CISD2 Upregulation Reduces the Senescence-Associated Secretory Phenotype in Aged Skin

CISD2 expression declines with age, while upregulation of CISD2 expression has been shown in mice to improve liver function and extend life span. This strategy is expected to have broad effects on function in many tissues beyond the liver. At least some of those benefits result from an increase in the efficiency of the complex cell maintenance processes of autophagy, recycling damaged and unwanted proteins and cell structures. As is the case for other approaches to slowing aging that function via autophagy, CISD2 upregulation has the effect of reducing senescent cell burden and suppressing the harmful senescence-associated secretory phenotype (SASP). Researchers here demonstrate this benefit in aged skin. CDGSH iron-sulfur domain-containing protein 2 (CISD2), a pro-longevity gene, mediates healthspan in mammals. CISD2 is down-regulated during aging. Furthermore, a persistently high level of CISD2 promotes longevity and ameliorates an age-related skin phenotype in transgenic mice. Here we translate the genetic evidence into a pharmaceutical application using a potent CISD2 activator, hesperetin, which enhances CISD2 expression in HEK001 human keratinocytes from an older person. We also treated naturally aged mice in order to study the activator's anti-aging efficacy. We studied the biological effects of hesperetin on aging skin using, firstly, a cell-based platform, namely a HEK001 human keratinocyte cell line established from an older person. Secondly, we used...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs