Role of Carbonyl Modifications on Aging-Associated Protein Aggregation

Sci Rep. 2016 Jan 18;6:19311. doi: 10.1038/srep19311.

Abstract

Protein aggregation is a common biological phenomenon, observed in different physiological and pathological conditions. Decreased protein solubility and a tendency to aggregate is also observed during physiological aging but the causes are currently unknown. Herein we performed a biophysical separation of aging-related high molecular weight aggregates, isolated from the bone marrow and splenic cells of aging mice and followed by biochemical and mass spectrometric analysis. The analysis indicated that compared to younger mice an increase in protein post-translational carbonylation was observed. The causative role of these modifications in inducing protein misfolding and aggregation was determined by inducing carbonyl stress in young mice, which recapitulated the increased protein aggregation observed in old mice. Altogether our analysis indicates that oxidative stress-related post-translational modifications accumulate in the aging proteome and are responsible for increased protein aggregation and altered cell proteostasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Aging / pathology
  • Animals
  • Bone Marrow Cells / metabolism
  • Female
  • Mice
  • Oxidative Stress
  • Protein Aggregates*
  • Protein Aggregation, Pathological
  • Protein Carbonylation*
  • Proteins / metabolism*
  • Reactive Oxygen Species / metabolism
  • Spleen / metabolism

Substances

  • Protein Aggregates
  • Proteins
  • Reactive Oxygen Species