Causal roles of mitochondrial dynamics in longevity and healthy aging

EMBO Rep. 2019 Dec 5;20(12):e48395. doi: 10.15252/embr.201948395. Epub 2019 Oct 31.

Abstract

Mitochondria are organized in the cell in the form of a dynamic, interconnected network. Mitochondrial dynamics, regulated by mitochondrial fission, fusion, and trafficking, ensure restructuring of this complex reticulum in response to nutrient availability, molecular signals, and cellular stress. Aberrant mitochondrial structures have long been observed in aging and age-related diseases indicating that mitochondrial dynamics are compromised as cells age. However, the specific mechanisms by which aging affects mitochondrial dynamics and whether these changes are causally or casually associated with cellular and organismal aging is not clear. Here, we review recent studies that show specifically how mitochondrial fission, fusion, and trafficking are altered with age. We discuss factors that change with age to directly or indirectly influence mitochondrial dynamics while examining causal roles for altered mitochondrial dynamics in healthy aging and underlying functional outputs that might affect longevity. Lastly, we propose that altered mitochondrial dynamics might not just be a passive consequence of aging but might constitute an adaptive mechanism to mitigate age-dependent cellular impairments and might be targeted to increase longevity and promote healthy aging.

Keywords: aging; fission; fusion; mitochondria; mitochondrial dynamics.

Publication types

  • Review

MeSH terms

  • AMP-Activated Protein Kinases / physiology
  • Aging / physiology
  • Animals
  • Cellular Senescence / physiology
  • Healthy Aging / physiology*
  • Host Microbial Interactions / physiology
  • Humans
  • Insulin / physiology
  • Longevity / physiology*
  • Microbiota / physiology
  • Mitochondrial Dynamics / physiology*
  • Models, Biological
  • Organelles / physiology
  • Signal Transduction
  • Sirtuins / physiology
  • Somatomedins / physiology
  • TOR Serine-Threonine Kinases / physiology

Substances

  • Insulin
  • Somatomedins
  • TOR Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Sirtuins