The partial reprogramming of mice by gene therapy extends their life span and reverses age-related changes.
The process of aging is complex and can be described as a chronic dysregulation in cellular processes that leads to the deterioration of tissue and organ functions. Although aging is not currently preventable, the impact it has on longevity and healthspan can be reduced by interventions that return these cellular functions to optimal function. Recent studies have shown that partial reprogramming with the Yamanaka factor (or subset, OCT4, SOX2, KLF4 and OSK) reverses age-related changes both in vitro as well as in vivo. It is not known if the Yamanaka factor (or subsets) can extend the lifespan of wild-type mice. We show here that AAVs encoding the inducible OSK systems, systemically delivered to 124-week old mice, extends their median remaining life by 109% compared to wild-type controls, and improves several health parameters. We also observed that frailty scores improved significantly, indicating we had been able to increase lifespan and improve health. In addition, we found significant epigenetic markers for age-reversal in human keratinocytes that expressed exogenous OSK. This suggests a possible reregulation genetic networks into a younger and potentially healthier state. These results could have significant implications for the development and testing of partial reprogramming to reverse age-associated disease in elderly people.
All authors worked at Rejuvenate Inc. Rejuvenate Bio, a therapeutics firm that develops gene therapies for age-related diseases.
Source:
https://www.biorxiv.org/content/10.1101/2023.01.04.522507v1
