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In Vitro and In Vivo Detection of Mitophagy in Human Cells, C. Elegans, and Mice
Published on: November 22, 2017
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Mitophagy and DNA damage signaling in human aging
Mansi Babbar1, Sambuddha Basu1, Beimeng Yang1
1Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Mechanisms of Ageing and Development
|January 11, 2020
Summary
Aging impairs mitochondrial quality control, specifically mitophagy, and DNA repair. Intervening in these processes, such as with NAD+ supplementation, may combat age-related diseases and improve longevity.
Area of Science:
- Gerontology
- Molecular Biology
- Cellular Biology
Background:
- Aging is linked to numerous pathologies, with mitochondrial homeostasis playing a key role in age-related diseases and longevity.
- Mitochondrial homeostasis relies on the balance of mitochondrial generation, biogenesis, and removal of dysfunctional mitochondria through mitophagy.
- Both DNA damage/repair and mitophagy are implicated in aging, but their interplay remains unclear.
Purpose of the Study:
- To review the molecular signaling pathways regulating DNA damage and repair.
- To review the molecular signaling pathways regulating mitophagy.
- To highlight potential clinical interventions targeting these pathways for aging.
Main Methods:
- Literature review of molecular signaling pathways in DNA damage/repair and mitophagy.
- Analysis of the interplay between DNA damage, repair, and mitophagy in aging.
- Exploration of NAD+ supplementation as an intervention strategy.
Main Results:
- Mitophagy efficiency declines with age, leading to dysfunctional mitochondria accumulation.
- This accumulation exacerbates age-related disorders like neurodegeneration, inflammation, cancer, and diabetes.
- NAD+ supplementation is identified as a promising intervention targeting both DNA repair and mitophagy.
Conclusions:
- Dysfunctional mitophagy and DNA repair defects are critical drivers of age-related diseases.
- Targeting mitophagy presents a therapeutic opportunity for age-associated conditions.
- NAD+ supplementation offers a potential strategy to improve healthspan by addressing both DNA integrity and mitochondrial quality control.
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