Information Theory of Aging (Sinclair)

What it proposes

Aging is fundamentally the loss of cellular information — specifically epigenetic information that tells each cell its identity and operational state. The DNA sequence (the “hardware”) is largely preserved; the epigenome (the “software”) drifts.

The key claim is that this lost information can in principle be recovered, because a backup copy is somehow accessible to the cell. The empirical basis is partial Yamanaka reprogramming: brief expression of OSK (Oct4, Sox2, Klf4) can reset the epigenome of aged cells without loss of identity.

Key supporting work

• Lu et al. 2020 — AAV-delivered OSK restored vision in a glaucoma mouse model and a normally-aged optic nerve model.
• Multiple subsequent in-vivo partial-reprogramming studies in mice in kidney, muscle, brain, retina.
• DNA-methylation clocks reset during reprogramming, supporting the “clocks measure something causal” interpretation.

Critiques

• “Information” in this framing isn’t formally defined.
• Brief reprogramming does change epigenome, but the causal claim that this reverses functional aging in mammals is still being established.
• Risk of inducing pluripotency and tumour formation has plagued the in-vivo reprogramming field; safety in long-lived mammals is unknown.
• Some prominent rejuvenation results from this framework have been partially walked back or remain controversial.

Why it’s influential

The information-theory frame underwrites much of the partial-reprogramming industry now in development (Altos Labs, NewLimit, Retro Biosciences, Turn.bio).

Related entries

Epigenetic alterations, Epigenetic clocks, Partial reprogramming, David Sinclair.