How “Reversible” Is Telomeric Aging?

Abstract

A critical question in human health is the malleability of telomere length. Telomere length, sampled at one point during adult life, is predictive of certain types of cancer and other immune and metabolicrelated diseases. We now know from basic studies that the telomere/telomerase maintenance system plays a causal role in accelerating biologic aging and promoting disease processes. One can develop short telomeres for a multitude of reasons. Historical factors such as genetics, prenatal conditions, and early adversity, contribute to adult telomere length; however, current stress and lifestyle are also associated. If these modifiable predictors are causal factors in telomere shortening, there is a tremendous opportunity to improve maintenance and possibly even lengthen telomeres with behavioral interventions. This minireview discusses our current understanding of telomere lengthening and questions facing the field. Several small-scale stress reduction/wellness studies show promising findings, suggesting that cell aging can be slowed or reversed in vivo over short periods. Moreover, possible mechanisms are discussed, that take into account actual telomeric lengthening, such as that which occurs through telomerase-mediated elongation, or mechanisms resulting in "pseudo-telomeric lengthening" as might occur from changes in cell type distribution. There is a strong need for more translational clinical to bench research to address mechanistic questions in experimental models. In addition, well-designed intervention research that examines both telomeres and potential mediators of change can further enhance our understanding of malleability, mechanism, and clinical implications of telomere lengthening. Cancer Prev Res; 5(10); 1163-8. Ó2012 AACR.A rapidly growing body of research suggests that one snapshot measure of leukocyte telomere length is predictive of age-related physiologic decline, onset of diseases of aging, such as cancer and dementia, and early mortality (1-3). Thus, it is not surprising that when people learn about telomeres, one of the most common questions is "Can telomeres be lengthened?" The answer is not so simple. While the quick answer is "yes," it is one that requires qualification and explanation. Here, we review what is known so far about telomere lengthening in humans, with respect to stress reduction interventions in particular, and address important questions to understand the mechanisms of apparent telomere lengthening. Telomeres Shorten . . . and LengthenTelomeres tend to shorten slowly over years of aging but are active and dynamic, especially when examined over short periods. In the early studies of telomeres in single-celled organisms called protozoa, Blackburn and Greider observed, "telomeres are dynamic structures in vivo, being acted on by shortening and lengthening activities" (4). They discovered telomerase, an intracellular enzyme that has an RNA reverse transcriptase component that lengthens telomeres. Telomerase-mediated elongation of telomeres occurs through de novo synthes...

The Influence of Alcohol Consumption, Cigarette Smoking, and Physical Activity on Leukocyte Telomere Length

“…While telomeres normally shorten over a period of decades, it has been hypothesized that sustained shorter-term increases in telomere length may alter the long-term trajectory of telomere attrition in such a way that decreases risk of age-related diseases (76). This is based on observations of increased lifespan in animal models with upregulated telomerase activity (77) and in human studies improvements in health that coincided with a modest increase in telomerase following behavioral interventions (60,78).…”

Leukocyte telomere length: Effects of schizophrenia, age, and gender

“…One marker of biological age is telomere length (TL), often measured in leukocytes (LTL), since it progressively declines with age and may be inversely related to diseases of aging and mortality (Bojesen, 2013;Cawthon et al, 2003;Mather et al, 2011;Muezzinler et al, 2013;Svensson et al, 2014). However, peak LTL (shortly after birth), the age at which a decline begins, the rate of decline, and when death interrupts the process, vary among individuals (Svensson et al, 2014), suggesting important interindividual differences in the rates of biological aging (Epel, 2012;Lindqvist et al, 2015;Muezzinler et al, 2013). Variability in telomere length among people of the same chronological age raises the possibility that telomere shortening is potentially modifiable (Bojesen, 2013).…”

Telomeres And Early Life Stress: A Review

“…7 Some individuals maintain and may even lengthen average LTL for some periods. The reasons for this are unknown, but relatively long telomeres tend to shorten over time, and relatively short telomeres tend to lengthen over time, possibly due to the preferential recruitment of reparative mechanisms such as telomerase activity (TA).…”