Journal article
Regulation of stem cell aging and cellular proliferation by Klotho-Sirt1 pathways in heart, kidney and small intestine
npj aging, Vol.11(1), 93
11/25/2025
DOI: 10.1038/s41514-025-00286-1
PMCID: PMC12647711
PMID: 41290698
Abstract
We investigate the effects of α-Klotho, an anti-aging hormone, on cell proliferation across three tissues with varying regenerative capacities in the context of aging. Using young and old wild-type mice, alongside old heterozygous Klotho-deficient mice, we administered soluble α-Klotho (sKL) daily for 10 weeks to elucidate the impact of α-Klotho deficiency and its supplementation. Our investigation spanned three organs: the small intestine, the kidney, and the heart. We measured cell cycle markers (BrdU, Ki-67, and phospho-histone-3), Sirtuin-1, DNA-damage response pathways (gamma-H2Ax, ATM, CHK2), and the aging phenotypes. Supplementation of sKL significantly enhances proliferative markers and attenuates many aging changes. Mechanistic studies show that sKL acts through the Sirt1-CHK2 pathway to promote cell proliferation. In summary, Klotho deficiency exacerbated aging phenotypes, reduced regenerative capacity, and impaired cellular proliferation. Supplementation with sKL effectively counters these age-related declines across multiple tissues by enhancing cellular proliferation and attenuating aging phenotypes through the Sirt1-CHK2 signaling pathway.
Details
- Title: Subtitle
- Regulation of stem cell aging and cellular proliferation by Klotho-Sirt1 pathways in heart, kidney and small intestine
- Creators
- Dao-Fu Dai - Johns Hopkins University School of MedicineNastaran Daneshgar - University of IowaKaihao Wang - Johns Hopkins University School of MedicinePei-Ing Liang - Kaohsiung Medical University Chung-Ho Memorial HospitalDustin Bosch - University of IowaChad Grueter - University of Iowa
- Resource Type
- Journal article
- Publication Details
- npj aging, Vol.11(1), 93
- DOI
- 10.1038/s41514-025-00286-1
- PMID
- 41290698
- PMCID
- PMC12647711
- NLM abbreviation
- NPJ Aging
- ISSN
- 2731-6068
- eISSN
- 2731-6068
- Publisher
- Springer Nature
- Grant note
- HL145138, DK133118 / NIH HHS K08 HL145138 / NHLBI NIH HHS R01 DK133118 / NIDDK NIH HHS
- Language
- English
- Date published
- 11/25/2025
- Academic Unit
- Pathology; Cardiovascular Medicine; Craniofacial Anomalies Research Center; Internal Medicine
- Record Identifier
- 9985034931502771
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