Mitochondrial responsibility in ageing process: innocent, suspect or guilty
Guillermo López-Lluch1, Carlos Santos-Ocaña, José Antonio Sánchez-Alcázar
1Centro Andaluz de Biología del Desarrollo, CABD-CSIC, CIBERER, Instituto Carlos III, Universidad Pablo de Olavide, Carretera de Utrera km. 1, 41013, Seville, Spain, glopllu@upo.es.
Abstract:
Ageing is accompanied by the accumulation of damaged molecules in cells due to the injury produced by external and internal stressors. Among them, reactive oxygen species produced by cell metabolism, inflammation or other enzymatic processes are considered key factors. However, later research has demonstrated that a general mitochondrial dysfunction affecting electron transport chain activity, mitochondrial biogenesis and turnover, apoptosis, etc., seems to be in a central position to explain ageing. This key role is based on several effects from mitochondrial-derived ROS production to the essential maintenance of balanced metabolic activities in old organisms. Several studies have demonstrated caloric restriction, exercise or bioactive compounds mainly found in plants, are able to affect the activity and turnover of mitochondria by increasing biogenesis and mitophagy, especially in postmitotic tissues. Then, it seems that mitochondria are in the centre of metabolic procedures to be modified to lengthen life- or health-span. In this review we show the importance of mitochondria to explain the ageing process in different models or organisms (e.g. yeast, worm, fruitfly and mice). We discuss if the cause of aging is dependent on mitochondrial dysfunction of if the mitochondrial changes observed with age are a consequence of events taking place outside the mitochondrial compartment.
Insights
Mitochondrial dysfunction is central to aging, impacting cellular health and metabolism. Interventions targeting mitochondria may extend lifespan and healthspan by enhancing biogenesis and mitophagy.
Area of Science:
- Gerontology
- Cell Biology
- Mitochondrial Biology
Background:
- Cellular damage from stressors, including reactive oxygen species (ROS), accumulates with age.
- Mitochondrial dysfunction, affecting electron transport chain, biogenesis, turnover, and apoptosis, is increasingly recognized as a key factor in aging.
- Mitochondria play a crucial role in cellular metabolism and ROS production, influencing organismal aging.
Purpose of the Study:
- To review the central role of mitochondria in the aging process across various model organisms.
- To discuss whether mitochondrial dysfunction is a cause or consequence of aging.
- To highlight potential therapeutic targets within mitochondria for extending healthspan.
Main Methods:
- Review of existing literature on aging and mitochondrial function.
- Analysis of studies across diverse model organisms (yeast, worm, fruit fly, mice).
- Discussion of the interplay between mitochondrial health and aging phenotypes.
Main Results:
- Mitochondrial dysfunction is implicated in various aging phenotypes.
- Interventions like caloric restriction, exercise, and plant-derived compounds can modulate mitochondrial activity (biogenesis, mitophagy).
- Mitochondria are central to metabolic regulation relevant to aging.
Conclusions:
- Mitochondria are critical determinants of aging, influencing lifespan and healthspan.
- Targeting mitochondrial pathways offers potential for anti-aging interventions.
- Further research is needed to elucidate the causal relationship between mitochondrial dysfunction and aging.
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