Inflammaging is associated with shifted macrophage ontogeny and polarization in the aging mouse ovary
Open accessAbstract
The fertility of women declines sharply after age 35 and is essentially lost upon menopause at age 51. The ovary plays an important part in aging-associated changes in women’s physiology since it is an essential component of both the reproductive and endocrine systems. Several previous studies in mice have shown that the ovarian tissue goes through drastic changes over the course of aging and exhibits signs of aging-associated chronic inflammation (inflammaging), which may contribute to the marked decline of oocyte quality in aged individuals. To further examine aging-associated gene expression changes in the ovary and to characterize the development of inflammaging, we performed detailed transcriptomic analysis of whole ovaries from mice of six different age groups over the mouse reproductive lifespan and identified more than 5000 genes with significant expression change over the course of aging. Intriguingly, we found aging-associated changes in the expression of several markers that indicate alterations in the composition of ovarian macrophages, which are known to be central players of inflammaging. Using flow cytometry, we analyzed and compared macrophage populations and polarization in young and old ovaries and found a significant increase in monocyte recruitment and macrophage alternative activation (M2) in the old ovaries compared to those in young. Our results are consistent with previous findings of aging-associated increase of fibrosis in the ovarian stromal extracellular matrix, and they provide new clues about the development of inflammaging in the mammalian ovary.
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The ovary exhibits age-dependent inflammation and fibrosis, but whether these are associated with senescence has not been conclusively established.
“Additionally, the ovary exhibits age-dependent inflammation and fibrosis234–237; however, whether these are associated with senescence has not been conclusively established.”
From SenNet recommendations for detecting senescent cells in different tissues (2024) · cites this paper as [237]
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SenNet recommendations for detecting senescent cells in different tissues
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“Additionally, the ovary exhibits age-dependent inflammation and fibrosis 234–237 ; however, whether these are associated with senescence has not been conclusively established.”
Evaluation of inflammation and follicle depletion during ovarian ageing in mice
Lliberos, C., Liew, S. H., Zareie, P., La Gruta, N. L., Mansell, A., & Hutt, K. (2021) · Scientific Reports · doi:10.1038/s41598-020-79488-4 · Cited by 247 · see citing works
- Authors
- Zhang, Z., Schlamp, F., Huang, L., Clark, H., & Brayboy, L.
- Affiliations
- Women & Infants Hospital of Rhode Island (US)
- Cornell University (US)
- Brown University (US)
- Corresponding author
- Brayboy, Lynae
- Venue
- Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-03-01
- Volume
- 159
- Issue
- 3
- Pages
- 325-337
- ISSN
- 1470-1626 (ISSN-L)
- 1741-7899
- PMC
- PMC7066623
- OpenAlex
- W2999824831
- Cited by
- 150
- References
- 80
- Citations by year
- 2026: 24 · 2025: 25 · 2024: 34 · 2023: 19 · 2022: 21 · 2021: 18 · 2020: 9
- FWCI
- 12.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Reproduction (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (P20GM121298)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (L50 HD074152, K12HD000849)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- inflammaging, ovarian aging, macrophage ontogeny, macrophage polarization, M2 macrophages, monocyte recruitment, ovarian transcriptome, female fertility decline, oocyte quality, ovarian fibrosis, extracellular matrix
- MeSH terms
- Aging, Animals, Female, Gene Expression Regulation, Macrophages, Mice, Inbred C57BL, Ovary, Mice
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