Charles Brenner called the language of 'aging reversal' the language of fabulists and proposed testing anti-aging drugs on chemotherapy survivors, while Kamil Pabis, an opponent from the same anti-hype camp, replied that the entire dispute is simply about words
Charles Brenner called the language of 'aging reversal' the language of fabulists and proposed testing anti-aging drugs on chemotherapy survivors, while Kamil Pabis, an opponent from the same anti-hype camp, replied that the entire dispute is simply about words
Between September 24 and 27, a debate among three specialists about geroscience unfolded on X. Kristin Glorioso, a physician and founder of a longevity company, asked biochemist Charles Brenner how one could even verify in humans that a drug reverses aging. Brenner replied that the goal is unattainable and proposed instead a measurable improvement in the aging trajectory, with a concrete experimental design. Aging researcher Kamil Pabis objected that the entire conflict comes down to terminology.
On September 24, Glorioso wrote to Brenner: a trial spanning an entire lifespan cannot be run, so surrogate markers of aging that are detectable within a researcher's lifetime are needed. Otherwise, how can one prove that a drug reverses aging?
Brenner replied two days later:
To start, let us set achievable goals. […] Aging reversal has not been achieved even in worms, flies, and mice, and it is not a reasonable goal. Cancer survivors treated with broad classes of drugs age faster; they could become an ideal population for finding and testing drugs that improve the trajectory.
In worms, flies, and mice (short-lived model organisms) aging reversal has not been accomplished, which means, in Brenner's view, it is a pointless goal for translational geroscience (the effort to move laboratory findings into the clinic). He proposes instead a measurable improvement in the aging trajectory and names a specific model group: in breast cancer survivors, epigenetic age (an estimate of biological age based on DNA methylation marks) runs one to two years higher than in peers who did not undergo chemotherapy, and in colorectal cancer patients it rises over the course of treatment. In this group the effect of a new drug would become apparent faster than in healthy individuals. Epigenetic age is suitable for such a test: reviewing consumer biological-age tests, Brenner had already drawn the same line. As a personal health verdict for a single person, these aging markers are too noisy, but they remain a workable tool for rapid drug testing across groups of people.
That same day, replying to a pharmaceutical industry investor, Brenner sharpened the point:
Translational geroscience will be doomed if it adopts the aging-reversal language of known fabulists.
By "fabulists" he means those who pass off a compelling narrative as a proven result, and he supports the claim by linking to his peer-reviewed 2022 paper in Archives of Gerontology and Geriatrics, a critique of the best-selling book on aging. Brenner heads the Department of Metabolism at the City of Hope cancer center.
On September 27, aging researcher Kamil Pabis of VitaDAO, a community that funds aging research through blockchain, entered the debate. He objected to Brenner:
This is semantics. One can readily reverse a broad set of functional changes characteristic of aging without "reversing aging" per se. That is a perfectly feasible trial design, and by statistical power it outperforms a trajectory study.
Brenner responded with a single line ("yeah, that will be easy") and offered no argument.
The dispute ended without answering its central question: what should a clinical trial demonstrate for it to count as a victory over aging, an improved trajectory or reversed functional changes?