An Example of the Relevance of Autophagy
Time and again, autophagy, the process by which cells recycle their broken machinery, shows up as being important in methods of altering life span in lower animals: "The acetylase inhibitor, spermidine, and the deacetylase activator, resveratrol, both induce autophagy and prolong life span of the model organism Caenorhabditis elegans in an autophagy-dependent fashion. Based on these premises, we investigated the differences and similarities in spermidine and resveratrol-induced autophagy. The deacetylase sirtuin 1 (SIRT1) and its orthologs are required for the autophagy induction by resveratrol but dispensable for autophagy stimulation by spermidine ... SIRT1 is also dispensable for life span extension by spermidine. Mass spectrometry analysis of the human acetylproteome revealed that resveratrol and/or spermidine induce changes in the acetylation of 560 peptides corresponding to 375 different proteins. Among these, 170 proteins are part of the recently elucidated human autophagy protein network. Importantly, spermidine and resveratrol frequently affect the acetylation pattern in a similar fashion. In the cytoplasm, spermidine and resveratrol induce convergent protein de-acetylation more frequently than convergent acetylation, while in the nucleus, acetylation is dominantly triggered by both agents. We surmise that subtle and concerted alterations in the acetylproteome regulate autophagy at multiple levels."