Mitochondrial proteostasis as a shared characteristic of slowed aging: the importance of considering cell proliferation

J Physiol. 2017 Oct 15;595(20):6401-6407. doi: 10.1113/JP274335. Epub 2017 Aug 10.


Proteostasis is one of the seven "pillars of aging research" identified by the Trans-NIH Geroscience Initiative and loss of proteostasis is associated with aging and age-related chronic disease. Accumulated protein damage and resultant cellular dysfunction are consequences of limited protein repair systems and slowed protein turnover. When relatively high rates of protein turnover are maintained despite advancing age, damaged proteins are more quickly degraded and replaced, maintaining proteome fidelity. Therefore, maintenance of protein turnover represents an important proteostatic mechanism. However, measurement of protein synthesis without consideration for cell proliferation can result in an incomplete picture, devoid of information about how new proteins are being allocated. Simultaneous measurement of protein and DNA synthesis provides necessary mechanistic insight about proteins apportioned for newly proliferating cells versus for somatic maintenance. Using this approach with a number of murine models of slowed aging shows that, compared to controls, energetic resources are directed more toward somatic maintenance and proteostasis, and away from cell growth and proliferation. In particular, slowed aging models are associated with heightened mechanisms of mitochondrial proteostatic maintenance. Taking cell proliferation into account may explain the paradoxical findings that aging itself and slowed aging interventions can both be characterized by slower rates of protein synthesis.

Keywords: aging; mitochondria; proteostasis; somatic maintenance.

Publication types

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

MeSH terms

  • Aging / metabolism*
  • Animals
  • Cell Proliferation
  • Humans
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / metabolism*
  • Proteostasis*


  • Mitochondrial Proteins