Mitochondrial and metabolic dysfunction in ageing and age-related diseases

By J. Amorim, G. Coppotelli, A. Rolo, C. Palmeira, J. M. Ross, D. Sinclair. Nature Reviews Endocrinology, 2022

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Organismal ageing is accompanied by progressive loss of cellular function and systemic deterioration of multiple tissues, leading to impaired function and increased vulnerability to death. Mitochondria have become recognized not merely as being energy suppliers but also as having an essential role in the development of diseases associated with ageing, such as neurodegenerative and cardiovascular diseases. A growing body of evidence suggests that ageing and age-related diseases are tightly related to an energy supply and demand imbalance, which might be alleviated by a variety of interventions, including physical activity and calorie restriction, as well as naturally occurring molecules targeting conserved longevity pathways. Here, we review key historical advances and progress from the past few years in our understanding of the role of mitochondria in ageing and age-related metabolic diseases. We also highlight emerging scientific innovations using mitochondria-targeted therapeutic approaches. This Review discusses the role of mitochondria in metabolism and how mitochondria contribute to age-related metabolic diseases. This knowledge might guide us in designing therapies targeting metabolic disorders to extend human health span and lifespan. The rate of ageing is coordinated, at least in part, by conserved genetic and biochemical pathways. A complex network of interactions between longevity pathways reveals an intricate regulation of mitochondrial physiology during ageing. Cellular metabolism interconnects the nine hallmarks of ageing, and deregulation of energy metabolism by environmental variations is an essential process leading to mitochondrial dysfunction during ageing. A better understanding of mitochondrial dysfunction during ageing and age-related metabolic diseases will provide fundamental knowledge to develop therapies to combat late-life morbidities. Human longitudinal studies will be essential to understand individuals’ risk of diseases much earlier in life, and will inform health choices and medical care options. The rate of ageing is coordinated, at least in part, by conserved genetic and biochemical pathways. A complex network of interactions between longevity pathways reveals an intricate regulation of mitochondrial physiology during ageing. Cellular metabolism interconnects the nine hallmarks of ageing, and deregulation of energy metabolism by environmental variations is an essential process leading to mitochondrial dysfunction during ageing. A better understanding of mitochondrial dysfunction during ageing and age-related metabolic diseases will provide fundamental knowledge to develop therapies to combat late-life morbidities. Human longitudinal studies will be essential to understand individuals’ risk of diseases much earlier in life, and will inform health choices and medical care options.

Subfields: Aging, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/71bb301316680bd24c63e75b2b9b8b48c533b656

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Citations in the corpus

• Mitochondrial dysfunction: mechanisms and advances in therapy (2024, background): “25,260 Both mtDNA point mutations and deletions in somatic cells have been shown to accumulate with age, thereby driving energy exhaustion and oxidative damage.”