Average telomere length is currently usually measured in leukocytes obtained from a blood sample. When considering the statistics of a sizable population, average telomere length tends to trend downwards over a lifetime. Telomeres form a part of the complex mechanism that limits somatic cell replication: they shorten with each cell division, and cells with very short telomeres self-destruct or become senescent, ceasing to replicate in either case. Stem cells deliver a supply of new somatic cells with long telomeres to make up the numbers. So average telomere length is a blurred measure of stem cell activity and pace of cellular replication - and in the immune system the latter is highly variable, depending on the current state of health and presence of threats. Telomere length thus varies considerably between individuals of a similar age and health status, and also over quite short periods of time for any given individual. Even in smaller groups, the statistical association with aging can be weak to non-existent. All of this means that telomere length isn't all that helpful as a guide for medical decisions or as a way to evaluate the state of aging.
The associations between mortality and traditional biomarkers such as blood pressure, cholesterol, and body mass index (BMI) weaken with age. The search for a definitive aging biomarker is encumbered by the heterogeneity of cellular aging. Post-mitotic cells are not subjected to the replicative stresses experienced by mitotic cells; therefore, some tissues exhibit greater biological aging than others. The highly variable human lifespan highlights that the mere passage of chronological time is not an effective, isolated measure of aging. Biological aging refers to processes that proceed independently of chronological aging that reduce organismal viability and increase vulnerability. Telomeres are regarded by many as the heir apparent of aging biomarkers, recording both chronological and biological age.
A growing body of evidence also indicates that telomeres are responsive to habitual physical activity (PA). Despite the telomere's popular designation as a mitotic clock, the relationship between telomere length and aging is inconsistent and does not meet the requisite biomarker criteria. Closer examination of the association with PA also reveals inconsistencies and methodological confounders. The clinical and public interest in the PA-telomere association is predicated upon several tacit assumptions: (i) mean telomere length is causally associated with biological aging and age-related pathologies and (ii) PA can lengthen mean telomere length and that in doing so; (iii) PA will reduce biological aging and disease burden.
The proposed associations with aging and exercise are biologically plausible. Telomere length holds tantalizing promise as a biomarker; however, a host of evidential inconsistencies and paradoxes must be addressed. Leukocyte telomere length (LTL) is highly variable at birth, a metric influenced by genetic inheritance and paternal age at conception. It reflects lifelong exposure to oxidative and inflammatory burden yet childhood LTL has more predictive fidelity than LTL in adulthood or old age. Oscillating throughout the lifespan, even inexplicably lengthening despite advancing age, mean LTL differs between genders. Attrition rates also differ between genders and appear dependent upon initial telomere length. Shortening trajectories can be further influenced by variable exposure to a wide range of environmental stimuli. The association between PA is more questionable with 50% of studies failing to find a significant association.
Investigations into plausible mechanisms have returned promising yet inconsistent findings. The prevailing consensus is that exercise-induced reductions in oxidative stress and inflammation likely mediate the effect. The possibility that LTL is a physiological epiphenomenon cannot be excluded. Changes in LTL may simply be coincidental processes that reflect, without directly influencing, the primary mechanism. It is likely that telomere length per se is significant only in so much as it reflects the resultant phenotype via pathways such as senescence-associated inflammation. It has been proposed that evolutionary pressures have fine-tuned telomere length to reduce the risk of short and long telomere pathologies, namely atherosclerosis and cancer. The long-term consequences of manipulating telomere length are not well understood and should therefore be approached with equal measures of enthusiasm and evidence.