Sex-specific telomere length profiles and age-dependent erosion dynamics of individual chromosome arms in humans

Mayer, Susanne; Brüderlein, Silke; Perner, Sven; Waibel, I.; Holdenried, A.; Ciloglu, Neslisah; Hasel, Cornelia; Mattfeldt, Torsten; Nielsen, Kirsten; Möller, Peter

doi:10.1159/000089870

Cited by 135 publications

(124 citation statements)

References 69 publications

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“…When controlling for sex, age is not significantly correlated with LTL, potentially due to the narrow age range in our sample (M age = 21.21, SD = 1.54). These results are consistent with previous findings showing that, generally, males have shorter telomeres and higher erosion rates (61). In investigating the relationship between delay discounting and LTL, we consider sex and age as controls in the subsequent regression models.…”

Section: Resultssupporting

confidence: 90%

Delay discounting, genetic sensitivity, and leukocyte telomere length

Yim

Zhang

Shalev

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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In a graying world, there is an increasing interest in correlates of aging, especially those found in early life. Leukocyte telomere length (LTL) is an emerging marker of aging at the cellular level, but little is known regarding its link with poor decision making that often entails being overly impatient. Here we investigate the relationship between LTL and the degree of impatience, which is measured in the laboratory using an incentivized delay discounting task. In a sample of 1,158 Han Chinese undergraduates, we observe that steeper delay discounting, indexing higher degree of impatience, is negatively associated with LTL. The relationship is robust after controlling for health-related variables, as well as risk attitude-another important determinant of decision making. LTL in females is more sensitive to impatience than in males. We then asked if genes possibly modulate the effect of impatient behavior on LTL. The oxytocin receptor gene (OXTR) polymorphism rs53576, which has figured prominently in investigations of social cognition and psychological resources, and the estrogen receptor β gene (ESR2) polymorphism rs2978381, one of two gonadal sex hormone genes, significantly mitigate the negative effect of impatience on cellular aging in females. The current results contribute to understanding the relationship between preferences in decision making, particularly impatience, and cellular aging, for the first time to our knowledge. Notably, oxytocin and estrogen receptor polymorphisms temper accelerated cellular aging in young females who tend to make impatient choices.telomere length | delay discounting | risk attitude | oxytocin receptor | estrogen receptor

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Section: Resultssupporting

confidence: 90%

Delay discounting, genetic sensitivity, and leukocyte telomere length

Yim

Zhang

Shalev

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…1). As fundamental healthy control subjects, we included and reexamined the large cohort of normal women published by Perner et al (17) and Mayer et al (18), comprising newborns to centenarians. To our knowledge and to their own account, these individuals were healthy.…”

Section: Methodsmentioning

confidence: 99%

Lymphocytes of Type 2 Diabetic Women Carry a High Load of Stable Chromosomal Aberrations

