Role of epigenetic factors during blockade of the renin-angiotensin system across aging

In the present article, we aimed to determine whether the beneficial effects of renin-angiotensin system (RAS) blockade on aging involve epigenetic changes and the participation of any of the cell-rejuvenating Yamanaka factors. To this end, we have reviewed published work that investigated aging and its relation to epigenetic modifications, the effects of RAS blockade on aging and epigenetics, RAS's influence on stem cell function, and RAS interactions with the Yamanaka factors KLF4, Oct4, c-Myc, and Sox2. The reviewed information indicates that it is reasonable to propose that RAS inhibition during aging will promote stem cell self-renewal by counteracting the damaging effects of tissue RAS overactivation. Also, experimental data showed that angiotensin II (ANG II) type I receptor blockade reverses the deleterious epigenetic changes promoted by ANG II overactivation. RAS blockade was shown to directly or indirectly affect the expression of the Yamanaka factors. Solid data on the interaction between RAS and the latter transcription factors is lacking. Therefore, it can only be speculated that, among other mechanisms, modification of Yamanaka factor's expression contributes to the beneficial actions of RAS blockade in aging. In conclusion, the recently described epigenetic effects of RAS inhibitors lend further support to the concept of repurposing their use as therapeutic agents to counteract the aging process.