Human insulin/IGF-1 and familial longevity at middle age

Rozing, Maarten P.; Westendorp, Rudi G.J.; Frölich, Marijke; Craen, Anton J. M. de; Beekman, Marian; Heijmans, Bastiaan T.; Mooijaart, Simon P.; Blauw, G. J.; Slagboom, P. Eline; Heemst, Diana van

doi:10.18632/aging.100071

Cited by 68 publications

(70 citation statements)

References 32 publications

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“…We previously showed that long-lived family members from the LLS have a lower prevalence of CMV infection as compared with controls from the general population 31 , 33 . The levels of the other markers did not differ between long-lived family members and controls 28 , 29 . Most of these markers associated with LTL in the LLS (Supplementary Table S1, available as Supplementary data at IJE online).…”

Section: Resultsmentioning

confidence: 89%

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

Deelen

Beekman

Codd

et al. 2014

International Journal of Epidemiology

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Background: Human leukocyte telomere length (LTL) decreases with age and shorter LTL has previously been associated with increased prospective mortality. However, it is not clear whether LTL merely marks the health status of an individual by its association with parameters of immune function, for example, or whether telomere shortening also contributes causally to lifespan variation in humans.Methods: We measured LTL in 870 nonagenarian siblings (mean age 93 years), 1580 of their offspring and 725 spouses thereof (mean age 59 years) from the Leiden Longevity Study (LLS).Results: We found that shorter LTL is associated with increased prospective mortality in middle (30–80 years; hazard ratio (HR) = 0.75, P = 0.001) and highly advanced age (≥90 years; HR = 0.92, P = 0.028), and show that this association cannot be explained by the association of LTL with the immune-related markers insulin-like growth factor 1 to insulin-like growth factor binding protein 3 molar ratio, C-reactive protein, interleukin 6, cytomegalovirus serostatus or white blood cell counts. We found no difference in LTL between the middle-aged LLS offspring and their spouses (β = 0.006, P = 0.932). Neither did we observe an association of LTL-associated genetic variants with mortality in a prospective meta-analysis of multiple cohorts (n = 8165).Conclusions: We confirm LTL to be a marker of prospective mortality in middle and highly advanced age and additionally show that this association could not be explained by the association of LTL with various immune-related markers. Furthermore, the approaches performed here do not further support the hypothesis that LTL variation contributes to the genetic propensity for longevity.

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Section: Resultsmentioning

confidence: 89%

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

Deelen

Beekman

Codd

et al. 2014

International Journal of Epidemiology

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“…On the other hand, the MS proportion in GHD patients remained increased despite chronic rhGH replacement and resembles the metabolic profile of untreated GHD, suggesting that GHD may have irreversible effects on the cardiovascular system. In the context of increasing evidence for, on the one hand, a limited or even negative role of GH and IGF1 in cancer, longevity, and cardiovascular disease (34,35,36), and, on the other hand, the limited evidence for benefit of rhGH substitution in the elderly GHD population and long-term positive effects on QoL (37), long-term rhGH use in GHD adults should be critically re-evaluated. Third, we cannot exclude coexisting hypothalamic damage, especially in case of a history of large tumors with suprasellar extension (38).…”

Section: Discussionmentioning

confidence: 99%

Abnormal metabolic phenotype in middle-aged GH-deficient adults despite long-term recombinant human GH replacement

Claessen

Appelman‐Dijkstra²,

Pereira³

et al. 2014

European Journal of Endocrinology

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Background: Adult GH deficiency (GHD) is associated with increased cardiovascular mortality. Recombinant human GH (rhGH) replacement has beneficial short-term metabolic effects. Although these positive effects sustain during longer follow-up, the prevalence of the metabolic syndrome (MS) remains increased in comparison with population data not adjusted for the higher mean BMI in GHD adults. Objective: To explore whether middle-aged patients with proposed physiological rhGH replacement have been normalized with respect to MS and its individual components in comparison with the general population, adjusted for age, sex, and BMI. Methods: One hundred and sixty-one GHD patients (aged 40-70 years) were studied before the start and after 5 years of rhGH replacement, and were compared with 1671 subjects (aged 45-66 years) from the general population (NEO Study). Results: MS proportion in GHD patients was 41.0% before the start of rhGH suppletion, increasing to 53.4% after 5 years (PZ0.007). Despite chronic rhGH replacement, GHD patients had a 1.3-times higher MS proportion than the general population, independently of age, sex, and BMI (95% CI 1.1-1.5, PZ0.008). The GHD population showed a different metabolic profile than the general population with similar BMI: an increased risk of hypertriglyceridemia (adjusted prevalence ratio (PR) 2.0, 95% CI 1.7-2.3) and low HDL-C (adjusted PR 1.8, 95% CI 1.5-2.2), but less hyperglycemia (adjusted PR 0.5, 95% CI 0.4-0.7). Conclusions: Despite 5 years of rhGH replacement, GHD patients still have a different metabolic profile and more frequently MS than the general population. These differences were independent of BMI, and resemble the unfavorable metabolic profile of untreated GHD patients, pointing to question the long-term benefits of rhGH replacement.

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“…Abnormalities in the insulin signaling pathway generate age-related diseases and increased mortality, whereas the growth hormone (GH)/IGF-1 axis could potentially modulate longevity in many species. Moreover in humans, an age-related decline in IGF-1 levels occurs, and at old age, low IGF-1 levels are Aging and Disease • Volume 6, Number 2, April 2015 115 associated with frailty, poor nutrition and cognitive decline and an increased risk of death [129,130]. The aging process is altered or accelerated when metabolic and cardiovascular diseases are present and the risk of diseases increases with age.…”

Section: Aging and Methabolic Syndromementioning

confidence: 99%

Metabolic Syndrome, Aging and Involvement of Oxidative Stress

Bonomini¹,

Rodella²,

Rezzani³

2015

Aging and disease

463

307

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ABSTRACT:The prevalence of the metabolic syndrome, a cluster of cardiovascular risk factors associated with obesity and insulin resistance, is dramatically increasing in Western and developing countries. This disorder consists of a cluster of metabolic conditions, such as hypertriglyceridemia, hyper-low-density lipoproteins, hypo-high-density lipoproteins, insulin resistance, abnormal glucose tolerance and hypertension, that-in combination with genetic susceptibility and abdominal obesity-are risk factors for type 2 diabetes, vascular inflammation, atherosclerosis, and renal, liver and heart diseases. One of the defects in metabolic syndrome and its associated diseases is excess of reactive oxygen species. Reactive oxygen species generated by mitochondria, or from other sites within or outside the cell, cause damage to mitochondrial components and initiate degradative processes. Such toxic reactions contribute significantly to the aging process. In this article we review current understandings of oxidative stress in metabolic syndrome related disease and its possible contribution to accelerated senescence.

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Human insulin/IGF-1 and familial longevity at middle age

Cited by 68 publications

References 32 publications

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

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

Abnormal metabolic phenotype in middle-aged GH-deficient adults despite long-term recombinant human GH replacement

Metabolic Syndrome, Aging and Involvement of Oxidative Stress

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