Freitag, 30. Oktober 2015

Stress resistance, Proteostasis and Aging reviewed (2015)


Let's start with a brief literature review by Alper, Bronikowski and Harper 2015 (1). I have excerpted some particularly noteworthy passages.

CR does not lead to epigenetically stable programming, hence an ex vivo model of CR has been hard to come by:
Interestingly, cells grown from dietary models of life extension fail to show this correlation. More specifically, dermal fibroblasts from mice subjected to life-long caloric restriction (CR) or provided with a diet low in the essential amino acid methionine, were no more stress resistant to multiple cytotoxins relative to their normal-fed counterparts (Harper et al., 2006b). Caloric restriction is perhaps the most robust life-extending intervention known (Fontana and Partridge, 2015) while diets low in methionine have been repeatedly shown to increase longevity in both rats and mice (Perrone et al., 2013, Sun et al., 2009 and Miller et al., 2005). A clue to this apparent discrepancy comes from studies using conditioned media; or more specifically, cells exposed to media supplemented with serum collected from rodents undergoing CR are more stress resistant than are cells grown in the presence of normal media alone. This suggests the presence of specific circulating factors needed for the life extending effects of dietary restriction that are lost during the derivation and expansion of individual cell lines (de Cabo et al., 2003 and De Cabo et al., 2015).
Multi-stress resistance correlates with long lifespans but there are exceptions to the rule: