Elimination of senescent osteoclast progenitors has no effect on the age‐associated loss of bone mass in mice
Open accessAbstract
Both an increase in osteoclast and a decrease in osteoblast numbers contribute to skeletal aging. Markers of cellular senescence, including expression of the cyclin inhibitor p16, increase with aging in several bone cell populations. The elimination of p16-expressing cells in old mice, using the INK-ATTAC transgene, increases bone mass indicating that senescent cells contribute to skeletal aging. However, the identity of the senescent cells and the extent to which ablation of p16-expressing cells may prevent skeletal aging remain unknown. Using mice expressing the p16-3MR transgene, we examined whether elimination of p16-expressing cells between 12 and 24 months of age could preserve bone mass; and whether elimination of these cells from 20 to 26 months of age could restore bone mass. The activation of the p16-3MR transgene by ganciclovir (GCV) greatly diminished p16 levels in the brain, liver, and osteoclast progenitors from the bone marrow. The age-related increase in osteoclastogenic potential of myeloid cells was also abrogated by GCV. However, GCV did not alter p16 levels in osteocytes-the most abundant cell type in bone-and had no effect on the skeletal aging of p16-3MR mice. These findings indicate that the p16-3MR transgene does not eliminate senescent osteocytes but it does eliminate senescent osteoclast progenitors and senescent cells in other tissues, as described previously. Elimination of senescent osteoclast progenitors, in and of itself, has no effect on the age-related loss of bone mass. Hence, other senescent cell types, such as osteocytes, must be the seminal culprits.
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Whether osteoclasts undergo senescence remains unclear, although elimination of CDKN2A-expressing osteoclast progenitors did not attenuate age-related bone loss in mice.
“Whether osteoclasts also undergo senescence remains unclear, although elimination of CDKN2A-expressing osteoclast progenitors did not attenuate age-related bone loss in mice198.”
From SenNet recommendations for detecting senescent cells in different tissues (2024) · cites this paper as [198]
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- Authors
- Kim, H., Chang, J., Iyer, S., Han, L., Campisi, J., Manolagas, S. C., Zhou, D., & Almeida, M.
- Affiliations
- Central Arkansas Veterans Healthcare System (US)
- University of Arkansas for Medical Sciences (US)
- Buck Institute for Research on Aging (US)
- University of Florida Health (US)
- Corresponding author
- Almeida, Maria
- ORCID
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2019-02-17
- Volume
- 18
- Issue
- 3
- Pages
- e12923-e12923
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC6516158
- OpenAlex
- W2917303425
- Cited by
- 74
- References
- 13
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 13 · 2023: 15 · 2022: 13 · 2021: 16 · 2020: 6 · 2019: 2
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Aging Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 BX001405)
- National Institutes of Health (1UL1RR029884, P20GM125503, R01 AR56679, R01 CA122023, R01 CA211963 (DZ))
- Research and Development
- University of Arkansas
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- cellular senescence, osteoclast precursors, skeletal aging, bone loss, p16, ganciclovir, osteocytes, osteoclastogenesis
- MeSH terms
- Aging, Animals, Mice, Inbred C57BL, Mice, Transgenic, Osteoclasts, Stem Cells, Bone Density, Cellular Senescence, Mice
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