Estrogen, not intrinsic aging, is the major regulator of delayed human wound healing in the elderly
Open accessAbstract
Background: Multiple processes have been implicated in age-related delayed healing, including altered gene expression, intrinsic cellular changes, and changes in extracellular milieu (including hormones). To date, little attempt has been made to assess the relative contribution of each of these processes to a human aging phenomenon. The objective of this study is to determine the contribution of estrogen versus aging in age-associated delayed human wound healing. Results: Using an Affymetrix microarray-based approach we show that the differences in gene expression between male elderly and young human wounds are almost exclusively estrogen regulated. Expression of 78 probe sets was significantly decreased and 10 probe sets increased in wounds from elderly subjects (with a fold change greater than 7). A total of 83% of down-regulated probe sets and 80% of up-regulated probe sets were estrogen-regulated. Differentially regulated genes were validated at the level of gene and protein expression, with genes identified as estrogen-regulated in human confirmed as estrogen-dependent in young estrogen depleted mice in vivo. Moreover, direct estrogen regulation is demonstrated for three array-identified genes, Sele, Lypd3 and Arg1, in mouse cells in vitro. Conclusion: These findings have clear implications for our understanding of age-associated cellular changes in the context of wound healing, the latter acting as a paradigm for other age-related repair and maintenance processes, and suggest estrogen has a more profound influence on aging than previously thought.
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Hormones, particularly estrogens and androgens, are contributing factors in aging and have been implicated as regulators of wound healing in experimental models and patients.
“Hormones, particularly estrogens and androgens, are contributing factors in aging and have been implicated as regulators of wound healing in experimental models and patients (112, 163, 172, 173).”
From Wound repair and regeneration: Mechanisms, signaling, and translation (2014) · cites this paper as [172]
In a gene expression profiling study of wound tissues from young and elder men, 78% of differentially expressed genes were estrogen-regulated and only 3% were age-related.
“One gene expression profiling study of wound tissues from young and elder men found that among genes that were differentially expressed, 78% of them being estrogen-regulated and only 3% being age-related34”
From Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells (2020) · cites this paper as [34]
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- Authors
- Hardman, M. J., & Ashcroft, G. S.
- Affiliations
- University of Manchester (GB)
- Corresponding author
- Hardman, Matthew J
- Ashcroft, Gillian S
- ORCID
- Hardman, Matthew J
- Venue
- Genome Biology
- Published
- 2008-05-13
- Volume
- 9
- Issue
- 5
- Pages
- R80-R80
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC2441466
- OpenAlex
- W2145350152
- Cited by
- 157
- References
- 35
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 10 · 2023: 10 · 2022: 18 · 2021: 5 · 2020: 10 · 2019: 7 · 2018: 12 · 2017: 12 · 2016: 6 · 2015: 8 · 2014: 10 · 2013: 6 · 2012: 5
- FWCI
- 7.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Funders
- Wellcome Trust
- University of Manchester
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- estrogen, wound healing, aging, older adults, gene expression, estrogen-regulated genes, SELE, Arg1, estrogen deficiency, tissue repair
- MeSH terms
- Aged, Aging, Animals, Estrogens, Gene Expression Regulation, Humans, Male, Wound Healing, Down-Regulation, Up-Regulation, Oligonucleotide Array Sequence Analysis, Mice
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