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Vitamin D is an essential nutrient for regulating the levels of calcium and phosphate in the body, and for maintaining the health of bones, teeth, and muscles. Recent research has revealed new findings about the role of Vitamin D in anti-aging. As part of a balanced intake of vitamins, ensuring sufficient Vitamin D can be a key factor in healthy aging.
In February 2025, a Swiss research team published a study in the journal “Aging,” indicating that a combination of Omega-3, Vitamin D, and strength training can slow down the biological aging rate of the epigenetic clock in elderly individuals. This clinical trial involved 777 elderly participants and lasted for three years. Participants consumed 2000 International Units (IU) of Vitamin D daily, took one gram of Omega-3 daily, and engaged in a 30-minute home exercise program three times a week (either individually or in combination).
This is not the first time that Vitamin D has been found to have anti-aging effects. In 2024, a research paper published by Capital Medical University indicated that high levels of 25-(OH)D and physical exercise are associated with a reduced risk of biological aging. Moreover, the combination of high 25-(OH)D levels and physical exercise showed enhanced protective effects, particularly demonstrating a synergistic effect in middle-aged or young individuals. 25-(OH)D is the main circulating metabolite of Vitamin D in the human body and reflects the status of Vitamin D synthesis from the skin and dietary intake.
In 2024, the journal “Aging” published a research paper titled “The Anti-Aging Role of Vitamin D and Its Receptor in the Midgut of Drosophila.” Researchers used a well-established biological model of midgut stem cell aging in mature Drosophila and found that knocking down the Vitamin D receptor in intestinal cells induced intestinal stem cell proliferation, intestinal cell death, intestinal stem cell aging, and differentiation of intestinal endocrine cells. Additionally, Vitamin D treatment reduced the increase in intestinal stem cell proliferation and centromere amplification caused by aging and oxidative stress. These findings directly demonstrate the anti-aging effects of the Vitamin D/Vitamin D receptor pathway.
Vitamin D exerts its anti-aging effects through multiple pathways, including immune regulation, anti-inflammation, reduction of DNA oxidative damage, and improvement of mitochondrial dysfunction.
Research indicates that adequate levels of Vitamin D can reduce the risk of autoimmune diseases such as multiple sclerosis, demonstrating its significant immunomodulatory functions. Vitamin D is particularly important in enhancing the host’s first line of defense, especially during aging, as the elderly are at higher risk of infections. Most immune cells, including T cells, B cells, dendritic cells, macrophages, and monocytes, express the Vitamin D receptor (VDR) and respond to Vitamin D through fine-tuned regulation of cell signaling, pathway activation, and molecular production, thereby significantly impacting immune responses.
In 2024, the journal “Nutrients” published an article titled “Vitamin D and Aging: The Core Role in Immune Competence,” which pointed out that an individual’s specific response to Vitamin D is related to their immune competence. This is achieved through the epigenetic programming functions of VDR and its ligand calcitriol in both hematopoietic and peripheral systems. Therefore, individuals with sufficient Vitamin D levels have higher immune competence compared to those with Vitamin D deficiency.
In the same year, “Science Advances,” a sub-journal of “Science,” also published a study exploring the phenomena of abnormal epithelial cell differentiation and premature thymic aging in mice lacking Vitamin D signaling. This further substantiates the impact of Vitamin D on the immune system.
Inflammation is a universal mechanism evolved by organisms to protect themselves from infections and injuries. The inflammatory response triggered by acute infections or injuries can clear invading pathogens and promote wound healing. However, chronic inflammation is a potential pathological process. “Inflammaging” refers to a state of low-grade chronic inflammation that increases with age and affects multiple physiological processes. The occurrence of chronic inflammation is due to various disorders caused by aging characteristics and gradually increases based on the spatiotemporal interactions between intrinsic and extrinsic factors.
