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

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.

From the Sun to the Cell: Examining Obesity through the Lens of Vitamin D and Inflammation

“…During the ageing process, damage from various agents accumulates in cells, which triggers senescence, leading to the loss of the cells’ ability to divide and exhibit specific characteristics [ 10 ]. Cellular senescence occurs due to various factors: DNA damage, telomere shortening, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, mitotic stress, oxidative stress, and oncogene activation [ 11 , 12 , 13 ].…”

“…This includes elevated senescence-associated β-galactosidase (SA β-gal) activity, an upregulated expression of cyclin-dependent kinase inhibitor-1 A (CDKNlA) and p53, and an increased production of proinflammatory cytokines and chemokines [ 22 , 23 ]. SASP includes inflammatory and profibrotic factors, which can induce secondary senescence in adjacent cells in a manner modulated by transcription factors, such as NF-κB and C/EBP (CCAAT/enhancer-binding protein) [ 10 ]. SA β-gal activity increases in AT as the body mass index (BMI) increases [ 24 ].…”

“…Recent research has revealed that vitamin D regulates the expression of genes associated with the immune system, thereby exerting anti-inflammatory effects. The ability of immune cells (macrophages, B and T cells, and dendritic cells) to produce and express vitamin D receptor (VDR) provides support for this hypothesis [ 10 ].…”

“…The primary target genes include transcription factors whose expression is directly influenced by activated VDR following 1,25(OH) 2 D 3 binding. These primary target genes subsequently downregulate the expression of secondary target genes, allowing vitamin D to exert anti-inflammatory effects [ 10 ]. Both adipocytes and immune cells express the VDR gene and enzymes associated with the effect of vitamin D. This highlights the critical role of vitamin D in ensuring the proper functioning of AT.…”

Targeting the Hallmarks of Aging with Vitamin D: Starting to Decode the Myth

“…Proinflammatory cytokines released by the secretome may increase and trigger secondary senescence in the surrounding environment. Again, VitD supplementation seems to be related to decreased cellular senescence and SASP [ 93 ]. Part of the aging process is related to the aging of the immune system due to thymic involution and function and the increased number of T immature T lymphocytes, with the immune phenotype changing towards a lower CD4/CD8 ratio and a decreasing amount of T CD8+CD28+ cells.…”