In this study, we investigated the relationship between TL and adiposity using both cross-sectional and follow-up data. Our findings suggest that shorter TL may be a risk factor for increased adiposity. TL measured at baseline was significantly associated with several adiposity measures, including, % body fat, subcutaneous fat and leptin, but not with obesity, BMI or visceral fat. In our prospective analyses of 3 available adiposity measures, the direction of their relationship with TL remained the same but the significance was weaker. Furthermore, we also found TL to be associated with positive change in BMI and % body fat after 7 years of follow-up.
It might appear somewhat puzzling as to why only certain adiposity measures were associated with TL while some others were not. In our cohort composed of elderly individuals, quantitative traits showing stronger association with TL were also in higher correlations with each other (r = 0.66 – 0.80), whereas all other pair-wise correlation estimates were weaker (≤ 0.56) except for that between BMI and subcutaneous fat (0.76). There were also varying degrees of statistical power in analyses of different traits. Although our sample size was large, we still did not have sufficient power to detect the observed effects for visceral fat and BMI (power ≈ 0.6) while the power was sufficient for the other three adiposity measures. In addition, one question that comes to mind is whether BMI is a good measure of adiposity in the elderly. Some previous studies have suggested that BMI may not be as informative as a proxy for adiposity or an appropriate measure for defining obesity in older individuals (23
). This may help explain the lack of association between BMI/obesity and TL.
There are a handful of previous investigations on the association between TL and obesity-related traits, all of which considered obesity being a risk factor for shorter TL. Some studies found significant associations between shorter TL and obesity or higher levels of its related quantitative measures (16
) whereas others did not (19
). Yet no study has been conducted in the elderly. Some studies only provided correlation coefficients (16
), which tends to be less informative compared to association testing as it does not evaluate the magnitude of the effects. Weight, BMI, leptin and waist-to-hip ratio were most commonly investigated in earlier studies. BMI was inversely associated with TL in middle aged individuals (16
). We also observed a weak but negative relationship between TL and BMI, and a significantly negative association with % body fat in our cohort of elderly. Using BMI ≥ 30 kg/m2
to define obesity, MacEneaney et al. (19
) reported no difference in TL between normal and overweight/obese individuals. One study by Valdes et al. (16
) reported a negative correlation (r = −0.124, p < 0.0001) between TL and leptin, whereas another smaller study did not (27
). In our analysis of leptin, when unadjusted for % body fat, we observed a similar result as those reported by Valdes et al. (16
). However, we considered it informative to evaluate such as relationship independent of body fat, since leptin is produced by fat cells. As expected, we observed that shorter TL was associated with lower leptin levels after adjusting for the effect of % body fat. Leptin plays a role in appetite suppression and one would expect that higher leptin level be associated with better health, thus with longer TL. Two studies examined the effect of waist-to-hip ratio in TL and reported significantly negative association with TL (27
). We used measurements from CT scans to obtain more precise measures of regional adiposity and observed a significantly negative association of TL with subcutaneous fat, but not with visceral fat. Our study is novel in that we treated TL as a risk factor. It is interesting to see that while our study treated TL as a risk factor contrary to previous studies, we could still observe comparable findings mainly on the direction of the associations.
There are several advantages of our study. One of the main strengths is the prospective nature of our study with several repeated adiposity measures ascertained 7 years apart. This enabled us to test our hypothesis that TL may be a risk factor for increased adiposity in a prospective fashion. In addition, our study is the first large study to examine the association between TL and adiposity in a non-Caucasian sample, and our findings suggest that race did not appear to affect the association between adiposity and TL. The ages of our study subjects were notably older than previous studies, which provided evidence that the association between TL and adiposity observed in younger populaitons was also present in the elderly. However, as we did not have TL measured at follow-up, our study could not examine whether adiposity could be a risk factor for telomere shortening in a prospective fashion. Nevertheless, our observations suggest that TL may be considered a risk factor for adiposity. One possible limitation to the current study is that we measured TL in leukocytes as a proxy for TL in other tissues. However is well documented that TL measurement in easily accessible tissues such as blood could serve as a surrogate parameter for the relative telomere length in other tissues (29
In summary, we found that shortening of TL was associated with adiposity. However, whether telomere shortening is a cause or consequence of increased adiposity could not be determined based on our data alone. Although it may be possible that TL shortening is a consequence of increased adiposity due to elevated levels of oxidative stress (9
) and other factors, our study suggests their relationship may be more complicated. The possible biological mechanism(s) for these associations deserves further investigations. A better understanding of their relationship may have implication on our effort to reduce obesity burden and to promote healthy aging.