Skin aging is accompanied by an accumulation of senescent cells, which promote a low chronic inflammation and degradation of the extracellular matrix. Autophagy is a conserved biological process involved in cellular homeostasis through the recycling of long-lived or damaged proteins and organelles. Impaired during aging, it has been speculated that autophagy could be involved in senescence. The role of autophagy in the context of cellular senescence remains elusive and is not understood yet,

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... mingly dependent on the cell type, tissue, and manner in which senescence is induced. Why damaged cells resort to senescence instead of apoptosis remains a key question in the understanding of aging and age-related pathologies. In this work, 2D-LC-MS/MS labeling-assisted proteomics identified 230 upregulated and 228 downregulated proteins in senescent normal human dermal fibroblasts (NHDF). When upregulated proteins were subjected to a gene set enrichment analysis (GSEA), 27autophagy-related biological processes were found enriched, showing that stress-induced premature senescence (SIPS) leads to an increased autophagic activity in senescent NHDF. This included biological processes such as lysosome biogenesis, mTOR signaling and macroautophagy. Although autophagy is increased in SIPS, whether it is involved in senescence development or a consequence remained to be clarified. In WS1 human fibroblasts, rapamycin-mediated stimulation of autophagic flux prior to SIPS induction delayed the onset of senescence, whereas its inhibition through chloroquine showed no effect. After SIPS induction, stimulation of autophagy delayed the onset of senescence, whereas its inhibition changed the cell fate from senescence to cell death. The latter observation was further shown to be specific to senescent WS1, suggesting the existence of an autophagy-mediated "apoptotic switch". Although the exact molecular mechanism of this switch remains to be determined, this work implicates mitochondrial abundance and/or mass as well as calcium signaling [...]