Targeting the Hallmarks of Aging with Vitamin D: Starting to Decode the Myth
Abstract
:1. Introduction
2. Methods
3. The Hallmarks of Aging
3.1. Genomic Instability
3.2. Telomere Attrition
3.3. Epigenetic Alterations
3.4. Loss of Proteostasis
3.5. Disabled Macroautophagy
3.6. Deregulated Nutrient-Sensing
3.7. Mitochondrial Dysfunction
3.8. Cellular Senescence
3.9. Stem Cell Exhaustion
3.10. Altered Intercellular Communication
3.11. Chronic Inflammation
3.12. Dysbiosis
4. Vitamin D and Its Potential Impact on the Biological Hallmarks of Aging
4.1. Vitamin D and Genomic Instability
4.2. Vitamin D and Telomere Attrition
4.3. Vitamin D and Epigenetic Alterations
4.4. Vitamin D and Lack of Proteostasis
4.5. Vitamin D and Mitochondrial Dysfunction
4.6. Vitamin D and Cellular Senescence
4.7. Vitamin D and Stem Cell Exhaustion
4.8. Vitamin D and Altered Intercellular Communication
4.9. Vitamin D and Chronic Inflammation
4.10. Vitamin D and Dysbiosis
Hallmark | Study | Cohort | Aim | Conclusion | Refs. |
---|---|---|---|---|---|
Genomic instability | Placebo-controlled | 92 patients with colorectal adenoma | Evaluate the effect of VitD supplement with 800 UI/day for 6 months | Significant increase in Bax expression (apoptosis promoter); no increase of Bcl-2 expression (apoptosis inhibitor) in VitD group | [61] |
Randomized Clinical Trial | 92 subjects with VitD insufficiency, with and without T2DM | Evaluate the effect of VitD supplement with 2000 UI/day for 3 months | Decreased percentage of DNA damage and oxidative parameters when compared to the control group | [62] | |
Telomere Attrition | Twins UK Cohort ObservationalRegistry | 2160 women (aged 18–79) from population-based cohort of twins | Evaluate the relationship between VitD concentrations and the rate of telomere attrition in leukocytes | Positive correlation between serum 25(OH)D levels and telomere length | [64] |
Nurses’ Health Study Observational Registry | 1424 women | Evaluate the association between both 25(OH)D and 1,25(OH)2D and leukocyte telomere length | Positive correlation between serum 25(OH)D concentrations and leukocyte telomere length | [65] | |
Cross sectional analysis from the Health Professional Follow-Up study | 2843 men (from studies of telomeres and cancer) | Evaluate the association between 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)2D) and leukocyte telomere length | No association between VitD levels and leukocyte telomere length | [66] | |
Cross sectional analysis from Northern Finland Birth Cohort 1966 | 5096 younger adults | Evaluate associations between 25(OH)D and body mass index (BMI) with leukocyte telomere length and whether associations are independent of concentrations of C-reactive protein | No association between VitD levels and leukocyte telomere length | [67] | |
Cohort from the Newcastle 85+ Study | 775 older adults (>85 ys), community dwelling, and institutionalized older patients | Evaluate the association between serum VitD concentration and telomere length in blood cells at baseline, 18 and 36 months | Significant positive association between VitD and telomere length at baseline, but inconsistent relationships at subsequent time points | [68] | |
Case–control study | African American Gullah women with systemic lupus erythematosus (n = 59) and healthy controls (n = 59) | Evaluate the relationships between VitD status, telomere length, and anti-telomere antibodies | Significant association between shorter telomeres and lower 25(OH)D levels in patients and healthy control; shorter telomeres at follow-up in VitD-deficient patients | [69] | |
Retrospective case–control study | 62 stable hemodialysis patients and 60 controls | Evaluate the potential protective role of VitD supplementation on telomere length in peripheral mononuclear cells | Hemodialysis patients treated with VitD had greater telomere length in peripheral mononuclear cells | [70] | |
Double-blind, placebo-controlled clinical trial | 37 overweight African American subjects (18 placebo and 19 intervention) | Evaluate the effect of VitD3 oral supplementation (60,000 IU/month) | VitD supplementation significantly increased telomerase activity | [74] | |
Epigenetic alteration | Sub analysis from RCT | 51overweight/obese African Americans VitD-deficient subjects | Evaluate different effects of VitD3 supplement (600 IU/day, 2000 IU/day, and 4000 IU/day) for 16 weeks compared to placebo | DNAm age was correlated with chronological age in patients with low VitD levels, while the supplementation was able to decrease DNA metilation and slowed epigenetic aging | [75] |
Southampton Women’s Survey: subgroup analysis from prospective cohort | 230 children from the Southampton Women’s Survey (SWS) mother–offspring study | Evaluate the correlation between VitD status and Retinoid-X receptor-alpha (RXRA) methylation in umbilical cord DNA | Methylation at RXRA locus in the umbilical cord was associated with the offspring bone mass; specific methylation at one locus was associated with maternal VitD deficiency | [78] | |