Boehm

Möller²,

Högel³

et al. 2008

Diabetes

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OBJECTIVE-Diabetes is associated with an increased risk of death in women. Oxidative stress due to chronic hyperglycemia leads to the generation of reactive oxygen species and loss of chromosomal integrity. To clarify whether diabetes is a premature aging syndrome, we determined telomere erosion dynamics and occurrence of structural chromosomal aberrations in women of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study.RESEARCH DESIGN AND METHODS-Telomere lengths and karyotypes were examined in peripheral blood mononuclear cells. Regarding these parameters, surviving and deceased type 2 diabetic women of the LURIC study were compared with nondiabetic LURIC women with or without coronary heart disease and with healthy female control subjects.RESULTS-Significantly enhanced telomere attrition was seen in all LURIC subjects compared with healthy control subjects. Although the average telomere-length loss is equivalent to well Ͼ10 years of healthy aging, telomere erosion was not associated with outcome within the LURIC cohort. However, strikingly high numbers of stable chromosomal aberrations were found in type 2 diabetic women but not in LURIC disease control subjects or in healthy individuals. Furthermore, within the younger agegroups, deceased type 2 diabetes patients had significantly more marker chromosomes than the surviving type 2 diabetic patients.CONCLUSIONS-All women at high risk for cardiovascular death have accelerated telomere erosion, not caused by type 2 diabetes per se but likely linked to other risk factors, including dyslipidemia. By contrast, the occurrence of marker chromosomes is associated with type 2 diabetes and is a novel risk factor for type 2 diabetes-related early death. Diabetes 57:2950-2957, 2008 T ype 2 diabetes is characterized by increased morbidity and all-cause mortality (1,2). The combination of excess caloric intake and reduced physical activity leading to obesity, dyslipidemia, and hypertension increases the risk for diabetes and coronary heart disease (CHD). Recent data show that among diabetic men, the mortality rate has decreased significantly, whereas in diabetic women, no such trend was found (3). The all-cause mortality rate difference between diabetic and nondiabetic women is considerable. Therefore, the combination of diabetes with multiple risk factors identifies women at particularly high risk (2,4).The relative risk for morbidity and mortality in women with diabetes is increased compared with nondiabetic control subjects (2,5). Diabetes may therefore be regarded as a premature aging syndrome in which the overall metabolic shift leads to genotoxic stress that results in loss of chromosomal integrity (rev. in 6). Oxidative stress plays a crucial role in the pathogenesis of type 2 diabetes and in diabetes-associated complications. The generation of reactive oxygen species (ROS) is a common downstream mechanism whereby multiple by-products of glucose and (pro)inflammatory molecules exert adverse effects (7-11). DNA damage and telomere attrition can serve as marke...

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“…Nothing similar is possible with Southern analysis [Lansdorp et al, 1996;Londoño-Vallejo et al, 2001;Perner et al, 2003;Mayer et al, 2006]. Analyses of 20 metaphase and 20 interphase preparations from short-term T lymphocyte cultures from each of 15 individuals were analyzed using quantitative PNA FISH technology blind to dementia, FXTAS, and premutation status.…”

Section: Telomere Length Analysismentioning

confidence: 99%

Reduced telomere length in older men with premutation alleles of the fragile X mental retardation 1 gene

Jenkins

Tassone²,

et al. 2008

American J of Med Genetics Pt A

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Reduced telomere length has recently been reported in T lymphocytes of individuals with trisomy 21 Down syndrome (DS) and dementia. Shorter telomeres also have been documented in dyskeratosis congenita, cell senescence, Alzheimer disease, and neoplastic transformation. These observations suggest that similar shortening may occur in people with fragile X-associated tremor/ ataxia syndrome (FXTAS), which frequently is accompanied by dementia. To test this hypothesis, telomere length has been quantified in T lymphocytes from older male carriers of premutation FMR1 alleles, with or without FXTAS, and FXTAS with dementia. Shorter telomeres (relative to age-matched controls) were observed in 5/5 individuals with FXTAS and dementia, in 2/2 individuals with FXTAS without dementia, and in 3/3 individuals with the fragile X premutation only (p values ranged from <.001 to <.05; Student's t test), indicating that telomere shortening is associated with the premutation expansion of the FMR1 gene. The current study design allowed simultaneous comparisons among control, premutation, FXTAS, and FXTAS with dementia samples, and showed nearly equal degrees of shortening relative to controls among the three premutation sample groups. Thus, telomere shortening may serve as a biomarker for cellular dysregulation that may precede the development of the symptoms of FXTAS.

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Sex-specific telomere length profiles and age-dependent erosion dynamics of individual chromosome arms in humans

Cited by 135 publications

References 69 publications

Delay discounting, genetic sensitivity, and leukocyte telomere length

Delay discounting, genetic sensitivity, and leukocyte telomere length

Lymphocytes of Type 2 Diabetic Women Carry a High Load of Stable Chromosomal Aberrations

Reduced telomere length in older men with premutation alleles of the fragile X mental retardation 1 gene

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