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

Physiol Int. 2018 Sep 1;105(3):247-256. doi: 10.1556/2060.105.2018.3.20. Epub 2018 Oct 1.

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.

Keywords: HSP; PBMC; aging; autophagy; rapamycin.

MeSH terms

  • Adult
  • Aged
  • Aging / physiology*
  • Autophagy / physiology*
  • Female
  • HSP70 Heat-Shock Proteins / metabolism*
  • Humans
  • Leukocytes, Mononuclear / physiology*
  • Male
  • Middle Aged
  • Young Adult

Substances

  • HSP70 Heat-Shock Proteins