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Review
. 2023 Mar 10;15(6):1349.
doi: 10.3390/nu15061349.

Vitamin D, Cellular Senescence and Chronic Kidney Diseases: What Is Missing in the Equation?

Romina P Martinelli  1 , Sandra Rayego-Mateos  1   2 , Matilde Alique  2   3   4 , Laura Márquez-Expósito  1   2 , Lucia Tejedor-Santamaria  1   2 , Alberto Ortiz  2   5 , Emilio González-Parra  2   5 , Marta Ruiz-Ortega  1   2
Affiliations
Review

Vitamin D, Cellular Senescence and Chronic Kidney Diseases: What Is Missing in the Equation?

Romina P Martinelli et al. Nutrients. .

Abstract

As life expectancy increases in many countries, the prevalence of age-related diseases also rises. Among these conditions, chronic kidney disease is predicted to become the second cause of death in some countries before the end of the century. An important problem with kidney diseases is the lack of biomarkers to detect early damage or to predict the progression to renal failure. In addition, current treatments only retard kidney disease progression, and better tools are needed. Preclinical research has shown the involvement of the activation of cellular senescence-related mechanisms in natural aging and kidney injury. Intensive research is searching for novel treatments for kidney diseases as well as for anti-aging therapies. In this sense, many experimental shreds of evidence support that treatment with vitamin D or its analogs can exert pleiotropic protective effects in kidney injury. Moreover, vitamin D deficiency has been described in patients with kidney diseases. Here, we review recent evidence about the relationship between vitamin D and kidney diseases, explaining the underlying mechanisms of the effect of vitamin D actions, with particular attention to the modulation of cellular senescence mechanisms.

Keywords: biological aging; cellular senescence; chronic kidney diseases; premature aging; vitamin D.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Pleiotropic actions of vitamin D related to cellular senescence. 1,25D counteracts the effects of progerin on DNA stability, helps to regulate epigenetic age, maintains protein homeostasis, preserves telomere length, regulates gene transcription and reduces oxidative stress by regulating pro-oxidant and antioxidant genes.
Figure 2
Figure 2
Vitamin D and T cells. 1,25(OH)2VD3 leads to an increase in the expression of PLC-γ1 and TGF-β1, ultimately resulting in the induction of FOXP3 expression and differentiation of naive T cells into regulatory T cells (Treg).
Figure 3
Figure 3
Vitamin D and the kidney. In response to injury, mitochondrial dysfunction in tubular epithelial cells diminishes 1,25D due to lower activation. Additionally, vitamin D deficiency contributes to kidney damage progression.
Figure 4
Figure 4
Vitamin D and cellular senescence in the kidney. Proposed mechanisms in response to injury; mitochondrial dysfunction in tubular epithelial cells diminishes 1,25D due to lower activation. Additionally, vitamin D deficiency contributes to kidney damage progression.
See this image and copyright information in PMC

References

    1. Ortiz A., Asociación Información Enfermedades Renales Genéticas (AIRG-E) European Kidney Patients’ Federation (EKPF) Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón (ALCER) Fundación Renal Íñigo Álvarez de Toledo (FRIAT) Red de Investigación Renal (REDINREN) Resultados en Salud 2040 (RICORS2040) Sociedad Española de Nefrología (SENEFRO) Council. Sociedad Española de Trasplante (SET) Council. Organización Nacional de Trasplantes (ONT) RICORS2040: The need for collaborative research in chronic kidney disease. Clin. Kidney J. 2021;15:372–387. doi: 10.1093/ckj/sfab170. - DOI - PMC - PubMed
    1. Rayego-Mateos S., Marquez-Expósito L., Rodrigues-Diez R., Sanz A.B., Guiteras R., Doladé N., Rubio-Soto I., Manonelles A., Codina S., Ortiz A., et al. Molecular Mechanisms of Kidney Injury and Repair. Int. J. Mol. Sci. 2022;23:1542. doi: 10.3390/ijms23031542. - DOI - PMC - PubMed
    1. Ruiz-Ortega M., Rayego-Mateos S., Lamas S., Ortiz A., Rodrigues-Diez R.R. Targeting the progression of chronic kidney disease. Nat. Rev. Nephrol. 2020;16:269–288. doi: 10.1038/s41581-019-0248-y. - DOI - PubMed
    1. Rayego-Mateos S., Rodrigues-Diez R.R., Fernandez-Fernandez B., Mora-Fernández C., Marchant V., Donate-Correa J., Navarro-González J.F., Ortiz A., Ruiz-Ortega M. Targeting inflammation to treat diabetic kidney disease: The road to 2030. Kidney Int. 2022;103:282–296. doi: 10.1016/j.kint.2022.10.030. - DOI - PubMed
    1. Ruiz-Ortega M., Lamas S., Ortiz A. Antifibrotic Agents for the Management of CKD: A Review. Am. J. Kidney Dis. 2022;80:251–263. doi: 10.1053/j.ajkd.2021.11.010. - DOI - PubMed