The Maternal VitD Osteoporosis Study (MAVIDOS RCT): subgroup analysis | 479 received VitD3 supplementation and 486 were in the placebo group | Evaluate DNAm at a specific site in the RXRA locus (10 CpG) | In the cohort of mothers’ receiving VitD, the methylation levels in the RXRA-specific site were significantly lower compared to the placebo group | [79] | |
Randomized controlled pilot study | Pregnant women receiving VitD3 400 IU (n = 6, control group) or 3800 IU (n = 7, intervention group) | Identify differentially methylated loci among infants born to mothers supplemented with VitD 400 IU/day (i.e., control) versus 3800 IU/day (i.e., intervention) | Compared to control, intervention was associated with mean 25(OH)D levels reflective of sufficient maternal VitD status by birth, as well as significant gains in maternal leukocyte DNA methylation associated with genes involved in cell migration/motility, development, and growth | [80] | |
Cellular senescence | Case–control study | 120 individuals (30 young, 30 older, and 30 older in treatment group 1 (1 sachet of Difensil® IMMUNO/day for 12 weeks) and 20 older in treatment group 2 (2 sachet of Difensil® IMMUNO/day for 6 weeks) | Evaluate the effect of the nutraceutical supplement (comprehensive of Sambucus nigra, zinc, tyndallized Lactobacillus acidophilus (HA122), arabinogalactans, VitD, vitamin E, vitamin C, and group B vitamins) on specific signatures of immunosenescence | Older people treated for 30 days improved IL-6, CRP, and lymphocytes levels independent from the dosage of the supplements used; despite the improvement, they were not able to reach the same conditions of young patients | [95] |
Double Blind RCT | 110 older fit or frail subjects | Evaluate the effect of alphacalcidol supplementation in inflammatory profile (Il-6, IL-10, TNF, CD4/CD8 ratio, CD8+, and CD28-) | Cohort receiving alphacalcidiol had a better immune profile across the whole cohort as well as the cohort divided according to frailty status | [96] | |
Chronic inflammation | VITAL study sub-cohort | 25,871 women aged ≥55 and men aged ≥50 | Measure the effect of VitD supplementation (2000 UI/day) and/or n-3 FAs on systemic inflammatory biomarkers | VitD supplementation with or without n-3 FAs decreased hs-CRP by 19% at year 2, and the reduction was attenuated at 4 years Other inflammatory biomarkers (IL-6, IL-10, and TNF-α) were not significantly modified | [114] |
Dysbiosis | Sub analysis from a RCT | 167 HIV-1 patients receiving VitD 5000 IU/day and 500 mg phenylbutyrate (PBA) for 16 weeks | VitD or PBA may have a modulatory action on microbiota composition, metabolites production, and immune activation | No significant improvement in circulating antimicrobial peptide LL-37 and an actual impact on microbiota | [115] |
Pilot study | 24 patients with knee osteoarthritis (KOA), healthy controls, with and without VitD deficiency | Evaluate the interplay between microbiome, knee OA (KOA), and VitD levels for establishing whether VitD deficiency is associated with microbiome dysfunction | Patients with KOA and VitD-deficient showed specific bacteria species, absent in KOA, and not VitD-deficient; The different core bacteria in KOA and VitD-deficient suggested an interplay between conditions | [116] | |
RCT | 41 patients with cystic fibrosis divided in VitD insufficient (n = 23) and VitD sufficient (n = 18) | Comparing microbiota composition in VitD insufficient and sufficient patients and evaluate the impact of VitD supplement. | Potentially pathogenic species were identified in the microbiome of VitD-deficient subjects | [117] | |
Interventional study | 100 healthy women | Evaluate gut microbiota composition before and after VitD supplementation | Significant increment of health-promoting gut probiotics after VitD supplementation | [118] |
5. Discussion and Future Perspectives
Funding
Conflicts of Interest
References
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Ruggiero, C.; Tafaro, L.; Cianferotti, L.; Tramontana, F.; Macchione, I.G.; Caffarelli, C.; Virdis, A.; Ferracci, M.; Rinonapoli, G.; Mecocci, P.; et al. Targeting the Hallmarks of Aging with Vitamin D: Starting to Decode the Myth. Nutrients 2024, 16, 906. https://doi.org/10.3390/nu16060906
Ruggiero C, Tafaro L, Cianferotti L, Tramontana F, Macchione IG, Caffarelli C, Virdis A, Ferracci M, Rinonapoli G, Mecocci P, et al. Targeting the Hallmarks of Aging with Vitamin D: Starting to Decode the Myth. Nutrients. 2024; 16(6):906. https://doi.org/10.3390/nu16060906
Chicago/Turabian StyleRuggiero, Carmelinda, Laura Tafaro, Luisella Cianferotti, Flavia Tramontana, Ilaria Giovanna Macchione, Carla Caffarelli, Agostino Virdis, Marika Ferracci, Giuseppe Rinonapoli, Patrizia Mecocci, and et al. 2024. "Targeting the Hallmarks of Aging with Vitamin D: Starting to Decode the Myth" Nutrients 16, no. 6: 906. https://doi.org/10.3390/nu16060906