Rise in Insulin Resistance Is Associated With Escalated Telomere Attrition

Gardner, J. P.; Li, Shengxu; Srinivasan, Sathanur R.; Chen, Wei; Kimura, Masayuki; Lu, Xingrong; Berenson, Gerald S.; Aviv, Abraham

doi:10.1161/01.cir.0000163550.70487.0b

Cited by 332 publications

(272 citation statements)

References 38 publications

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“…We also have found that the prenatally stressed individuals in this cohort exhibited insulin and leptin resistance, as well as a higher BMI (31). As insulin resistance is associated with chronological age, and longstanding insulin resistance can accelerate biological aging (58)(59)(60), it is possible that insulin resistance also may have contributed to more rapid cellular aging in the PSG individuals. Notably, we have described in this cohort alterations in the regulation of the hypothalamic-pituitaryadrenal axis in the PSG individuals (34).…”

Section: Discussionsupporting

confidence: 52%

Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood

Entringer

Epel

Kumsta

et al. 2011

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

352

244

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Leukocyte telomere length (LTL) is a predictor of age-related disease onset and mortality. The association in adults of psychosocial stress or stress biomarkers with LTL suggests telomere biology may represent a possible underlying mechanism linking stress and health outcomes. It is, however, unknown whether stress exposure in intrauterine life can produce variations in LTL, thereby potentially setting up a long-term trajectory for disease susceptibility. We, therefore, as a first step, tested the hypothesis that stress exposure during intrauterine life is associated with shorter telomeres in adult life after accounting for the effects of other factors on LTL. LTL was assessed in 94 healthy young adults. Forty-five subjects were offspring of mothers who had experienced a severe stressor in the index pregnancy (prenatal stress group; PSG), and 49 subjects were offspring of mothers who had a healthy, uneventful index pregnancy (comparison group; CG). Prenatal stress exposure was a significant predictor of subsequent adult telomere length in the offspring (178-bp difference between prenatal stress and CG; d = 0.41 SD units; P < 0.05). The effect was substantially unchanged after adjusting for potential confounders (subject characteristics, birth weight percentile, and early-life and concurrent stress level), and was more pronounced in women (295-bp difference; d = 0.68 SD units; P < 0.01). To the best of our knowledge, this study provides the first evidence in humans of an association between prenatal stress exposure and subsequent shorter telomere length. This observation may help shed light on an important biological pathway underlying the developmental origins of adult health and disease risk.developmental programming | fetal origin

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Section: Discussionsupporting

confidence: 52%

Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood

Entringer

Epel

Kumsta

et al. 2011

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

352

244

View full text Add to dashboard Cite

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“…Though highly variable, it is heritable [1][2][3][4][5][6] and longer in women than men [1,3,4,[6][7][8][9]. Environmental factors, including smoking [3,10], obesity [9][10][11], psychological stress [12] and low socio-economic status (SES) [13] are ostensibly associated with shortened LTL, underscoring the roles of not only genetic factors but also the environment in fashioning leukocyte telomere dynamics (length and attrition rate). Shortened LTL is also observed in individuals with aging-related diseases, including hypertension [1,7], insulin resistance [11,14,15], atherosclerosis [16,17], myocardial infarction [16,18,19], stroke [9] and dementia [20,21].…”

Section: Introductionmentioning

confidence: 99%

Offspring's Leukocyte Telomere Length, Paternal Age, and Telomere Elongation in Sperm

Kimura¹,

Cherkas²,

Kato³

et al. 2005

PLoS Genet

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Leukocyte telomere length (LTL) is a complex genetic trait. It shortens with age and is associated with a host of agingrelated disorders. Recent studies have observed that offspring of older fathers have longer LTLs. We explored the relation between paternal age and offspring's LTLs in 4 different cohorts. Moreover, we examined the potential cause of the paternal age on offspring's LTL by delineating telomere parameters in sperm donors. We measured LTL by Southern blots in Caucasian men and women (n¼3365), aged 18-94 years, from the Offspring of the Framingham Heart Study (Framingham Offspring), the NHLBI Family Heart Study (NHLBI-Heart), the Longitudinal Study of Aging Danish Twins (Danish Twins), and the UK Adult Twin Registry (UK Twins). Using Southern blots, Q-FISH, and flow-FISH, we also measured telomere parameters in sperm from 46 young (,30 years) and older (.50 years) donors. Paternal age had an independent effect, expressed by a longer LTL in males of the Framingham Offspring and Danish Twins, males and females of the NHLBI-Heart, and females of UK Twins. For every additional year of paternal age, LTL in offspring increased at a magnitude ranging from half to more than twice of the annual attrition in LTL with age. Moreover, sperm telomere length analyses were compatible with the emergence in older men of a subset of sperm with elongated telomeres. Paternal age exerts a considerable effect on the offspring's LTL, a phenomenon which might relate to telomere elongation in sperm from older men. The implications of this effect deserve detailed study.Citation: Kimura M, Cherkas LF, Kato BS, Demissie S, Hjelmborg JB, et al. (2008) Offspring's leukocyte telomere length, paternal age, and telomere elongation in sperm. PLoS Genet 4(2): e37.

