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The Paradoxical Lengthening of Telomeres in Somatic Tissues of the Very Old: Aging Effect Meets Birth‐Cohort Effect
Author(s) -
Stindl Reinhard
Publication year - 2016
Publication title -
journal of experimental zoology part b: molecular and developmental evolution
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 63
eISSN - 1552-5015
pISSN - 1552-5007
DOI - 10.1002/jez.b.22677
Subject(s) - telomere , center (category theory) , citation , somatic cell , cohort , perspective (graphical) , medicine , psychology , philosophy , library science , genetics , computer science , biology , artificial intelligence , chemistry , dna , gene , crystallography
Last year, a large cross-sectional study with interesting findings on telomere dynamics during human aging appeared in the journal Genetics (Lapham et al., 2015). Telomere length of saliva DNA samples showed a negative correlation with age up to 75 years; unexpectedly, age was correlated positively with longer telomeres in those older than 75 years. If, as proposed by the authors, this phenomenon might simply reflect a survival advantage at old age for those with longer telomeres (Lapham et al., 2015), one would expect to see a slow-rise pattern starting at age 60 years, when age-associated diseases begin to take their toll, but this is not the case (see Fig. 7 of (Lapham et al., 2015)). The reversal of telomere dynamics in both sexes occurs in participants aged 80 years. Most interestingly, in cross-sectional cancer data sets from the U.S. National Cancer Institute, after a sharp rise starting at middle age, cancer incidence patterns also reverse in participants aged 80 years (Stindl, 2008). (Replicative telomere erosion in somatic tissues during aging is causally involved in the genesis of carcinoma (Stindl, 2008) and other age-associated diseases.) Here, I propose that a progressive telomere loss between human generations—a model that was introduced 12 years ago (Stindl, 2004, 2014) and which was confirmed by a large study in 2015 (Holohan et al., 2015)—results in a birth-cohort effect that "compensates" for the telomere loss in somatic tissues during aging in the very old. Very old individuals ( 80 years) are members of previous generations and, on average, have bypassed the intergenerational telomere loss of at least two generations compared to young individuals (Fig. 1). Thus, I conclude that at very advanced ages, the cumulative birth-cohort effect results in a reversal of telomere dynamics in a cross-sectional data set, corresponding to 20 years of aging in somatic tissues in this age group. The possible underlying biological mechanism is outlined elsewhere (Stindl, 2004, 2011, 2014, 2016). The cumulative loss of telomere length between human generations (Stindl, 2004, 2014; Holohan et al., 2015) could explain the sudden appearance of the reversal at a certain advanced age, when tissue regeneration and therefore replicative telomere erosion in somatic tissues is slowing. The reason why the age-associated telomere-length-reversal in saliva samples is not seen in standard studies using blood samples is that very few mammalian blood cells contain DNA; i.e. white blood cells, and this highly variable population of immune cells responds to all sorts of stimuli, including hormones, stress, and infection. To summarize, the findings of Lapham and colleagues reported as a cross-sectional data set are proposed to result from the interference of two independent mechanisms, intergenerational telomere loss in the germline and replicative telomere erosion in somatic tissues during aging. Accordingly, a theoretical model of stable sperm telomeres and telomere erosion in oocytes has been introduced (Stindl, 2011, 2014, 2016). Longitudinal studies on human oocytes and sperms are required to test the hypothesis of transgenerational telomere erosion in the female germline (Stindl, 2016).