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

Abstract

Aging is a complex process that is not well understood but involves finite changes at the genetic and epigenetic level. Physical activity is a well-documented modulator of the physiological process of aging. It has been suggested that the beneficial health effects of regular exercise are at least partly mediated through its effects on telomeres and associated regulatory pathways. Telomeres, the region of repetitive nucleotide sequences functioning as a “cap” at the chromosomal ends, play an important role to protect genomic DNA from degradation. Telomeres of dividing cells progressively shorten with age. Leucocyte telomere length (TL) has been associated with age-related diseases. Epidemiologic evidence indicates a strong relationship between physical activity and TL. In addition, TL has also been shown to predict all-cause and cardiovascular mortality. Experimental studies support a functional link between aerobic exercise and telomere preservation through activation of telomerase, an enzyme that adds nucleotides to the telomeric ends. However, unresolved questions regarding exercise modalities, pathomechanistic aspects and analytical issues limit the interpretability of available data. This review provides an overview about the current knowledge in the area of telomere biology, aging and physical activity. Finally, the capabilities and limitations of available analytical methods are addressed.

Telomere Length as a Marker of Biological Age: State-of-the-Art, Open Issues, and Future Perspectives

“…The implementation of LTL as routine marker into clinical practice is currently hampered by several unresolved pre-analytical and analytical issues (Semeraro et al, 2020 ). One serious problem is considerable inter-individual variability of LTLs which was repeatedly observed in molecular epidemiological studies across multiple populations and which may substantially complicate the interpretation of individual data (Bodelon et al, 2014 ).…”

“…Another important issue is that TL may substantially vary across various tissue types. There is also evidence that TL may vary even within the same organ depending on the site of sampling (Semeraro et al, 2020 ). However, in some cases, TLs may be correlated in different organs even despite these differences.…”

“…One more important methodological problem is that blood leukocytes are highly heterogeneous cell population which includes various cell types, such as lymphocytes, monocytes, granulocytes, etc. The composition of this cellular population is known to be highly variable, even in healthy persons, depending on various stress exposures (Semeraro et al, 2020 ). Different stressors may trigger a redistribution of leukocytes from immune reservoirs to the circulation and certain peripheral tissues (Dhabhar et al, 2012 ).…”

“…More specifically, if parental gametes are vulnerable to stress, then chromosomes, together with their telomere sequences which were shortened in consequence of stress exposure, can be directly transmitted to offspring thereby affecting health outcomes and longevity in subsequent generations. Adult-life exposures to environmental factors such as infection (Ilmonen et al, 2008 ), psycho-emotional stress (Epel et al, 2004 ; Boccardi and Boccardi, 2019 ; Mayer et al, 2019 ), nutrition (Canudas et al, 2020 ; Galié et al, 2020 ), physical activity (Semeraro et al, 2020 ), smoking (Astuti et al, 2017 ), alcohol consumption (Dixit et al, 2019 ), marital status (Chen et al, 2020 ), therapeutic interventions (Srinivas et al, 2020 ), etc. were also shown to have long-term impacts on TL.…”

No Time to Age: Uncoupling Aging from Chronological Time

“…Moreover, mice generated from ES cells with hyper-long telomeres show an increase in lifespan, are leaner and have a decrease in metabolic aging [ 41 ]. Importantly, environmental interventions such as calorie restriction and exercise have been shown to decelerate the telomeric clock in humans [ 42 , 43 ]. Taken together, these data support the notion that the loss of telomerase near the pluripotency to embryonic transition (PT) correlates with the onset of mortality of the soma and a clock-bound process that contributes to the eventual aging and death of the body.…”