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Senescence of bone marrow mesenchymal stem cells in Wistar male rats receiving normal chow/high-calorie diets with/without vitamin D

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Abstract

Bone marrow mesenchymal stem cells (BM-MSCs) have a momentous function in the composition of the bone marrow microenvironment because of their many valuable properties and abilities, such as immunomodulation and hematopoiesis. The features and actions of MSCs are influenced by senescence, which may be affected by various factors such as nutritional/micronutrients status, e.g., vitamin D. This study aimed to examine the effects of a high-calorie diet (HCD) with/without vitamin D on BM-MSCs senescence. In the first phase, 48 middle-aged rats were fed a normal chow diet (NCD, n = 24) and an HCD (n = 24) for 26 weeks. Afterward, the rats in each group were randomly divided into three equal subgroups. Immediately, eight-rat from each diet group were sacrificed to assess the HCD effects on the first phase measurements. In the second phase, the remaining 4 groups of rats were fed either NCD or HCD with (6 IU/g) or without vitamin D (standard intake: 1 IU/g); in other words, in this phase, the animals were fed (a) NCD, (b) NCD plus vitamin D, (c) HCD, and (d) HCD plus vitamin D for 4 months. BM-MSCs were isolated and evaluated for P16INK4a, P38 MAPK, and Bmi-1 gene expression, reactive oxygen species (ROS) levels, SA-β-gal activity, and cell cycle profile at the end of both phases. After 26 weeks (first phase), the ROS level, SA-β-gal-positive cells, and cells in the G1 phase were significantly higher in HCD-fed rats than in NCD-fed ones (P < 0.05). HCD prescription did not significantly affect cells in the S and G2 phases (p > 0.05). Compared with the NCD-fed animals, P16INK4a and P38 MAPK gene expression were up-regulated in the HCD-fed animals; also, Bmi-1 gene expression was down-regulated (P < 0.05). BM-MSCs from vitamin D-treated rats (second phase) exhibited reduced mRNA levels of P16INK4a and P38 MAPK genes and increased Bmi-1 mRNA levels (all P < 0.05). Vitamin D prescription also declined the percentage of SA-β-gal-positive cells, ROS levels, and the cells in the G1 phase and increased the cells in the S phase in both NCD and HCD-fed animals (P < 0.05). The reduction of the cells in the G2 phase in rats fed with an NCD plus vitamin D was statistically non-significant (P = 0.128) and significant in HCD plus vitamin D rats (P = 0.002). HCD accelerates BM-MSCs senescence, and vitamin D reduces BM-MSCs senescence biomarkers.

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Funding

The Iran University of Medical Sciences funded the study.

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Authors and Affiliations

  1. Saveh University of Medical Sciences, Saveh, Iran

    Fahimeh Agh

  2. Student Research Committee, Saveh University of Medical Sciences, Saveh, Iran

    Fahimeh Agh

  3. Department of Hematology, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran

    Seyed Hadi Mousavi

  4. Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran

    Naheed Aryaeian & Fatemehsadat Amiri

  5. Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran

    Mohammad Reza Jalilvand

  6. Department of Nutrition, School of Public Health, Golestan University of Medical Sciences, Gorgan, Iran

    Motahareh Hasani

  7. Nutrition and Health Research Group, Department of Precision Health, Luxembourg Institute of Health, Strassen, Luxembourg

    Farhad Vahid

  8. Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Fatemeh Sepahvand

  9. Iran University of Medical Sciences, Tehran, Iran

    Mehran Vosugh

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  1. Fahimeh Agh
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  2. Seyed Hadi Mousavi
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Contributions

FA, NA, SHM and MRJ were contributed in the research idea and final drafting of the study , FA and MH, FS, and MV were participated in experimenting. FA and FV took part in the writing.

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Correspondence to Seyed Hadi Mousavi or Naheed Aryaeian.

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Agh, F., Mousavi, S.H., Aryaeian, N. et al. Senescence of bone marrow mesenchymal stem cells in Wistar male rats receiving normal chow/high-calorie diets with/without vitamin D. Biogerontology 24, 801–812 (2023). https://doi.org/10.1007/s10522-023-10048-9

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