In December of 2016, a stimulating scientific paper titled "In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming" stated in its 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."
The four "Yamanaka factors" have been known to induce pluripotency for some time. Forced expression of these four genes has been reported to turn an adult cell into what appears to be a pluripotent stem cell, with all that entails. However, this report illustrates that stem cell differentiation is a continuum. Here, these researcher report that a relatively small dose of these four factors - not enough to induce pluripotency- can prolong lifespan in a mouse model of premature aging, as well as ameliorate age-related impairments in muscle repair in aged mice. The epigenetic remodeling accomplished by this protocol appears promising, and may help us to rejuvenate older humans.
However, we should proceed with caution; these researchers reported that too long of expression of the Yamanaka factors (only 8 days) caused nearly two-thirds of the animals to die, presumably by causing organ failure resulting from too much de-differentiation. While promising, safely striking a balance between rejuvenation and de-differentiation with a similar protocol in humans might be difficult to accomplish.
We invite you to read the paper by clicking on the link below!