemically will shape the types of therapeutics we develop, focusing on whole-body versus tissue-specific approaches, depending on the problem being solved.

A second large shift is in the aims of the field, from lifespan to healthspan. While maximum lifespan is still often the focus of the popular press, there is growing recognition that treating aging and age-related diseases are not mutually exclusive goals. Therefore, better understanding of how metabolic disorders, frailty, cardiovascular diseases, cognitive decline, reproductive aging, and other age-related changes are regulated might not only yield treatments for those disorders, but might ultimately increase lifespan as well. Maintaining functions with age may not only have a great impact on quality of life, but also may help us find treatments that generally slow aging.

A third shift is the translational focus of the longevity field, from an almost entirely academic endeavor to one that is being taken up by industry and clinics - that is, the findings we have made in academic labs are on the verge of becoming actual aging treatments. In the most immediate future, large-scale clinical trials of some of the best-studied longevity drugs (e.g., rapamycin and metformin) and testing of dietary interventions and mimetics may lead to aging treatments. New biotech companies have sprung up with a wide range of goals, from repurposing already-approved drugs for new aging treatments and exploring how the pathways we have discovered over the past 20 years might be harnessed to treat aging, to high-throughput and AI-driven approaches to search for new candidate aging drugs. Circulating blood factors first identified in parabiosis experiments, drugs that target senescent cells, and cell reprogramming and regeneration approaches have moved from concepts to testing, while molecular clocks are beginning to be used as diagnostics.

Luckily, we have finally matured beyond asking whether it is right to study aging, as it is being increasingly recognized that efforts to slow aging will be broadly beneficial; in fact, some of those approaches will help those with other disorders (e.g., muscle diseases, menopause and mid-life issues, and neurodegenerative diseases). Instead, we can ask, which of the multiple approaches being tested now will have the greatest impacts on our lives in the foreseeable future, and how can we all benefit?