Macroautophagy is impaired in old murine brain tissue as well as in senescent human fibroblasts

Redox Biol. 2016 Dec;10:266-273. doi: 10.1016/j.redox.2016.10.015. Epub 2016 Oct 26.

Abstract

The overall decrease in proteolytic activity in aging can promote and accelerate protein accumulation and metabolic disturbances. To specifically analyze changes in macroautophagy (MA) we quantified different autophagy-related proteins (ATGs) in young, adult and old murine tissue as well as in young and senescent human fibroblasts. Thus, we revealed significantly reduced levels of ATG5-ATG12, LC3-II/LC3-I ratio, Beclin-1 and p62 in old brain tissue and senescent human fibroblasts. To investigate the role of mTOR, the protein itself and its target proteins p70S6 kinase and 4E-BP1 were quantified. Significant increased mTOR protein levels were determined in old tissue and cells. Determination of phosphorylated and basal amount of both proteins suggested higher mTOR activity in old murine tissue and senescent human fibroblasts. Besides the reduced levels of ATGs, mTOR can additionally reduce MA, promoting further acceleration of protein accumulation and metabolic disturbances during aging.

Keywords: ATGs; Aging; Autophagy-lysosome pathway; Fibroblasts; MTOR; Senescence.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Aging / metabolism*
  • Animals
  • Autophagy*
  • Autophagy-Related Proteins / metabolism*
  • Brain / metabolism*
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins
  • Cellular Senescence
  • Down-Regulation
  • Eukaryotic Initiation Factors
  • Fibroblasts / cytology*
  • Fibroblasts / metabolism
  • Gene Expression Regulation, Developmental
  • Humans
  • Male
  • Mice
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Autophagy-Related Proteins
  • Carrier Proteins
  • Cell Cycle Proteins
  • EIF4EBP1 protein, human
  • Eif4ebp1 protein, mouse
  • Eukaryotic Initiation Factors
  • Phosphoproteins
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases