Non-uniform ageing is a major associative risk factor for cancer and degenerative diseases and mitochondrial dysfunction is linked to cellular senescence in association with cell cycle arrest, telomerase decline and nucleic acid/lipid/protein oxidation. Indeed, mitochondrial dysfunction comprises a distinct type of cellular senescence; mitochondrial SIRT3 or SIRT5, can induce Mitochondrial Dysfunction Associated-Senescence (MiDAS)

Senescence is a chronological and pathophysiological sequenced event response that restricts mitotic division and thus aberrant proliferation of damaged, infected and/or tumor inducing cells. Because these cells are senescent and exhibit low anabolic currency to present self-produced antigen epitopes as displayed by HLA, they are not targeted by immune responses but rather, may become secretory and induce inflammation by instantiating the Senescence Associated Secretory Phenotype-SASP. Senescence presents with metabolic reprogramming, epigenetic chromatin remodeling, and the secretion of growth factors, signaling molecules, proinflammatory cytokines and chemokines, extra-cellular matrix metallo proteases, nucleotides, exosomes and ionic bursts collectively referred to as SASP.

Both SASP and MiDAS can occur in the CNS during human aging thus generating a remarkably complex-contrarion dual pathophysiological phenotype leading to neurodegeneration or more rarely, certain forms of brain cancer.

Authentic Biochemistry Podcast is produced by Daniel J. Guerra, PhD.  Today's Date: 16 January 2021

Refs.

Trends in Biochemical Sciences Volume 41 Issue 3 Pages 207-209 (March 2016)

Cell Metabolism Volume 23, Issue 2, 9 February 2016, Pages 303-314

Front. Immunol., 19 March 2018