In the large population of women in the present study, higher serum 25-hydroxyvitamin D concentrations were associated with longer LTL. Moreover, in every tertile of vitamin D, LTL was shorter in individuals with higher CRP concentrations. The difference in multiply adjusted LTL between the highest and lowest serum vitamin D tertiles was similar in magnitude to the difference in LTL associated with 5 y of chronologic age. Although these associations do not prove causality, they do suggest that vitamin D may play an important role in the modulation of LTL, which is related to aging and age-related diseases. Previous studies indicated that shortened LTL is an independent risk factor for coronary heart disease (37
), and our results suggest that vitamin D, which is easily modifiable through supplementation, may possibly attenuate LTL degradation.
Vitamin D supplement users were also found to have longer LTLs than did nonusers, which provides support for this hypothesis. The reduction in total sample size by 1460 subjects in this subset analysis of vitamin supplement use possibly explains why this difference was only of borderline significance. However, direct measurement of serum 25-hydroxyvitamin D concentrations is likely a better proxy for vitamin D status that is the use of supplements alone.
There are several mechanisms that may explain the association between LTL and vitamin D concentrations. Vitamin D decreases the mediators of systemic inflammation, such as interleukin-2 and tumor necrosis factor-α
), and, confirming this, in our study population, vitamin D concentrations were negatively correlated with levels of CRP. Vitamin D receptors are ubiquitously expressed in T and B lymphocytes, natural killer cells, and monocytes (49
), and through the down-regulation of cytokines and other proinflammatory factors, vitamin D exerts profound antiinflammatory and antiproliferative actions, which would affect the turnover rate of leukocytes (1
). It follows that vitamin D would attenuate the rate of LTL attrition.
Inflammation and oxidative stress are key determinants in the biology of aging (51
), and LTL dynamics appear to chronicle the accruing burden of these variables (52
). The present study further supports the concept that LTL may serve as a cumulative index of an individual’s lifelong burden of oxidative stress and inflammation (52
). Some of the factors that heighten oxidative stress and inflammation are genetic, but others are clearly environmental in nature, and a few may be easily modifiable. For instance, cigarette smoking (34
), obesity (34
), and sedentary lifestyle (44
) are associated with shortened LTL. Whereas these lifestyle habits may be difficult to change, vitamin D concentrations are easily modifiable through nutritional supplementation or sunshine exposure.
We note the limitation of the cross-sectional approach of studying LTL, which may represent cumulative lifetime exposure to oxidative stress and inflammatory burden. In contrast, serum vitamin D concentrations represent the status of the vitamin at a certain time point. Therefore, longitudinal studies with multiple time points would provide a much more coherent account of the effect of different variables, including vitamin D, on leukocyte telomere dynamics. For example, longitudinal studies indicate that insulin resistance explains 28% (53
) of the variation in leukocyte telomere attrition, whereas cross-sectional studies of this relation show that insulin resistance explains only 2.5% of the variation in LTL (27
). The reason for this is that LTL is highly variable at birth (54
) and is as variable afterward. Thus, cross-sectional studies of LTL may not always capture reliably the effect of a given factor on LTL attrition rate. On the basis of these considerations, our findings suggest that the effect of vitamin D on leukocyte telomere attrition may not be at all trivial.
We also note that the observations afforded by twin pairs in our cohort are not necessarily independent, and we have thus controlled for nonindependence by using robust statistical methods. Furthermore, our twin cohort was shown to be similar to the general population of the United Kingdom (41
). Finally, our results are cross-sectional and therefore may only suggest causality.
In conclusion, our study provides evidence that a longer LTL is associated with increased serum vitamin D concentrations in women. Although both LTL and serum vitamin D concentrations decrease with age and are thus possible markers of aging in general, we have shown that the positive association between LTL and vitamin D concentrations is independent of age and many other covariates. Vitamin D exerts immunomodulatory effects that may attenuate LTL attrition rate. Longitudinal studies or randomized controlled trials of supplementation exploring the effect of vitamin D on LTL will be necessary to unequivocally establish the relation between vitamin D and leukocyte telomere dynamics; but for the moment, our data suggest another potential benefit of vitamin D—on the aging process and age-related disease.