New paper first to show that gene therapy-mediated partial reprogramming extends lifespan and reverses age-related changes in aged wild mice.
Longevity biotech Rejuvenate Bio has made new progress towards showing that gene therapy-mediated partial reprogramming can potentially combat age-related diseases and extend lifespan. The San Diego-based company company claims that its paper, published this week in the journal Cellular Reprogramming, is the first to demonstrate that epigenetic reprogramming can extend overall lifespan in normal, aged mice, rather than the genetically modified mice used in other studies.
Cellular reprogramming using transcription factors has emerged as a key strategy for the rejuvenation of aging cells – erasing markers of cell damage and restoring epigenetic markers. These transcription factors, also known as Yamanaka factors, can be used to convert cells into pluripotent stem cells which can divide into any cell type of the body. Rejuvenate Bio’s approach involves partial reprogramming using some of the Yamanaka factors, known as OSK (Oct4, Sox2, Klf4), to reverse age-related changes.
In the study, adeno-associated viruses encoding the reprogramming factors were systemically delivered to 124-week-old male “wild-type” mice (equivalent to approximately 77 human years). The results showed a 109% increase in median remaining lifespan compared with wild-type controls, accompanied by improvements in various health parameters. Notably, frailty scores indicated significant enhancements, suggesting an improved healthspan in the treated mice.
“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 Dr Noah Davidsohn, CSO at 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.”
Furthermore, the study reported significant age-reversal in heart and liver tissues, as well as human keratinocytes, demonstrated by DNA methylation clocks. To understand the impact of OSK overexpression on human cells, the researchers introduced OSK into HEK001 keratinocytes obtained from a 65-year-old male patient’s scalp. The treated keratinocytes exhibited significant epigenetic age reversal compared with untreated or GFP-transduced cells.
“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,” said Dr Dan Oliver, CEO of Rejuvenate Bio. “These results may have important implications for the development of partial reprogramming interventions to reverse age-associated diseases in the elderly population.”
As the technology being developed by Rejuvenate Bio directly reverses a cell’s age, Davidsohn told us that the company is now focusing its development on “neurological and muscular diseases that are heavily influenced by a patient’s age.”
“Specifically, diseases that have been tough to treat with traditional medicine or gene therapy approaches due to either a lack of understanding or complex genetic background,” he added.
Founded on scientific research from the Wyss Institute at Harvard Medical School, Rejuvenate Bio is developing a gene therapy pipeline with potential in treating chronic age-related diseases in both humans and animals. This latest news comes on the heels of the company’s recent announcement of a strategic partnership to advance the development and commercialization of its gene therapy designed to address canine osteoarthritis.
