The Rate of Increase of Short Telomeres Predicts Longevity in Mammals

Abstract

Aberrantly short telomeres result in decreased longevity in both humans and mice with defective telomere maintenance. Normal populations of humans and mice present high interindividual variation in telomere length, but it is unknown whether this is associated with their lifespan potential. To address this issue, we performed a longitudinal telomere length study along the lifespan of wild-type and transgenic telomerase reverse transcriptase mice. We found that mouse telomeres shorten ∼100 times faster than human telomeres. Importantly, the rate of increase in the percentage of short telomeres, rather than the rate of telomere shortening per month, was a significant predictor of lifespan in both mouse cohorts, and those individuals who showed a higher rate of increase in the percentage of short telomeres were also the ones with a shorter lifespan. These findings demonstrate that short telomeres have a direct impact on longevity in mammals, and they highlight the importance of performing longitudinal telomere studies to predict longevity.

Telomere shortening in neurological disorders: an abundance of unanswered questions

“…Short telomeres in immune cells, astrocytes and neurons could enhance oxidative stress-dependent senescence and the associated secretion of pro-inflammatory mediators (senescence-associated secretory phenotype) that may enhance the disease progression [6, 38, 44]. Based on the existing literature it appears that the shortest telomeres within a cell have the most pronounced effect on cell phenotype and senescence [45, 46]. At present it is unclear whether median telomere length as measured in all real-time PCR and in most Southern blot studies serves as a good indicator of cellular phenotype.…”

Therapeutic effect of androgen therapy in a mouse model of aplastic anemia produced by short telomeres

“…Consequently, cells reaching a critical short telomere length enter into cellular senescence. [8][9][10][11] In contrast to most somatic cells, adult stem cells retain basal telomerase activity which leads to decelerated telomere attrition in these compartments, although eventually these cells also show telomere shortening associated with the aging process. 12 Conversely, impaired telomerase function, for instance by virtue of Tert haploinsufficiency, leads to accelerated telomere shortening in the stem cell compartments which prematurely limits the potential for hematopoietic stem cell proliferation and tissue renewal capacity, leading to the onset of different diseases.…”

Transgenerational Effects of PTSD or Traumatic Stress: Do Telomeres Reach Across the Generations?

“…Thus, telomeres act as the mitotic clocks of our body, allowing a mitotic cell only to replicate itself for a certain number of times until its telomeres shorten down to a critical length and therefore lead to cellular senescence [27]. This was elegantly illustrated in a longitudinal study conducted on transgenic mice, where the rate of increase in the percentage of short telomeres was predictive of the mice' life expectancy [28], and where telomerase-deficient cells (see below) with single short telomeres caused an earlier onset of senescence [29].…”