Resolving Geroplasticity to the Balance of Rejuvenins and Geriatrins.

According to the cell centric hypotheses, the deficits that drive aging occur within cells by age dependent progressive damage to organelles, telomeres, biologic signaling pathways, bioinformational molecules, and by exhaustion of stem cells. Here, we amend these hypotheses and propose an eco-centric model for geroplasticity (aging plasticity including aging reversal). According to this model, youth and aging are plastic and require constant maintenance, and, respectively, engage a host of endogenous rejuvenating (rejuvenins) and gero-inducing [geriatrin] factors. Aging in this model is akin to atrophy that occurs as a result of damage or withdrawal of trophic factors. Rejuvenins maintain and geriatrins adversely impact cellular homeostasis, cell fitness, and proliferation, stem cell pools, damage response and repair. Rejuvenins reduce and geriatrins increase the age-related disorders, inflammatory signaling, and senescence and adjust the epigenetic clock. When viewed through this perspective, aging can be successfully reversed by supplementation with rejuvenins and by reducing the levels of geriatrins.