Preventing aging with stem cell rejuvenation: Feasible or infeasible?

Abstract

Characterized by dysfunction of tissues, organs, organ systems and the whole organism, aging results from the reduced function of effective stem cell populations. Recent advances in aging research have demonstrated that old tissue stem cells can be rejuvenated for the purpose of maintaining the old-organ function by youthful re-calibration of the environment where stem cells reside. Biochemical cues regulating tissue stem cell function include molecular signaling pathways that interact between stem cells themselves and their niches. Historically, plasma fractions have been shown to contain factors capable of controlling age phenotypes; subsequently, signaling pathways involved in the aging process have been identified. Consequently, modulation of signaling pathways such as Notch/Delta, Wnt, transforming growth factor-β, JAK/STAT, mammalian target of rapamycin and p38 mitogen-activated protein kinase has demonstrated potential to rejuvenate stem cell function leading to organismic rejuvenation. Several synthetic agents and natural sources, such as phytochemicals and flavonoids, have been proposed to rejuvenate old stem cells by targeting these pathways. However, several concerns still remain to achieve effective organismic rejuvenation in clinical settings, such as possible carcinogenic actions; thus, further research is still required.

Keywords: Aging; Niche; Rejuvenation; Signaling pathway; Stem cell.

Figure 1

Possible targets for rejuvenating strategy in aging stem cells. Which cell types (i.e., stem, progenitor, cycling and/or senescent) are capable of being rejuvenated and what modulation of signaling pathways can produce such cellular rejuvenation must be identified to make stem cell rejuvenation feasible. mTOR: Mammalian target of rapamycin; NF-κB: Nuclear factor-κB; TGF-β: Transforming growth factor-β; TNF-α: Tumor necrosis factor-α.