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“…Critically short telomeres may trigger replicative senescence, albeit other processes, including the capped/ uncapped telomeric status and telomerase activity, are major determinants in this phenomenon. Thus, TL largely registers the replicative history, the cumulative oxidative burden, and, in part, the proliferative potential of somatic cells in culture [87]. The experiments show that the rate of telomere shortening in vitro is modulated by oxidative stress as well as by differences in antioxidative defense capacity between cell strains [88].…”

Section: Clinical Disorders Associated With Age-dependent Telomere Lomentioning

confidence: 91%

“…Shorter TL in leukocytes has been associated cross-sectionally with CVD and its risk factors, including pulse pressure and vascular aging [1,86,[95][96][97], obesity [87,98,99], vascular dementia [88,100], diabetes [98,[101][102][103][104], coronary artery disease (CAD) [1,105,106], myocardial infarction (MI) [107] although not in all studies [108], and cellular turnover and exposure to oxidative and inflammatory damage in chronic obstructive pulmonary disease (COPD) [109]. Leukocyte TL correlates with a subset of measures of cognitive performance, suggesting that it might be a biomarker of cognitive aging in women before the onset of dementia [110].…”

Section: Clinical Disorders Associated With Age-dependent Telomere Lomentioning

confidence: 99%

Hormone-brain-aging relationships, broadly reactive with imidazole-containing dipeptides: targeting of telomere attrition as an aging biomarker and dynamic telomerase activity flirting

Babizhayev¹,

Vishnyakova

Yegorov

2014

Journal of Basic and Clinical Physiology and Pharmacology

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It has been documented that telomere-associated cellular senescence may contribute to certain age-related disorders, and telomere length (TL) may be an informative biomarker of healthy aging. Hormone-brain-aging behaviormodulated telomere dynamics and changes in telomerase activity are consistent elements of cellular alterations associated with changes in proliferative state, and these processes are consequently considered as the new therapeutic drug targets for physiological control with advanced drug delivery and nutritional formulations. We raise and support a therapeutic concept of using nonhydrolyzed forms of naturally occurring neuron-specific imidazole dipeptide-based compounds carnosine and carcinine, making it clinically possible that slowing down the rate of telomere shortening could slow down the human aging process in specific tissues where proliferative senescence is known to occur, with the demonstrated evidence of telomere shortening that appeared to be a hallmark of oxidative stress and disease. Carnosine released from skeletal muscle during exercise may be transported into the hypothalamic tuberomammillary nucleus (TMN) histamine neurons and hydrolyzed. The resulting L-histidine may subsequently be converted into histamine, which could be responsible for the effects of carnosine on neurotransmission and hormone-like antiaging physiological function. The preliminary longitudinal studies of elderly individuals suggest that longer telomeres are associated with better survival, and an advanced oral nutritional support with nonhydrolyzed carnosine (or carcinine and patented compositions thereof) is a useful therapeutic tool for a critical TL maintenance that may fundamentally be applied in the treatment of age-related sight-threatening eye disorders, prolonged life expectancy, increased survival and chronological age of an organism in health control, smoking behavior, and disease."Our pleasures were simple-they included survival." -Dwight D. Eisenhower, 34th President of the United States, 1953States, -1961

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Rise in Insulin Resistance Is Associated With Escalated Telomere Attrition

Cited by 332 publications

References 38 publications

Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood

Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood

Offspring's Leukocyte Telomere Length, Paternal Age, and Telomere Elongation in Sperm

Hormone-brain-aging relationships, broadly reactive with imidazole-containing dipeptides: targeting of telomere attrition as an aging biomarker and dynamic telomerase activity flirting

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