Reviewing Associations Between Physical Activity and Loss of Average Telomere Length with Age

Telomeres are repeated DNA sequences at the ends of chromosomes. With each cell division a little telomere length is lost, and this is an important part of the countdown mechanism that limits replication of somatic cells. Somatic cells with short telomeres become senescent or self-destruct. Stem cells, on the other hand, use telomerase to lengthen their telomeres, and thus produce daughter somatic cells with long telomeres throughout a lifetime. This two-tier system of privileged stem cells and limited somatic cells, present in near all animals, keeps the risk of cancer low enough for evolutionary success, while still allowing for tissue maintenance and cell turnover.

Average telomere length in tissues declines with age, and this is largely a function of loss of stem cell activity. There are fewer replacement cells with long telomeres. Telomere length is usually measured in immune cells in a blood sample, however, and here there are many more factors at work to muddy the waters. Immune cells will replicate at quite different rates from day to day, depending circumstances ranging from stress to infection. In human studies, telomere length only exhibits associations with aging - or with interventions known to modestly slow aging - in the statistics of large groups. Even then many studies fail to find a good correlation with diet, exercise, and the like. Thus for any given individual there usually isn't much to learn from a measure of telomere length, or a change in that measure over time.

Physical activity, a modulator of aging through effects on telomere biology

Telomere length (TL) varies greatly between species. At birth, every human individual has a specific TL that ranges between 5 to 15 kb. Throughout life telomeres shorten continuously with a rate between 20-50 bp due to the end-replication phenomenon, oxidative stress, and other modulating factors. However, telomere shortening rates and consequently also average TL vary amongst different tissue types, which is at least partly explained by tissue-specific proliferation rates. In dividing cells, the end replication problem is an important driver of telomere shortening that can be modified by other factors, such as oxidative stress or inflammation. In postmitotic cells instead oxidative stress can directly damage telomeric DNA and drive cells into senescence.

The TL of peripheral blood leucocytes (LTL) has gained substantial interest as a potential marker of biological age. Mean LTL in adults is approximately 11 kb and declines with an annual rate of 30-35 bp. Telomere attrition is most pronounced during the first two years of life, which are characterized by rapid somatic growth. The shortening of telomeres is not a unidirectional process since the reverse-transcriptase telomerase is capable of adding to telomeric ends. However, most somatic cells do not express telomerase. Detectable levels of telomerase activity can typically be found in germ line and embryonic stem cells, immune cells, and in cancer cells.

Regular exercise is a well-established approach to reduce the risk of morbidity and premature mortality. Prospective cohort studies demonstrate that men and women who regularly exercise, have a 30% lower all-cause mortality risk than sedentary individuals. In the older persons the beneficial effects of regular physical activity (above 200 minutes a day) are even more pronounced reaching up to 40% or more mortality risk reduction. Besides a substantial reduction of mortality, regular exercise also reduces the incidence and progression of coronary heart disease, hypertension, stroke, diabetes, metabolic syndrome, colon cancer, breast cancer, and depression. Despite the existence of robust evidence for multiple health benefits of regular exercise, the underlying mechanisms are insufficiently understood. General key mechanisms that drive the process of aging include the accumulation of genetic damage, epigenetic modifications, and shortening of telomeres. It has been speculated that exercise can help preserve TL through the induction of telomerase.

Despite robust evidence from cross-sectional and prospective intervention studies, not all previously published analyses support a relationship between exercise and telomere biology, however. For example, in a cross-sectional and longitudinal analyses of 582 older adults, researchers found no consistent relationship between physical activity and LTL.

Telomere research has gained much attention in the previous decade for its potential use and promise as a future therapeutic target, disease management, and measurement of genomic aging. Interventions, such as physical activity, that target the deleterious processes of aging have concomitantly created interest in the area of lifestyle and aging related research. Largely, the available physical activity data do not exclude that an association between regular exercise and TL exists. However, to date, the observed results from human studies are skewed largely by associations and observational or cross-sectional data. In light of the limited data, available evidence suggests altogether, that regular, and consistent physical activity over an extended period of time may assist with preservation of telomeres and cellular aging. Nevertheless, conflicting and a lack of consistent findings from the existing evidence, and particularly from the few available mechanistic studies means there is much more to explore and understand, prior to measurements such as TL will be adopted clinically.

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