FDA to Include Aging in Its Regulatory Science Priorities
FDA to Include Aging in Its Regulatory Science Priorities
On October 1, at ARDD, a conference on the science of aging and drug development, FDA staff discussed how to design trials for therapies that target the mechanisms of aging. The agency's updated regulatory science priorities document will include this topic for the first time; Justin Pencenstadler was introduced on the panel as the official responsible for designing such trials.
The session was moderated by Andrew Brack of ARPA-H, the American agency that funds high-risk biomedical programs. Jeffrey Siegel, director of FDA's Office of Scientific Drug Evaluation, outlined two paths. In one, a drug sequentially demonstrates efficacy against several age-related diseases, and the combined results build a case for a shared underlying mechanism. In the other, a trial enrolls people whose age-related decline simultaneously affects memory, physical strength, hearing, and vision, and seeks a composite measure that captures the full picture.
Steven Kozlowski, FDA's chief scientist, proposed treating aging as a common risk factor for many chronic diseases. He compared the idea to the g-factor of intelligence in psychology: a single quantity that helps explain performance across different cognitive tasks. Trials would need a similar measurable indicator of organismal state, one that links different age-related changes to each other. Pencenstadler suggested starting with unambiguous outcomes, mortality and incidence of age-related diseases, in people with notable decline, and then transitioning to faster surrogate endpoints.
This sequence protects the trial design from a familiar trap. SGLT2 inhibitors for type 2 diabetes and GLP-1 agonists such as semaglutide reduce cardiovascular mortality through a well-characterized pathway. In a longevity trial, any survival benefit could simply reflect that established action rather than a broader effect on aging. The panel therefore proposed strict participant selection and measurement of outcomes beyond the drug's proven therapeutic range, such as hearing or mobility.
The shift is visible in the agency's own language. The 2022 FDA regulatory science priorities document listed pandemic preparedness, data, and consumer choice; aging did not appear. A comparable regulatory acknowledgment has happened before: in 2015, the FDA agreed to accept delay of multiple age-related diseases as a single composite endpoint for the metformin TAME trial, which over the following decade never enrolled a single patient, because a cheap generic without patent protection gave no pharmaceutical company an incentive to fund it. Even with money, the trial needs one more element: a biomarker, a measurable indicator of aging itself rather than of the individual diseases it causes. Steve Horvath, the creator of epigenetic aging clocks, made exactly this point from the ARDD stage:
Suppose aging is recognized as a disease. How do we define it? [...] We cannot get there without molecular biomarkers of aging.
Pencenstadler asked the field to form a consortium in which competing companies, before any product reaches market, jointly agree on shared biomarkers and regularly bring data to the regulator. Lowell Zeta, acting chief of staff to the FDA commissioner, continues this call. As early as September, on an H-SPAN panel on regulatory strategies for longevity biotechnology, he urged industry to submit biomarkers for qualification and to use Operation Trailblazer, a channel for early human trials. Now he framed it as a test for the agency itself:
This is a test for the future FDA: whether the agency can adapt to rapidly evolving science in this field.