In a groundbreaking study, US researchers have unlocked a new frontier in the fight against ageing and age-related diseases. The study, conducted by a team of scientists at Harvard Medical School and Massachusetts Institute of Technology (MIT), has published the first chemical approach to reprogramme cells to a younger state.
Previously, this was only achievable using a powerful gene therapy. The findings, published in the journal Aging-US, builds upon the discovery that the expression of specific genes, called Yamanaka factors, could convert adult cells into induced pluripotent stem cells (iPSCs).
The discovery, which won the Nobel Prize in 2012, raised the question of whether it might be possible to reverse cellular ageing without causing cells to become too young and turn cancerous.
In the new study, the researchers screened for molecules that could, in combination, reverse cellular ageing and rejuvenate human cells.
They developed high-throughput cell-based assays to distinguish young cells from old and senescent cells, including transcription-based ageing clocks and a real-time nucleocytoplasmic protein compartmentalisation (NCC) assay.
In the exciting discovery, the team identified six chemical cocktails that restore NCC and genome-wide transcript profiles to youthful states and reverse transcriptomic age in less than a week.
“Until recently, the best we could do was slow ageing. New discoveries suggest we can now reverse it,” said lead scientist David A. Sinclair, Professor in the Department of Genetics at Harvard.
“This process has previously required gene therapy, limiting its widespread use,” he added.
The Harvard researchers previously demonstrated that it is indeed possible to reverse cellular ageing without uncontrolled cell growth by virally-introducing specific Yamanaka genes into cells.
Studies on the optic nerve, brain tissue, kidney, and muscle have shown promising results, with improved vision and extended lifespan observed in mice and, recently, a report of improved vision in monkeys.
The implications of this new discovery are far-reaching, opening avenues for regenerative medicine and, potentially, whole-body rejuvenation. By developing a chemical alternative to age reversal via gene therapy, this research could revolutionise the treatment of ageing, injuries and age-related diseases and offers the potential for lower costs and shorter timelines in development.
On the heels of positive results in reversing blindness in monkeys in April 2023, preparations for human clinical trials of the lab’s age reversal gene therapy are in progress.
The team at Harvard envisions a future where age-related diseases can be effectively treated, injuries can be repaired more efficiently, and the dream of whole-body rejuvenation becomes a reality.
“This new discovery offers the potential to reverse ageing with a single pill, with applications ranging from improving eyesight to effectively treating numerous age-related diseases,” Sinclair said.