Long Live Partial Reprogramming

In vivo amelioration of age-associated hallmarks by partial reprogramming.

Ocampo et al

Cell.2016;167:1719–1733.

Aging can be defined as the progressive loss of physiological integrity that leads to tissue dysfunction and increased risk for developing age-associated human pathologies, such as cancer, diabetes mellitus, cardiovascular disorders, and neurodegenerative diseases.¹ Therapeutic strategies to delay or prevent aging are aimed to decrease the deleterious effects of aging and to improve the quality of life in aged individuals and eventually to extend the human life span. In addition, deep molecular understanding of the mechanisms of aging may lead to new treatments for age-related diseases. In line with this, a recent article in Cell² shows that cyclic induction of Yamanaka reprogramming factors in vitro, what the authors called “partial reprogramming,” reduces age-associated features in mouse and human cells. Strikingly, partial reprogramming induced in vivo in a mouse model of premature aging ameliorates some aging-associated hallmarks and extends their prematurely shortened life span. Importantly, these beneficial effects are not accompanied by dedifferentiation or loss of cellular identity. Finally, the authors show that partial in vivo reprogramming increases the regenerative capacity of physiologically aged wild-type mice.

In the past few years, many research efforts to treat age-related pathologies and the effects of physiological aging have been focused on the use of cellular reprogramming strategies.³ In vitro reprogramming of differentiated cells into iPS cells by the expression of the so-called Yamanaka factors (SOX2, OCT4, c-MYC, and KLF4) has the striking capacity to reverse some of the molecular hallmarks associated with aging in cells from healthy normal individuals and in cells from patients with progeria syndromes.^4–6 Thus, it has been shown that cellular reprogramming induces telomerase-mediated telomere elongation and opening of telomeric chromatin (decreased H3K9m3 and H4K20m3 marks, increased telomeric transcription), …