Biphasic Modeling of Mitochondrial Metabolism Dysregulation during Aging

Darren J. Baker, Shahaf Peleg

Research output: Contribution to journalReview articlepeer-review

21 Scopus citations


Organismal aging is classically viewed as a gradual decline of cellular functions and a systemic deterioration of tissues that leads to an increased mortality rate in older individuals. According to the prevailing theory, aging is accompanied by a continuous and progressive decline in mitochondrial metabolic activity in cells. However, the most robust approaches to extending healthy lifespan are frequently linked with reduced energy intake or with lowering of mitochondrial activity. While these observations appear contradictory, recent work and technological advances demonstrate that metabolic deregulation during aging is potentially biphasic. In this Opinion we propose a novel framework where middle-age is accompanied by increased mitochondrial activity that subsequently declines at advanced ages. Classically, mitochondria-associated metabolic activity is believed to decrease gradually during aging. By contrast, caloric restriction and lowering of metabolic rates are robust methods to increase healthy lifespan. Recent data support a biphasic model of age-associated mitochondrial dysregulation in which metabolism is increased from young adult to middle-age and subsequently reduced in later stages of life. Epigenetic alterations are metabolic modifications of proteins (histones) that locally remodel chromatin and therefore may mirror the biphasic changes in metabolism during aging. Middle-age-associated metabolic increase may be causally linked with the induction of senescence in cells, as these cells are characterized by increased metabolic activity.

Original languageEnglish (US)
Pages (from-to)702-711
Number of pages10
JournalTrends in biochemical sciences
Issue number9
StatePublished - Sep 2017


  • aging
  • epigenetics
  • metabolism
  • mitochondria
  • senescence

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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