Abstract
Our previous studies found that deletion of nuclear receptor interacting protein 1 (Nrip1) extended longevity in female mice and delayed cell senescence. The current study investigates the role of NRIP1 in regulating functions of adipose-derived mesenchymal stem cells (ADMSCs) and explores the mechanisms of NRIP1 in skin aging. We first verified the skin aging phenotypes in young (6 months) and old (20 months) C57BL/6J (B6) mice and found deletion of Nrip1 can delay skin aging phenotypes, including reduced thickness of dermis and subcutaneous white adipose tissue (sWAT), as well as the accumulation of senescent cells in sWAT. In ADMSCs isolated from sWAT, we found that deletion of Nrip1 could decrease cell proliferation, prevent cell apoptosis, and suppress adipogenesis. Interestingly, deletion of Nrip1 also reduced cell senescence and maintain cell quiescence of ADMSCs. Moreover, the expressions of genes associated with senescence (p21, and p53), inflammation (p65, IL6, and IL1a), and growth factor (mTOR, Igf1) were reduced in Nrip1 knockout ADMSCs, as well as in siNrip1-treated ADMSCs. Suppression of Nrip1 by siNrip1 also decreased the expressions of mTOR, p-mTOR, p65, and p-p65 in ADMSCs. Reduced expressions of p65 and p-p65 were also confirmed in the skin of Nrip1 knockout mice. These findings suggest that NRIP1 plays an important role in delaying skin aging by reducing ADMSCs senescence and maintaining ADMSCs quiescence.
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Lisa Hensley kindly edited the manuscript. Division of Laboratory Animal Medicine of Southern Illinois University School of Medicine provides excellent environment for animal research.
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The work is funded by U.S. NIH grant AG046432, internal research seed grants of Southern Illinois University School of Medicine, team science grant of simmons cancer institute at Southern Illinois University School of Medicine, CAMS Innovation Fund for Medical Sciences (CIFMS-2017-I2M-1-017), and China Scholarship Council (No. 201806210434).
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RY conceived and designed the project; YH, YZ, SDG, and JMO performed the experiments; RY, YH, YZ, and SDG analyzed experimental results; YH and RY wrote the manuscript with approval from all authors; RY, HG, and MC revised the manuscript.
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Hu, Y., Zhu, Y., Gerber, S.D. et al. Deletion of Nrip1 delays skin aging by reducing adipose-derived mesenchymal stem cells (ADMSCs) senescence, and maintaining ADMSCs quiescence. GeroScience 43, 1815–1833 (2021). https://doi.org/10.1007/s11357-021-00344-y
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DOI: https://doi.org/10.1007/s11357-021-00344-y