Vitamin D shows promise in targeting aging’s biological mechanisms, study finds

In a recent review article published in Nutrients, researchers summarized what is currently known about the potential effect of vitamin D (VitD) on modulating some hallmarks of aging and age-related diseases.

Overall, a small body of evidence indicates that VitD has some pleiotropic properties that may modify aging processes, but further investigation is needed to draw clinical conclusions and develop therapies.

Study: Targeting the Hallmarks of Aging with Vitamin D: Starting to Decode the Myth. Image Credit: FotoHelin/Shutterstock.com

The process of aging

Aging is marked by gradual and progressive declines in the functioning of organs and is associated with a greater probability of developing age-related illnesses and dying. Age-related changes are inextricably linked with specific pathways or ‘hallmarks.’

In the case of mammals, these are dysbiosis, chronic inflammation, intercellular communication alternations, exhaustion of stem cells, cellular senescence, mitochondrial dysfunction, nutrient sensing deregulation, disabled macroautophagy, proteostasis loss, epigenetic alterations, telomere attrition, and genomic instability.

These hallmarks show complex interrelationships and act synergistically or individually to trigger cellular and molecular damage through integrative, primary, or antagonistic mechanisms.

Cumulatively, these damages have universally adverse effects. However, understanding the relationships between and among these hallmarks could lead to the identification of interventions that modulate these mechanisms, thereby preventing or reducing age-related diseases.

The contribution of VitD

VitD is a vital fat-soluble hormone synthesized through ultraviolet irradiation of 7-dehydrocholesterol. It follows a metabolic pathway akin to cholesterol, starting with acetyl coenzyme A in the cytosol.

After liver processing, it converts into calcitriol, the active form. Calcitriol regulates calcium and phosphorus homeostasis by binding to the VitD receptor (VDR). Beyond bone health, VitD has immunomodulatory functions and affects mitochondrial bioenergetics.

Variations in the VDR gene have been studied for their impact on VitD function, potentially influencing physiological processes.

Though research on VitD’s impact on aging is limited, its genomic actions via VDRs and cytoplasmic membrane receptors suggest diverse cellular effects.

VitD and hallmarks of aging

VitD shows potential in modulating deoxyribonucleic acid (DNA) integrity and stability, particularly in conditions like type 2 diabetes mellitus (T2DM) and cancer.

Studies suggest VitD supplementation may reduce DNA damage and oxidative parameters, potentially offering protective effects against genomic instability and oncogene-induced senescence.

Epigenetic alterations linked to diseases and aging correlate with DNA methylation (DNAm). VitD may modulate epigenetic aging, reducing methylation levels.

In pregnant women, VitD supplementation is associated with lower retinoid-X-receptor-alpha (RXRA) methylation, impacting offspring bone mass and infant developmental processes.

Cellular senescence, a hallmark of aging, involves reduced proliferative capacity and a pro-inflammatory secretory phenotype (SASP). VitD supplementation shows promise in reducing senescence and inflammation.

Trials with nutraceutical supplements and alphacalcidol demonstrate improved immune profiles in older adults, underscoring VitD’s immunomodulatory role in aging and chronic inflammation.

VitD regulates protein homeostasis, impacting longevity and muscle health. In C. elegans, VitD reduces protein insolubility and toxicity, promoting longevity. In rats, VitD deficiency increases muscle protein breakdown and contributes to muscle atrophy.

VitD also influences cellular signaling involved in myogenesis and activates adenosine monophosphate-activated protein kinase (AMPK) during metabolic stress.

VitD impacts cellular and mitochondrial function across various systems. It reduces oxidative stress, improves muscle and lung function, and attenuates oxidative damage in neurodegenerative and cardiovascular diseases.

VitD also shows potential in mitigating mitochondrial dysfunction in conditions like sarcopenia and Crohn’s disease.

VitD also plays a crucial role in regulating immune responses by its widespread distribution among immune cells and autonomic control of active VitD concentration at inflamed sites.

While some studies link VitD supplementation to reduced inflammation markers in various conditions, overall evidence is inconclusive despite potential benefits in certain diseases.

Chronic inflammation can disrupt gut microbiota balance, as seen in conditions like human immunodeficiency virus (HIV) infection and osteoarthritis (OA). VitD supplementation shows promise in restoring microbial balance and reducing inflammation.

Studies indicate VitD’s role in enhancing antimicrobial peptides, stabilizing gut barriers, and regulating microbiota composition.

VitD shows potential in bone regeneration and neural stem cell modulation, crucial for nervous system development and repair. It influences signaling in brain neurogenesis and may have therapeutic implications in conditions like acute myeloid leukemia. However, further research is needed to explore its full potential in stem cell therapy.

Research on VitD’s role in intercellular communication, particularly in bone cells, is limited. Studies suggest VitD might affect gene expression in osteoclast formation and influence receptor expression in osteoblast-like cells. Further research is needed to explore its impact fully.

VitD shows varied associations with telomere length in different populations. While some studies suggest a positive correlation between VitD levels and telomere length, Mendelian randomization studies do not support a causal relationship. However, VitD supplementation may enhance telomerase activity, potentially benefiting telomere wellness.

Conclusions

Understanding aging involves complex interactions among various biological mechanisms. VitD shows promise in influencing the hallmarks of aging, including genomic stability and senescence.

However, further research is needed to fully comprehend its impact and potential clinical applications in promoting healthy aging.