Precision Reprogramming-Restoring Function to Aged Cells.
Abstract
Sahu et al. (2024) demonstrate that targeted partial reprogramming with Oct4, Sox2, and Klf4 (OSK) delivered via adeno-associated virus (AAV) to Cdkn2a-positive cells rejuvenates senescent cells while maintaining cellular identity. In a progeroid and naturally aged mouse model, a single AAV injection improved lifespan, reduced inflammation, restored tissue integrity, and enhanced wound healing. Complementary results in human fibroblasts confirmed Cdkn2a-driven OSK expression attenuated inflammation-associated genes during replicative senescence and treatments inducing DNA damage. These encouraging results highlight its potential as a safer alternative to systemic senolytic therapies for age-associated disorders.
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Research summary
Targeted partial reprogramming with OSK rejuvenates senescent cells and improves lifespan in aged models. This research addresses the root causes of aging by demonstrating a method to restore function in aged cells, which is directly relevant to longevity and age-related disorders.
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