Prominent among these is the genetic intervention first shown to turn adult somatic cells into embryonic stem cells using the “Yamanaka factors,” a cocktail of genes encoding four different transcription factors.1 Constitutive expression of the Yamanaka factors in genetically altered mice causes cancer, but controlled, intermittent expression of three or four of them forestalls aging phenotypes and extends mouse lifespan, evidently by slowing or reversing cellular aging.2 Expressing the Yamanaka factors through viral vectors in mice shows promise in targeted maladies, such as age-related decrements in vision,3 but the path toward safe, systemic intervention in humans will be more difficult.
We have also avoided recent, potentially exciting strategies that may face significant barriers to their utility in humans. Prominent among these is the genetic intervention first shown to turn adult somatic cells into embryonic stem cells using the “Yamanaka factors,” a cocktail of genes encoding four different transcription factors.1 Constitutive expression of the Yamanaka factors in genetically altered mice causes cancer, but controlled, intermittent expression of three or four of them forestalls aging phenotypes and extends mouse lifespan, evidently by slowing or reversing cellular aging.2 Expressing the Yamanaka factors through viral vectors in mice shows promise in targeted maladies, such as age-related decrements in vision,3 but the path toward safe, systemic intervention in humans will be more difficult. More recently, chemical reprogramming cocktails that reverse aspects of aging in old and senescent cells, have opened the possibility of reprograming cells in vivo to rejuvenate tissues by injecting or ingesting small molecules.4 Another approach that has less data but shows promise is SGLT2 inhibition, which seems to prevent heart and kidney diseases, reduce overall mortality in diabetic mice and reduce cardiovascular death in humans.5