CAMBRIDGE, MA — Scientists at Harvard Medical School and the Sinclair Laboratory have demonstrated a reversal of biological ageing in multiple mouse organs of up to 57%, using an expanded gene therapy protocol that reprogrammes cells by resetting their epigenetic clocks — the molecular markers that track and regulate how cells age.
The research, published in the journal Cell, builds on earlier work by Professor David Sinclair that demonstrated partial epigenetic reprogramming in mouse retinal cells. The new study extends the approach to kidneys, cardiac muscle, and skeletal muscle simultaneously, using a cocktail of three Yamanaka factors delivered via an adeno-associated virus vector with a precision timing system that prevents cells from reverting to a stem-cell state.
The Results
Aged mice treated with the gene therapy showed kidney function improvements of 41–57% as measured by glomerular filtration rate, restored retinal response to light comparable to animals half their chronological age, and cardiac muscle cell gene expression patterns indistinguishable from young adult mice after twelve weeks of treatment.
Crucially, none of the treated animals developed tumours — a risk associated with earlier reprogramming approaches that caused cells to become cancerous — over an 18-month observation period.
"This is still mice," cautioned co-author Dr Emma Yu. "The gap between mice and humans in biology is wide. But we now have a clear proof-of-concept that multi-organ epigenetic rejuvenation is possible without catastrophic side effects, and that is the foundation we needed to move forward."