What would it take to reverse biological age? A brief review of current candidates

Partial reprogramming (Yamanaka-factor based)

This is the most direct "reset" concept: push cells toward a younger gene-control state without wiping their identity.

A key public result in mammals

In very old male mice (124 weeks), a systemic AAV gene therapy delivering an inducible OSK program (a subset of Yamanaka factors) reported ~109% median remaining lifespan extension and better frailty scores versus controls (Macip et al., 2024).

A key public result linked to Altos-affiliated science

A 2025 Cell paper describes a broad aging/disease pattern the authors call "mesenchymal drift" across many tissues, and reports it is reversed by partial reprogramming in their models (Lu et al., 2025).

Where humans are right now

As of January 28, 2026, Life Biosciences announced FDA IND clearance to begin a Phase 1 study of ER-100 (AAV2-OSK) for optic neuropathies (eye/optic nerve). That is local (eye) and focused on safety first (Life Biosciences, 2026).

The "reset" idea is moving forward, but the human work is still narrow, and whole-body delivery is a very different (harder) problem than "in the eye."

Why this is still far from "end aging"

To "end aging" whole-body, you likely need all of the following to be true at once:

• Safe control (dose, timing, shut-off) in many tissues
• No big rise in cancer risk over decades
• Delivery that works in the whole body (and can be repeated)
• Durable functional gains (not just "younger markers")
• Strong safety in real humans (diverse genetics, comorbidities)

None of that is solved yet in public human data.

Other approaches that might contribute (but won't "end aging" alone)

Senolytics (clearing senescent "zombie" cells)

A U.S. NIA summary of a clinical trial in older women reported only subtle/limited benefits for bone health versus control, despite strong mouse results (NIA, 2025). There are also early human feasibility/safety studies (e.g., D+Q in older adults), but they are not the same as proving big lifespan effects (Millar et al., 2025).

mTOR inhibitors (rapamycin / rapalogs)

Reviews note promising animal data and some early human signals (often immune-related endpoints), but no human trial has shown lifespan extension, and safety/tolerability tradeoffs matter (Roark et al., 2025).

Metformin

Metformin is widely discussed as a candidate "gerotherapeutic," but the human evidence for anti-aging effects is still debated, and definitive trial results for aging outcomes are not in hand (Keys et al., 2025).