The coordination of nuclear and mitochondrial communication during aging and calorie restriction
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Mitochondria are dynamic organelles that integrate environmental signals to regulate energy production, apoptosis and Ca(2+) homeostasis. Not surprisingly, mitochondrial dysfunction is associated with aging and the pathologies observed in age-related diseases. The vast majority of mitochondrial proteins are encoded in the nuclear genome, and so communication between the nucleus and mitochondria is essential for maintenance of appropriate mitochondrial function. Several proteins have emerged as major regulators of mitochondrial gene expression, capable of increasing transcription of mitochondrial genes in response to the physiological demands of the cell. In this review, we will focus on PGC-1alpha, SIRT1, AMPK and mTOR and discuss how these proteins regulate mitochondrial function and their potential involvement in aging, calorie restriction and age-related disease. We will also discuss the pathways through which mitochondria signal to the nucleus. Although such retrograde signaling is not well studied in mammals, there is growing evidence to suggest that it may be an important area for future aging research. Greater understanding of the mechanisms by which mitochondria and the nucleus communicate will facilitate efforts to slow or reverse the mitochondrial dysfunction that occurs during aging.
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PGC-1α and PGC-1β activity decreases across ageing tissues.
“the activity of the master mitochondrial regulators PGC-1α and PGC-1β decreases across ageing tissues7,8.”
From Telomere dysfunction induces metabolic and mitochondrial compromise (2011) · cites this paper as [7]
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ON THE INFLUENCE OF FOOD AND TEMPERATURE UPON THE DURATION OF LIFE
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Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C. elegans
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Mutant mice lacking acetyl-CoA carboxylase 1 are embryonically lethal
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cDNA Cloning and mRNA Analysis of PGC-1 in Epitrochlearis Muscle in Swimming-Exercised Rats
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Mitochondrial Transcription Factor A Induction by Redox Activation of Nuclear Respiratory Factor 1
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Aging and the Role of Reactive Nitrogen Species
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PGC-1β in the Regulation of Hepatic Glucose and Energy Metabolism
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“In contrast, it appears that an increase in activity of Snf1p, the yeast homolog of AMPK, causes accelerated aging by increasing recombination at rDNA loci and encouraging the formation of extrachromsomal rDNA circles (ERC) (Ashrafi et al., 2000; Lin et al., 2003b).”
BackgroundProgressive loss of SIRT1 with cell cycle withdrawal
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Flagged first, then by citations
Cited by
Sorted by citations
Telomere dysfunction induces metabolic and mitochondrial compromise
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The role of mitochondria in aging
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AMPK and SIRT1: a long-standing partnership?
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Sirtuin regulation of mitochondria: energy production, apoptosis, and signaling
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The hallmarks of fibroblast ageing
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MOTS-c: a novel mitochondrial-derived peptide regulating muscle and fat metabolism
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Metabolic features and regulation in cell senescence
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“restore mitochondrial function, activate an alternative energy supply, modify cellular function, and change cellular fate to death, senescence, or proliferation (42, 44-47).”
BackgroundInfluentialFinley, L. W. S., Lee, J., Souza, A., Desquiret-Dumas, V., Bullock, K., Rowe, G. C., Procaccio, V., Clish, C. B., Arany, Z., & Haigis, M. C. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1115813109 · Cited by 102 · see citing works
Self-citationMitochondrial function and mitochondrial DNA maintenance with advancing age
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- Authors
- Finley, L. W. S., & Haigis, M. C.
- Affiliations
- Harvard University (US)
- Corresponding author
- Haigis, Marcia C.
- Venue
- Ageing Research Reviews
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 8
- Issue
- 3
- Pages
- 173-188
- ISSN
- 1568-1637 (ISSN-L)
- PMC
- PMC4702504
- OpenAlex
- W2049547722
- Cited by
- 207
- References
- 270
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 10 · 2020: 15 · 2019: 6 · 2018: 9 · 2017: 8 · 2016: 9 · 2015: 14 · 2014: 22 · 2013: 29 · 2012: 20
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Ageing Research Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG032375)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- mitochondrial-nuclear communication, mitochondrial dysfunction, aging, caloric restriction, PGC-1α, SIRT1, AMPK, mTOR, mitochondrial gene expression, retrograde signaling, age-related diseases, mitochondrial biogenesis
- MeSH terms
- Aging, Animals, Cell Nucleus, Gene Expression Regulation, Humans, Mitochondria, Signal Transduction, Cellular Senescence, Active Transport, Cell Nucleus, Mitochondrial Proteins, Mitochondrial Diseases, Caloric Restriction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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