The immunomodulatory effects of Vitamin D are widely recognized to have a positive impact on healthspan and overall lifespan. Research shows that adequate levels of Vitamin D can counteract inflammation through multi-layered targeting mechanisms. Specifically, Vitamin D can inhibit the expression and signaling of TLR2, TLR4, and TLR9, reduce the production of cytokines such as TNF-α, IL-6, and IL-23, and suppress the activity of chemokines that recruit T cells. Therefore, Vitamin D plays a crucial role in regulating immune responses.
Additionally, chronic inflammation can disrupt the balance of the gut microbiota, and Vitamin D supplementation holds promise for restoring this microbial balance and reducing inflammation.
Vitamin D shows significant potential in regulating the integrity and stability of deoxyribonucleic acid (DNA), particularly in conditions such as type 2 diabetes and cancer. Research indicates that Vitamin D supplementation can reduce DNA damage and oxidative parameters, potentially offering protective effects against genomic instability and oncogene-induced aging. Epigenetic changes associated with diseases and aging are often related to DNA methylation. Vitamin D can regulate epigenetic aging by reducing methylation levels.
As aging progresses, significant changes occur in the structure and dynamics of mitochondria. In elderly individuals, mitochondria often become swollen, decrease in number, and do not replace themselves as rapidly as in younger individuals. Mitochondrial dysfunction is primarily caused by the accumulation of mitochondrial DNA mutations, increased generation of reactive oxygen species (ROS), and associated damage to cellular macromolecules. These changes lead to impaired cellular bioenergetics and increased mitochondrial membrane permeability, which in turn trigger inflammation, altered stress responses, and cell death. Various heart diseases, neurodegenerative diseases, muscle atrophy, and sarcopenia are associated with alterations in mitochondrial fission and fusion mechanisms.
Vitamin D also plays an important role in regulating mitochondrial function. Vitamin D deficiency is associated with mitochondrial dysfunction, such as respiratory chain dysregulation and delayed brain aging. Vitamin D can improve mitochondrial function through multiple direct and indirect pathways. Directly, Vitamin D can promote the repair of protein oxidation, lipid peroxidation, and DNA damage. Indirectly, Vitamin D regulates autophagy, inflammation, epigenetic modifications, DNA abnormalities, and changes in calcium and ROS signaling, thereby preventing mitochondrial dysfunction.
The interaction between Vitamin D and its receptor (VDR) plays a crucial role in delaying cellular aging, including the lengthening of telomeres. Telomeres are nucleotide sequences located at the ends of chromosomes that protect them and maintain genomic stability. As we age, telomerase activity is affected, leading to telomere shortening, which impairs cell function and lifespan. This is associated with various age-related diseases such as cardiovascular diseases, malignancies, dementia, osteoporosis, and frailty. Telomere attrition is influenced by both intrinsic and extrinsic factors such as diet and lifestyle, and there is evidence that Vitamin D has a protective effect.
Vitamin D is a steroid hormone essential for all vertebrates, including humans. It is also a fat-soluble vitamin naturally present in a few foods and added to others through fortification. Additionally, Vitamin D is widely used as a dietary supplement. The human body can synthesize Vitamin D through skin exposure to sunlight, where 7-dehydrocholesterol is converted to Vitamin D under ultraviolet radiation, which is the primary source of Vitamin D for humans. Its metabolic pathway is similar to that of cholesterol, beginning with acetyl-CoA in the cytoplasm. After processing in the liver, Vitamin D is converted to its active form, calcitriol. Calcitriol regulates calcium and phosphorus homeostasis in the body by binding to the Vitamin D receptor (VDR).
Despite our ability to produce Vitamin D through sunlight exposure, its presence in various natural and fortified foods, and its widespread availability as a dietary supplement, Vitamin D deficiency remains a significant public health issue. With the increasing proportion of the global elderly population, the efficiency of synthesizing Vitamin D through sun exposure decreases in older adults, increasing the risk of Vitamin D deficiency. Therefore, the elderly are more susceptible to Vitamin D deficiency, and supplementation is an effective option to promote healthy aging.
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