Turning Back the Clock

Imagine if we could turn back the clock on age-related illnesses by reprogramming our cells to be younger? Reversing the aging process of cells may seem like science fiction, but it is an active field of scientific exploration called regenerative medicine.

In a recent Nature Aging paper, Genentech and Salk Institute scientists show that cellular reprogramming techniques safely delayed or reversed some of the biological and physiological consequences of aging in mice. This discovery helps bring us closer to preventing or reversing age-related diseases in humans. The study was led by Genentech’s Henri Jasper and Kristen Browder, Salk’s Juan Carlos Izpisua Belmonte, and their teams.

The inspiration for this research began in 2007, when Dr. Shinya Yamanaka and team showed that turning on four genes that are silenced in mature cells could turn them back into pluripotent stem cells – immature cells that have the potential to become any type of cell. Since this Nobel Prize-winning discovery, scientists have explored if they can use this approach to maintain or restore the healthy function of certain tissues in the body.

It turns out they could – at least in animals. Using mice that are genetically prone to age rapidly, scientists out of the Salk Institute reprogrammed cells to become more youthful by introducing Yamanaka’s four genes, which erased genetic marks of stress that caused aging in these cells. The treated mice showed fewer signs of rapid aging and had longer lifespans than untreated mice.

In the most recent publication, Genentech and Salk scientists worked together to test the long-term safety of this approach in healthy mice. They found that partially reprogramming cells - by turning Yamanaka’s four genes on and off in cycles - over an extended period of time had no observable negative effects on the health of the mice. In this study, the results also confirmed that partially reprogramming cells reduced age-related changes in healthy mice, not just mice that age rapidly. In many ways, noted in this study, the treated mice resembled younger animals. For example, skin wounds healed better than in untreated mice.

Interestingly, the researchers found that youthful characteristics of the mice became more pronounced the longer treatment lasted. This suggests that partial reprogramming can reverse some processes of aging in mice, but additional studies are needed to confirm whether this technique could actually delay noticeable effects of aging in mice.

Our scientists are now exploring whether partial reprogramming can be used to tackle age-related disease. For example, they are investigating new ways of delivering the treatment to specific tissues like the lung.

Around the world, people are living longer, and chronic illness and diseases of aging are more prevalent. Regenerative medicine is an exciting field because treatments that prevent or reverse age-related diseases could have an incalculable impact on global health. While potential treatments remain years away, this research provides critical new insights into our understanding of the basic biology behind cellular reprogramming.