September 1, 2018

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.

PMID: 30269563 | DOI: 10.1556/2060.105.2018.3.20