Aging biologist Pyotr Lidsky argues a genetic program drives aging, not damage accumulation, and faces two counterexamples in an X thread: cancer and a retinal rejuvenation mechanism that works by clearing oxidative damage

Aging biologist Pyotr Lidsky argues a genetic program drives aging, not damage accumulation, and faces two counterexamples in an X thread: cancer and a retinal rejuvenation mechanism that works by clearing oxidative damage

On September 27, aging biologist Pyotr Lidsky posted on X: no other disease is considered to be caused by damage, so aging should be no exception. Two researchers pushed back: evolutionary biologist Alexander Wolf with the example of cancer, and Mike Lee with a 2025 paper on an enzyme that rejuvenates the retina by clearing oxidative damage.

“Is aging caused by damage or by a genetic program? I believe in the program and reject damage as the primary cause,” Lidsky wrote. “Is damage the primary cause of any other disease? I don’t know of one (a broken leg doesn’t count).”

Wolf is the author of a theory of aging through tumor suppression: suppressing cancer comes at the cost of tissue deterioration from accumulated DNA mutations. “Yes, cancer is caused by somatic mutations, and that is damage,” he wrote.

Lidsky drew the line between genes and noise. “These are specific changes in specific genes, not a vague cloud of molecular noise, entropy, and other poorly defined things,” he wrote. “By your logic, apoptosis is also caused by damage, because caspases destroy proteins.” Apoptosis is the programmed death of a cell for tissue renewal; no one considers it damage. Lidsky had already described one such program in August with Mikołaj Ogrodnik: the pathogen control hypothesis, which proposes that waning immunity in aging individuals may have been selected for to keep them from infecting relatives.

Mike Lee countered Lidsky with a 2025 paper on retinal pigment epithelium cells, which nourish the light-sensitive cells of the eye. The OSK method (partial reprogramming of a cell using three genes) had already restored vision in aged mice by resetting the epigenetic age of neurons, their molecular clocks of aging. The new study found that in the retina, OSK also activates the enzyme GSTA4, which degrades 4-HNE, a toxic product of lipid oxidation that accumulates with age. Overexpression of GSTA4 alone was “sufficient and necessary”: it halved the biological age of retinal cells and restored their vision without resetting the epigenetic program. “The cause of aging is the accumulation of oxidative damage; everything else is secondary,” Lee wrote.

This finding also undercuts OSK as evidence for the epigenetic nature of aging. Lidsky replied briefly: “This is a specific molecular mechanism. And the consensus is that oxidative damage is not the cause of aging.” This was a reference to the free radical theory of aging, which dominated the field for decades but was never confirmed as a cause of organismal aging.

Lidsky applied the same criterion to dismiss Lee’s argument: the dispute over the boundaries of the word “damage” remains unresolved. Lidsky and Wolf debated for close to a day, testing their theories against new cases: why non-dividing tissues such as the brain age, and why single-gene mutations and obesity accelerate aging. On worms, Wolf answered plainly: he does not know. On mutations and obesity, Lidsky pointed solely to inflammation; Wolf countered: “We do not know of a single accelerated aging syndrome caused by inflammation,” and Lidsky has not yet replied.