Stochastic non-enzymatic modification of long-lived macromolecules - A missing hallmark of aging

Ageing Res Rev. 2020 Sep;62:101097. doi: 10.1016/j.arr.2020.101097. Epub 2020 Jun 12.

Abstract

Damage accumulation in long-living macromolecules (especially extracellular matrix (ECM) proteins, nuclear pore complex (NPC) proteins, and histones) is a missing hallmark of aging. Stochastic non-enzymatic modifications of ECM trigger cellular senescence as well as many other hallmarks of aging affect organ barriers integrity and drive tissue fibrosis. The importance of it for aging makes it a key target for interventions. The most promising of them can be AGE inhibitors (chelators, O-acetyl group or transglycating activity compounds, amadorins and amadoriases), glucosepane breakers, stimulators of elastogenesis, and RAGE antagonists.

Keywords: AGE inhibitors; Aging; Extracellular matrix; Glucosepane breakers; MRTF; ROCK; YAP/TAZ.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging*
  • Extracellular Matrix
  • Extracellular Matrix Proteins
  • Fibrosis
  • Histones
  • Humans

Substances

  • Extracellular Matrix Proteins
  • Histones