Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog
Open accessAbstract
In mammals, the PGC-1 transcriptional coactivators are key regulators of energy metabolism, including mitochondrial biogenesis and respiration, which have been implicated in numerous pathogenic conditions, including neurodegeneration and cardiomyopathy. Here, we show that overexpression of the Drosophila PGC-1 homolog (dPGC-1/spargel) is sufficient to increase mitochondrial activity. Moreover, tissue-specific overexpression of dPGC-1 in stem and progenitor cells within the digestive tract extends life span. Long-lived flies overexpressing dPGC-1 display a delay in the onset of aging-related changes in the intestine, leading to improved tissue homeostasis in old flies. Together, these results demonstrate that dPGC-1 can slow aging both at the level of cellular changes in an individual tissue and also at the organismal level by extending life span. Our findings point to the possibility that alterations in PGC-1 activity in high-turnover tissues, such as the intestine, may be an important determinant of longevity in mammals.
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Stem cell exhaustion may be driven by an imbalance between quiescence and proliferation.
“Stem cell exhaustion may also be driven by an imbalance of stem cell quiescence and proliferation.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [109]
A proper quiescence-proliferation balance is needed to keep the stem cell pool available for repeated tissue regeneration, as shown in Drosophila intestine, HSCs and p21-null neural stem cells.
“Maintaining this balance is crucial to sustain the stem cell pool through multiple rounds of tissue regeneration, as demonstrated by studies in the Drosophila intestine, and in HSCs and neural stem cells of p21-null mice109,130,131.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [109]
When cell cycle control is lost, too much proliferation speeds up depletion of these stem cell pools.
“Excessive proliferation caused by loss of cell cycle regulation results in accelerated exhaustion of these stem cell pools.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [109]
Age-related changes in PGC-1α activity contribute to loss of mitochondrial biogenesis and function.
“changes in the activity of the transcription activator PGC-1α with age contribute to the loss of mitochondrial biogenesis and function (Rera et al., 2011; Sun et al., 2016).”
From The Aging Epigenome (2016) · cites this paper as Rera et al., 2011
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- Authors
- Rera, M., Bahadorani, S., Cho, J., Koehler, C. L., Ulgherait, M., Hur, J. H., Ansari, W. S., Lo, T., Jones, D. L., & Walker, D. W.
- Affiliations
- University of California, Los Angeles (US)
- Salk Institute for Biological Studies (US)
- University of California San Diego (US)
- Corresponding author
- Jones, D. Leanne
- Walker, David W.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 14
- Issue
- 5
- Pages
- 623-634
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC3238792
- OpenAlex
- W2113431427
- Cited by
- 472
- References
- 54
- Citations by year
- 2026: 23 · 2025: 32 · 2024: 44 · 2023: 33 · 2022: 40 · 2021: 38 · 2020: 32 · 2019: 29 · 2018: 39 · 2017: 29 · 2016: 29 · 2015: 34 · 2014: 30 · 2013: 23 · 2012: 14
- FWCI
- 8.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Funders
- National Institute on Aging (R01AG040288, P30AG028748, R01AG028092, R01AG037514)
- National Institute of General Medical Sciences (GM-07185, T32GM007185)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007495)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- PGC-1, Drosophila, longevity, aging, lifespan extension, tissue homeostasis, intestinal stem cells, progenitor cells, mitochondrial biogenesis, mitochondrial activity, energy metabolism, transcriptional coactivator
- MeSH terms
- Animals, Drosophila melanogaster, Energy Metabolism, Female, Glucose, Homeostasis, Intestinal Mucosa, Intestines, Longevity, Male, Mammals, Mitochondria, Organ Specificity, Stem Cells, Transcription Factors, Gene Expression, Sequence Homology, Amino Acid, Cell Respiration, Drosophila Proteins, Positive Transcriptional Elongation Factor B, Mice
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