Longevity-relevant regulation of autophagy at the level of the acetylproteome.
Level 5 - mechanism / opinion, no new human data
Preclinical in vitro and non-mammalian model organism study without human in vivo data.
PubMed 21460620 · doi:10.4161/auto.7.6.15191
What was done
Investigated the mechanisms of autophagy induction and lifespan extension by the acetylase inhibitor spermidine and the deacetylase activator resveratrol in human cell lines, Saccharomyces cerevisiae, and Caenorhabditis elegans. The authors assessed the requirement of sirtuin 1 (SIRT1) and analyzed alterations in the human acetylproteome using mass spectrometry.
What was found
SIRT1 and its orthologs were necessary for resveratrol-induced autophagy, but dispensable for spermidine-induced autophagy and lifespan extension. Mass spectrometry of human cells showed that spermidine and/or resveratrol altered the acetylation of 560 peptides across 375 proteins, including 170 proteins within the known human autophagy network. Both compounds promoted convergent de-acetylation in the cytoplasm and convergent acetylation in the nucleus. Specific quantitative effect sizes or statistical thresholds were not reported in the abstract.
Why it matters
The study outlines how distinct upstream longevity-associated compounds converge on common post-translational acetylation programs to regulate autophagy.
Limits
Findings are limited to cell culture and model organisms, with no in vivo human testing. The abstract omits specific dosages, effect magnitudes, and statistical significance values.
Cited by
- supports During complete caloric starvation, cytoplasmic protein deacetylation occurs across all major cell types throughout the body, except in the brain which is buffered against this effect.