Decline in Self-Renewal Factors Contributes to Aging of the Stem Cell Niche in the Drosophila Testis
Open accessAbstract
Aging is characterized by compromised organ and tissue function. A decrease in stem cell number and/or activity could lead to the aging-related decline in tissue homeostasis. We have analyzed how the process of aging affects germ line stem cell (GSC) behavior in the Drosophila testis and report that significant changes within the stem cell microenvironment, or niche, occur that contribute to a decline in stem cell number over time. Specifically, somatic niche cells in testes from older males display reduced expression of the cell adhesion molecule DE-cadherin and a key self-renewal signal unpaired (upd). Loss of upd correlates with an overall decrease in stem cells residing within the niche. Conversely, forced expression of upd within niche cells maintains GSCs in older males. Therefore, our data indicate that age-related changes within stem cell niches may be a significant contributing factor to reduced tissue homeostasis and regeneration in older individuals.
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Lower E-cadherin and Unpaired levels help age the GSC niche by loosening GSC attachment to cap or hub cells.
“Reduced levels of E-cadherin and Unpaired also contribute to aging of GSC niche by weakening the association between GSCs and cap or hub cells; overexpression of these signaling molecules rescues the age-dependent decline in GSC frequency122,153.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [122]
Drosophila cap cells and hub cells become fewer as the flies age.
“In Drosophila, the number of cap cells and hub cells, which serve as support cells for germline stem cells (GSCs) in the testes and ovaries, respectively, decreases with age.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [122]
Boosting these signaling molecules reverses the age-related drop in GSC numbers.
“Reduced levels of E-cadherin and Unpaired also contribute to aging of GSC niche by weakening the association between GSCs and cap or hub cells; overexpression of these signaling molecules rescues the age-dependent decline in GSC frequency122,153.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [122]
When the niche is lost, BMP signaling needed to maintain GSCs is impaired.
“This loss of the stem cell niche impairs bone morphogenetic protein (BMP) signaling from the niche that is necessary for GSC maintenance122,153.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [122]
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Self-citation
- Authors
- Boyle, M., Wong, C., Rocha, M., & Jones, D. L.
- Affiliations
- Salk Institute for Biological Studies (US)
- Corresponding author
- Jones, D. Leanne
- ORCID
- Jones, D. Leanne
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 1
- Issue
- 4
- Pages
- 470-478
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2087025782
- Cited by
- 268
- References
- 41
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 9 · 2023: 6 · 2022: 6 · 2021: 13 · 2020: 12 · 2019: 19 · 2018: 10 · 2017: 6 · 2016: 15 · 2015: 19 · 2014: 21 · 2013: 17 · 2012: 26
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG028092)
- 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 › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- stem cell aging, germline stem cells, testis, stem cell niche, self-renewal, DE-cadherin, niche cells, tissue homeostasis, Drosophila
- MeSH terms
- Animals, Cell Division, Drosophila melanogaster, Male, Spermatogenesis, Stem Cells, Testis, Signal Transduction, Cellular Senescence, Drosophila Proteins, Cell Proliferation, STAT Transcription Factors, Janus Kinases
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