Leukocyte telomere length associates with prospective mortality independent of immune-related parameters and known genetic markers

Deelen, Joris; Beekman, Marian; Codd, Veryan; Trompet, Stella; Broer, Linda; Hägg, Sara; Fischer, Krista; Thijssen, Peter; Suchiman, H. Eka D.; Postmus, Iris; Uitterlinden, André G.; Hofman, Albert; Craen, Anton J. M. de; Metspalu, Andres; Pedersen, Nancy L.; Duijn, Cornelia M. van; Jukema, J. Wouter; Houwing-Duistermaat, Jeanine J.; Samani, Nilesh J.; Slagboom, P. Eline

doi:10.1093/ije/dyt267

Cited by 95 publications

(67 citation statements)

References 43 publications

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“…Other recent meta-analyses support the concurrent associations between short telomeres and diabetes (8) and several cancers (9,10). Several studies indicate that short telomeres from varied sources, including leukocytes and saliva, are related to early mortality (11)(12)(13)(14)(15)(16)(17), including a study with >60,000 adults (18), although null studies also exist (19)(20)(21)(22).…”

mentioning

confidence: 89%

Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study

Puterman

Gemmill

Karasek

et al. 2016

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

141

102

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Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is a marker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging. cellular aging | telomeres | lifespan adversity | childhood adversity A ging cells play a crucial role in the pathogenesis of noncommunicable diseases, and telomere shortening in cells plays a part of this aging process (1, 2). Telomeres are DNAprotein caps at the ends of chromosomes that protect genetic material from degradation, and their lengths indicate cellular aging (2, 3). Experiments in rodents implicate shortened telomeres and lower activity of telomerase, the enzyme that lengthens telomeres, as causes of mitochondrial and tissue damage associated with disease pathogenesis (4-6).Telomere length is linked cross-sectionally and prospectively with human disease states in many studies. A recent meta-analysis suggests that individuals with observed short leukocyte telomeres are at an ∼80% increased risk of concurrent reports of cardiovascular disease and an ∼40% increased risk of developing cardiovascular disease in the future (7). Other recent meta-analyses support the concurrent associations between short telomeres and diabetes (8) and several cancers (9, 10). Several studies indicate that short telomeres from varied sources, including leukocytes and saliva, are related to early mortality (11-17), including a study with >60,000 adults (18), although null studies also exist (19)(20)(21)(22).Although these studies suggest that telomere length plays a role in disease, they are observational, and studies directly linking genetics...

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confidence: 89%

Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study

Puterman

Gemmill

Karasek

et al. 2016

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

141

102

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“…The age-dependent shortening of telomeres is coupled with shortened lifespan and reduced capacity to respond to cellular stress (91,277). With physiological aging, mouse cells maintain relatively long telomeres during their first year of life, which is followed by a marked loss of telomeric sequences and cell regenerative capacity at 2 years of age (37,152).…”

Section: Cellular and Organism Agingmentioning

confidence: 99%

Aging Effects on Cardiac Progenitor Cell Physiology

Rota

Goichberg

Anversa

et al. 2015

Comprehensive Physiology

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Cardiac aging has been confounded by the concept that the heart is a postmitotic organ characterized by a predetermined number of myocytes, which is established at birth and largely preserved throughout life until death of the organ and organism. Based on this premise, the age of cardiac cells should coincide with that of the organism; at any given time, the heart would be composed of a homogeneous population of myocytes of identical age. The discovery that stem cells reside in the heart and generate cardiac cell lineages has imposed a reconsideration of the mechanisms implicated in the manifestations of the aging myopathy. The progressive alterations of terminally differentiated myocytes, and vascular smooth muscle cells and endothelial cells may represent an epiphenomenon dictated by aging effects on cardiac progenitor cells (CPCs). Changes in the properties of CPCs with time may involve loss of self-renewing capacity, increased symmetric division with formation of daughter committed cells, partial depletion of the primitive pool, biased differentiation to the fibroblast fate, impaired ability to migrate, and forced entry into an irreversible quiescent state. Telomere shortening is a major variable of cellular senescence and organ aging, and support the notion that CPCs with critically shortened or dysfunctional telomeres contribute to myocardial aging and chronic heart failure. These defects constitute the critical variables that define the aging myopathy in humans. Importantly, a compartment of functionally competent human CPCs persists in the decompensated heart pointing to stem cell therapy as a novel form of treatment for the aging myopathy.

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“…The ramifications of LTL dynamics for human health are an area of active research. Although short LTL is associated with increased risk of atherosclerotic cardiovascular disease [5][6][7] and diminished longevity, [8][9][10] long LTL is associated with major cancers, including melanoma, 11 adenocarcinoma of the lung, 12 cancers of the breast 13 and pancreas, 14 and aggressive cancer of the prostate. 15 LTL research has been predominantly performed in adults.…”

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confidence: 99%

Leukocyte Telomere Length in Newborns: Implications for the Role of Telomeres in Human Disease

Factor-Litvak¹,

Süsser

Kezios³

et al. 2016

Pediatrics

191

192

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BACKGROUND AND OBJECTIVE: In adults, leukocyte telomere length (LTL) is variable, familial, and longer in women and in offspring conceived by older fathers. Although short LTL is associated with atherosclerotic cardiovascular disease, long LTL is associated with major cancers. The prevailing notion is that LTL is a "telomeric clock, " whose movement (expressed in LTL attrition) reflects the pace of aging. Accordingly, individuals with short LTL are considered to be biologically older than their peers. Recent studies suggest that LTL is largely determined before adulthood. We examined whether factors that largely characterize LTL in adults also influence LTL in newborns.

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Leukocyte telomere length associates with prospective mortality independent of immune-related parameters and known genetic markers

Cited by 95 publications

References 43 publications

Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study

Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study

Aging Effects on Cardiac Progenitor Cell Physiology

Leukocyte Telomere Length in Newborns: Implications for the Role of Telomeres in Human Disease

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