Autophagy and senescence: A new insight in selected human diseases

Abstract

Senescence and autophagy play important roles in homeostasis. Cellular senescence and autophagy commonly cause several degenerative processes, including oxidative stress, DNA damage, telomere shortening, and oncogenic stress; hence, both events are known to be interrelated. Autophagy is well known for its disruptive effect on human diseases, and it is currently proposed to have a direct effect on triggering senescence and quiescence. However, it is yet to be proven whether autophagy has a positive or negative impact on senescence. It is known that elevated levels of autophagy induce cell death, whereas inadequate autophagy can trigger cellular senescence. Both have important roles in human diseases such as aging, renal degeneration, neurodegenerative disorders, and cancer. Therefore, this review aims to highlight the relevance of senescence and autophagy in selected human ailments through a summary of recent findings on the connection and effects of autophagy and senescence in these diseases. arthritis, autophagy, cancer, cardiac diseases, renal diseases, senescenceAbbreviations: 3-MA, 3-methyladenine; ATG, autophagy related; ATM, ataxia-telangiectasia mutated; BNIP3, BCL2-interacting protein 3; CDKN1A/p21, cyclin-dependent kinase inhibitor 1A;LAMP-1, lysosome-associated membrane glycoprotein-1; LC3, light chain 3; MiT/TFE, microphthalmia/transcription factor E; mtor, mammalian target of rapamycin; OA, osteoarthritis; PTECs, proximal tubular epithelial cells; RAPTOR, regulatory-associated protein; SASP, senescence-associated secretory phenotype; TP53, tumor protein p53; VSMCs, vascular smooth muscle cells.*Peramaiyan Rajendran and Abdullah M Alzahrani contributed equally to this work.

Liver osteopontin is required to prevent the progression of age‐related nonalcoholic fatty liver disease

“…Considering that deficient autophagy in the liver impairs the mobilization of TGs into FAs, resulting in steatosis (Singh et al., 2009) and that it could have a direct effect on triggering senescence and quiescence (Rajendran et al., 2019), we analyzed levels of proteins involved in autophagy. We found no statistically significant differences in ATG5, ATG7, or LC3 levels in 10m OPN‐KO mice (Figure C).…”

Autophagy inhibits the mesenchymal stem cell aging induced by D‐galactose through ROS/JNK/p38 signalling

“…Under physiological conditions, autophagy can maintain the normal physiological functions of cells by eliminating damaged organelles and biomacromolecules . However, the autophagy activity of a cell is enhanced by some stresses (eg, nutritional deficiency and ischaemia) and degrades cell components and releases free amino and fatty acids, which can supplement energies, promote biomacromolecule synthesis, maintain cell survival, promote cell homeostasis, and promote adaptation to stress . Autophagy not only plays an important regulatory role in body aging and cell aging but also participates in the initiation and development of multiple geriatric diseases .…”

Insights from In Vivo Studies of Cellular Senescence

“…Other types of metabolic dysfunction, such as mitochondrial dysfunction, ER stress, and autophagy impairment have been implicated in senescence and discussed recently elsewhere [45][46][47][48]. Interestingly, it was found that knockdown of LSG1, a GTPase in charge of the biogenesis of the 60S ribosomal subunit, caused the perturbation of the endoplasmic reticulum homeostasis leading the cell to a senescent state [48].…”