Telomere length (TL) is a measure of replicative senescence (Aubert & Lansdorp, 2008
) and a proposed marker of biological aging (Bekaert et al., 2007
). TL decreases progressively with aging (Gilley et al., 2008
) and is associated with numerous pathologies (Brouilette et al., 2007
; Demissie et al., 2006
; Fitzpatrick et al., 2007
) and all-cause mortality (Cawthon et al., 2003
; Farzaneh-Far et al., 2008
). Moreover, cellular senescence induced by telomere shortening is a potential mechanism underlying reductions in physiological function with aging (Muller, 2009
; Fuster & Andrés, 2006
At any age, TL is determined by the combination of the TL at birth and the rate of age-related decline (Aubert & Lansdorp, 2008
). Despite its biological and biomedical importance, the factors that influence the age-associated decrease in TL are incompletely understood, particularly with regard to factors that may act to preserve TL. In this context, habitual aerobic exercise and high aerobic exercise capacity generally are associated with better maintenance of cellular function with aging compared with a sedentary lifestyle. However, associations between TL and habitual physical activity are inconsistent (Cherkas et al., 2008
; Woo et al., 2008
; Ludlow et al., 2008
, Shin et al., 2008
) and there is no information on TL and objective measures of aerobic capacity.
Accordingly, we tested the hypothesis that TL is at least partially preserved with aging in humans who perform regular vigorous aerobic exercise, and is positively related to maximal aerobic exercise capacity. We studied 57 men and women: 15 young (18 – 32 years, 7 male) and 15 older (55 – 72 years) sedentary (9 male), and 10 young (7 male) and 17 older habitually exercising (11 male). Subjects were non-obese, non-smokers and healthy as assessed by medical history, physical examination, blood chemistries and exercise ECG (older subjects only). Sedentary subjects performed no regular aerobic exercise (< 2 days/week, < 30 min/day), whereas exercising subjects had performed regular vigorous aerobic exercise (≥ 5 days/week, > 45 min/day) for ≥5 years.
Leukocyte TL (LTL), the most commonly used human telomere sample and a proposed marker of systemic biological aging (Bekaert et al., 2007
; Aviv, 2002
; Cherkas et al., 2008
), was measured in genomic DNA extracted from isolated leukocytes using a modification of the Southern blot analysis described previously (Middleman et al., 2006
). Maximal oxygen consumption (VO2
max) was assessed during treadmill exercise and used as a measure of maximal aerobic exercise capacity as described earlier (DeSouza et al., 2000
). Subject characteristics were assessed using standard techniques described elsewhere (Pierce et al., 2008
). All measurements were performed after a 12-h fast and 24-h abstention from alcohol and physical activity. Group differences were determined by analysis of variance. Bivariate Pearson correlation analyses were used to assess relations of interest. Stepwise linear regression analysis was performed to identify independent predictors of LTL.
Several subject characteristics differed among the groups in the expected directions (). Diet composition and nutrient intake, adjusted for total calories, were similar among the groups (data not shown). LTL was shorter in the older (7059 ± 141 bp) vs. young (8407 ± 218) sedentary adults (P < 0.01, ). LTL of the older endurance-trained adults (7992 ± 169 bp) was ~900 bp greater than their sedentary peers (P < 0.01) and was not significantly different (P = 0.12) from young exercise-trained adults (8579 ± 413).
Figure 1 (A) Compared with sedentary (Sed) and exercising (Ex) young adults, mean LTL was shorter in sedentary, but not exercising older adults (*P < 0.01 vs. young groups and older exercising group). (B) Mean LTL is positively related to maximal aerobic (more ...)
LTL was positively related to VO2max in the overall sample (r = 0.44, P < 0.01, ) due to a positive correlation among the older adults (r = 0.44, P < 0.01), as there was no relation among young adults (r = −0.02, P = 0.92). Stepwise multiple regression analysis revealed that in the overall sample VO2max was the only variable that entered and independently explained 62% of the variance in LTL (R2 = 0.62, b = 0.51, P < 0.01), whereas in the older subjects alone VO2max explained 60% of the variance (R2 = 0.60, b = 0.077, P < 0.01) with age explaining an additional 28% (R2 = 0.88, b = −0.051, P < 0.01). The relation between LTL and VO2max in the overall and older groups was not affected by other subject characteristics. LTL did not correlate with leisure-time physical activity in any group (r = 0.15 – 0.28, P = 0.11 – 0.52). LTL was not influenced by the sex of the subjects (P = 0.21).
The results of the present study provide evidence that LTL is related to regular vigorous aerobic exercise and maximal aerobic exercise capacity with aging in healthy humans. LTL is not influenced by aerobic exercise status among young subjects, presumably because TL is intact (i.e., already normal) in sedentary healthy young adults. However, as LTL shortens with aging it appears that maintenance of aerobic fitness, produced by chronic strenuous exercise and reflected by higher VO2max, acts to preserve LTL.
The exact nature of these relations and the underlying mechanisms are not clear. Risk factors for cardiovascular disease may influence LTL (Chen et al., 2009
; Fitzpatrick et al., 2007
), but did not explain the relations with VO2
max in the present study. Habitual aerobic exercise modulates VO2
max, but as much as ~50% of the latter is determined primarily by genetic factors (Bouchard et al., 1998
). Shorter-term exercise training has no effect on LTL in humans or mice (Shin et al., 2008
; Werner et al., 2008
), but does modulate telomere-regulating proteins (Werner et al., 2008
). This may suggest that longer-term or more strenuous exercise is required to influence LTL. It also is possible that habitual exercise behavior, higher VO2
max and longer LTL all are part of the same phenotype expressed in some older adults. Although previous findings are inconsistent (Cherkas et al., 2008
; Ludlow et al., 2008
; Woo et al., 2008
), the fact that leisure-time physical activity was unrelated to LTL in our study suggests a more direct association with maximal aerobic exercise capacity.
In conclusion, LTL is preserved with age in endurance exercise-trained humans and is related to maximal aerobic exercise capacity among healthy older adults. This may represent a novel molecular mechanism linking vigorous habitual exercise/aerobic fitness to reduced cellular senescence and preserved physiological function with aging.