Mitochondrial function in ageing: Coordination with signalling and transcriptional pathways

Fei Yin, Harsh Sancheti, Zhigang Liu, Enrique Cadenas

Research output: Contribution to journalReview articlepeer-review

52 Scopus citations

Abstract

Mitochondrial dysfunction entailing decreased energy-transducing capacity and perturbed redox homeostasis is an early and sometimes initiating event in ageing and age-related disorders involving tissues with high metabolic rate such as brain, liver and heart. In the central nervous system (CNS), recent findings from our and other groups suggest that the mitochondrion-centred hypometabolism is a key feature of ageing brains and Alzheimer's disease. This hypometabolic state is manifested by lowered neuronal glucose uptake, metabolic shift in the astrocytes, and alternations in mitochondrial tricarboxylic acid cycle function. Similarly, in liver and adipose tissue, mitochondrial capacity around glucose and fatty acid metabolism and thermogenesis is found to decline with age and is implicated in age-related metabolic disorders such as obesity and type 2 diabetes mellitus. These mitochondrion-related disorders in peripheral tissues can impact on brain functions through metabolic, hormonal and inflammatory signals. At the cellular level, studies in CNS and non-CNS tissues support the notion that instead of being viewed as autonomous organelles, mitochondria are part of a dynamic network with close interactions with other cellular components through energy- or redox-sensitive cytosolic kinase signalling and transcriptional pathways. Hence, it would be critical to further understand the molecular mechanisms involved in the communication between mitochondria and the rest of the cell. Therapeutic strategies that effectively preserves or improve mitochondrial function by targeting key component of these signalling cascades could represent a novel direction for numerous mitochondrion-implicated, age-related disorders.

Original languageEnglish (US)
Pages (from-to)2025-2042
Number of pages18
JournalJournal of Physiology
Volume594
Issue number8
DOIs
StatePublished - Apr 15 2016
Externally publishedYes

ASJC Scopus subject areas

  • Physiology

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