Researchers from the American company Rejuvenate Bio have just pre-published a study in which they claim to have extended the life expectancy of elderly mice and reversed age-related changes thanks to gene therapy that consists of introducing 3 genes of the known as Yamanaka or OSK factors, particularly active in embryonic cells. The results, which have not yet been reviewed by other experts (certified by a peer review) could demonstrate that this type of therapeutic interventions will benefit the increasingly aging population around the world.
Aging is a complex process best characterized as the chronic dysregulation of cellular processes leading to impaired function of tissues and organs. While aging cannot currently be prevented, its impact on lifespan and health in the elderly can potentially be minimized through interventions that aim to return these cellular processes to optimal functioning.
It was administered systemically in 124-week-old mice (the equivalent of 77 human years), managing to double life expectancy, by increasing 7% in absolute value. In addition, they observed a significant improvement in fragility scores, indicating that lifespan could be improved and increased. Furthermore, in human keratinocytes expressing exogenous OSK, they observed significant epigenetic markers of age reversal, suggesting potential re-regulation of gene networks to a younger and potentially healthier state.
Aging is associated with increased susceptibility to adverse health outcomes that clinicians can capture using a frailty index (FI), where people are scored based on a subset of age-related health deficits. High composite scores reflect a frail state and increased susceptibility to poor health outcomes.
A similar index in mice can be used to assess aging and the effects of aging interventions. The researchers observed a significant reduction in IF from 7.5 points for the doxycycline-treated control mice to 6 points for the TRE-OSK mice, suggesting that increased lifespan was correlated with better overall health of those mice.
A discovery that will not have immediate effect
Taken together, the mouse and keratinocyte data suggest that AAV-mediated gene therapy delivered by OSK increases lifespan in mice with improved health parameters and reverses biomarkers of aging in human cells. “The result is very striking and seems to endorse the rejuvenating potential of this strategy. Despite this, the real application of this discovery is very distant and should only be taken as one more step in research in this line”, Manuel Collado, director of the Laboratory of Cellular Senescence, Cancer and Aging at the Institute of Sanitary Research of Santiago de Compostela (IDIS).
In his opinion, “it must also be taken into account that the work was carried out by a biotechnology company with obvious financial interests in this area of research and we know that this frequently conditions the validity of the results. In this case, moreover, given the enormous competition that has thrown several companies into the race that pursue this same promise of rejuvenation. It seems that the speed of trying to show themselves as the first to achieve it has not allowed for sufficiently thorough experimentation and analysis”.