Gene Therapy-Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice.
Level 5 - mechanism / opinion, no new human data
Animal (mouse) and in vitro (human cell) preclinical study
PubMed 38381405 · doi:10.1089/cell.2023.0072
What was done
Researchers systemically delivered adeno-associated viruses (AAV) encoding an inducible three-factor partial reprogramming system (OCT4, SOX2, and KLF4; OSK) to 124-week-old male wild-type mice to assess impacts on remaining lifespan and frailty. They also expressed exogenous OSK in cultured human keratinocytes to evaluate changes in epigenetic aging markers.
What was found
Inducible OSK gene therapy extended the median remaining lifespan of 124-week-old male mice by 109% relative to wild-type controls. It also yielded a statistically significant improvement in mouse frailty scores and other health parameters. In human keratinocytes, OSK expression induced significant changes in epigenetic markers indicative of age reversal. Specific group sizes, survival curves, and numerical scores for frailty and epigenetic markers were not reported in the abstract.
Why it matters
This provides proof-of-concept in an animal model that partial cellular reprogramming initiated extremely late in life can simultaneously improve physiological health parameters and extend remaining lifespan.
Limits
The abstract reports on male mice only, preventing generalization across sexes. Sample sizes, exact dosage protocols, hazard ratios, and detailed quantitative outcomes for frailty and epigenetic assays are not provided in the abstract. Animal and cell-culture findings cannot be directly applied to human clinical longevity or safety.