Rejuvenate Bio Announces Gene Therapy-Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in the Journal Cellular Reprogramming

Aging is a complex process characterized by cellular dysregulation leading to deteriorated tissue and organ function. While aging cannot be prevented, interventions targeting cellular processes offer potential for mitigating its impact on health and lifespan in the elderly. Rejuvenate Bio’s research focuses on partial reprogramming using the Yamanaka factors, specifically OCT4, SOX2, and KLF4 (OSK), to reverse age-related changes.

In this study, systemically delivered adeno-associated viruses (AAVs) encoding an inducible OSK system were administered to 124-week-old male mice, equivalent to approximately 77 human years. The results demonstrated a remarkable 109% increase in median remaining lifespan compared to wild-type controls, along with improvements in various health parameters. Notably, frailty scores showed significant enhancements, indicating improved healthspan in treated mice. The active group also reported significant age-reversal in heart and liver tissues, as well as human keratinocytes, as indicated by DNA methylation clocks.

To understand how OSK overexpression impacts human cells, OSK was also introduced into HEK001 keratinocytes obtained from a 65-year-old male patient’s scalp. The researchers observed significant epigenetic age reversal in the treated keratinocytes compared to untreated or GFP-transduced cells. These findings, along with the data from mice, indicate that AAV-mediated gene therapy delivering OSK extends lifespan in mice while enhancing health parameters and reverses aging biomarkers in both mouse and human cells.

“For the first time, we extend median remaining lifespan in extremely old wild-type mice, accompanied by improved health outcomes via systemic AAV-based partial reprogramming therapy,” said Noah Davidsohn, Ph.D., Chief Scientific Officer, Rejuvenate Bio. “Our study demonstrates profound age reversal in wild-type mice through exogenous OSK expression, evidenced by restoration of genomic methylation patterns characteristic of younger cells—a validated hallmark of age reversal. Our approach could potentially address the growing burden of age-related diseases in human populations, and we look forward to translating our findings into potential therapeutic interventions for aging-related conditions.”

“This is the first published work to actually have epigenetic reprogramming extend overall lifespan in normal mice,” said Dan Oliver, Ph.D., CEO, Rejuvenate Bio. “The study’s analysis of human keratinocytes expressing exogenous OSK also revealed significant epigenetic markers of age reversal, suggesting a potential restoration of genetic networks to a younger, healthier state. These results may have important implications for the development of partial reprogramming interventions to reverse age-associated diseases in the elderly population.”

About Rejuvenate Bio

Rejuvenate Bio is a biotechnology company dedicated to developing novel gene therapies for chronic age-related diseases. Rejuvenate Bio has built a gene therapy pipeline with huge potential in chronic disease by utilizing clinically validated gene targets and a delivery approach that ensures well tolerated, durable expression. Founded on scientific research developed at the Wyss Institute at Harvard Medical School, Rejuvenate Bio has developed groundbreaking therapies to treat chronic age-related disease in both humans and animals. The company is headquartered in San Diego, CA. For more information, visit www.rejuvenatebio.com.

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