The effect of aging on the autophagic and heat shock response in human peripheral blood mononuclear cells

Abstract

Autophagy is a lysosome degradation pathway through which damaged organelles and macromolecules are degraded within the cell. A decrease in activity of the autophagic process has been linked to several age-associated pathologies, including triglyceride accumulation, mitochondrial dysfunction, muscle degeneration, and cardiac malfunction. Here, we examined the differences in the autophagic response using autophagy-inducer rapamycin (Rapa) in peripheral blood mononuclear cells (PBMCs) from young (21.8 ± 1.9 years) and old (64.0 ± 3.7 years) individuals. Furthermore, we tested the interplay between the heat shock response and autophagy systems. Our results showed a significant increase in LC3-II protein expression in response to Rapa treatment in young but not in old individuals. This was associated with a decreased response in MAP1LC3B mRNA levels, but not SQSTM1/p62. Furthermore, HSPA1A mRNA was upregulated only in young individuals, despite no differences in HSP70 protein expression. The combined findings suggest a suppressed autophagic response following Rapa treatment in older individuals.

Metformin Enhances Autophagy and Normalizes Mitochondrial Function to Alleviate Aging-Associated Inflammation

“…The previously unappreciated Th17 cytokine profile that defined T cell inflammation in lean, healthy sexagenarians is strikingly similar to the Th17 profile that dominates inflammation in middle-aged people with obesity-associated T2D (Ip et al, 2016) and in periodontal disease (Abusleme and Moutsopoulos, 2017). Other age-related changes, like autophagy dysfunction and redox imbalance, are also characteristic of cells from metabolically compromised people (McCormick et al, 2018;Gautam et al, 2010). These cell-intrinsic changes, alone or in association with secreted Th17 cytokines, raise the possibility that mechanisms amenable to drug intervention drive the increased risk of T2D with age (Defronzo, 1979;Chen et al, 1985;Davidson, 1979) in addition to age-related (currently non-druggable) changes in adipose tissue distribution.…”

“Diet and Exercise Will Help You Live Longer”: The Meme that Turns on Housekeeping Genes

“…Decrements in autophagic function occur with advancing age; this has been observed in numerous organs and tissues in several model species, including humans [28,66,67]. The loss of autophagic clearance likely precipitates the progressive accrual of damaged proteins and organelles and likely contributes to the aging phenotype [5,6].…”

“…Autophagy function declines with aging which is associated with agerelated pathologies. [4,28,66,67]. An enhancement in autophagic function likely explains, at least in part, the robust effects of regular exercise on age-related health and longevity.…”

Salivary dysfunction caused by medication usage

“…This paper was published as part of the "Translational Geroscience" initiative of Physiology International [51][52][53][54][55][56][57][58][59][60][61].…”