Abstract
Aging is the major risk factor for many human diseases. In vitro studies have demonstrated that cellular reprogramming to pluripotency reverses cellular age, but alteration of the aging process through reprogramming has not been directly demonstrated in vivo. Here, we report that partial reprogramming by short-term cyclic expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) ameliorates cellular and physiological hallmarks of aging and prolongs lifespan in a mouse model of premature aging. Similarly, expression of OSKM in vivo improves recovery from metabolic disease and muscle injury in older wild-type mice. The amelioration of age-associated phenotypes by epigenetic remodeling during cellular reprogramming highlights the role of epigenetic dysregulation as a driver of mammalian aging. Establishing in vivo platforms to modulate age-associated epigenetic marks may provide further insights into the biology of aging.
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•Partial reprogramming erases cellular markers of aging in mouse and human cells•Induction of OSKM in progeria mice ameliorates signs of aging and extends lifespan•In vivo reprogramming improves regeneration in 12-month-old wild-type mice
Cellular reprogramming by transient expression of Yamanaka factors ameliorates age-associated symptoms, prolongs lifespan in progeroid mice, and improves tissue homeostasis in older mice.