Growth hormone secretion is diminished and tightly controlled in humans enriched for familial longevity

Spoel, Evie van der; Jansen, Steffy W.; Akintola, Abimbola A.; Ballieux, Bart E.; Cobbaert, Christa; Slagboom, P. Eline; Blauw, Gerard J.; Westendorp, Rudi G. J.; Pijl, Hanno; Roelfsema, Ferdinand; Heemst, Diana van

doi:10.1111/acel.12519

Cited by 61 publications

(25 citation statements)

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“…Indeed, in the same study population, comprising men and women, offspring had a 59.9% higher total TSH secretion and a higher temporal correlation between TSH and fT3 compared to controls (13, 14). Furthermore, GH secretion was lower and tighter controlled in the offspring compared to controls (15). When restricted to men only, which is a sample identical to the sample of men used in the current study, differences of similar magnitude were found in TSH secretion, temporal TSH–fT3 correlation, GH secretion, and GH ApEn.…”

Section: Discussionmentioning

confidence: 93%

“…It was found that TSH secretion was higher and TSH–fT3 temporal relationship was stronger in the offspring compared to controls (13, 14). Furthermore, we found that GH secretion was diminished and tightly controlled in offspring compared to controls (15). However, we did not find an association between familial longevity and cortisol secretion under resting conditions (16).…”

Section: Introductionmentioning

confidence: 80%

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Familial Longevity Is Not Associated with Major Differences in the Hypothalamic–Pituitary–Gonadal Axis in Healthy Middle-Aged Men

Spoel¹,

Roelfsema²,

Jansen³

et al. 2016

Front. Endocrinol.

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ContextA trade-off between fertility and longevity possibly exists. The association of the male hypothalamic–pituitary–gonadal (HPG) axis with familial longevity has not yet been investigated.ObjectiveTo study 24-h hormone concentration profiles of the HPG axis in men enriched for familial longevity and controls.DesignWe frequently sampled blood over 24 h in 10 healthy middle-aged male offspring of nonagenarian participants from the Leiden Longevity Study together with 10 male age-matched controls. Individual 24-h luteinizing hormone (LH) and testosterone concentration profiles were analyzed by deconvolution analyses to estimate secretion parameters. Furthermore, the temporal relationship between LH and testosterone was assessed by cross-correlation analysis. We used (cross-)approximate entropy to quantify the strength of feedback and/or feedforward control of LH and testosterone secretion.ResultsMean [95% confidence interval (CI)] total LH secretion of the offspring was 212 (156–268) U/L/24 h, which did not differ significantly (p = 0.51) from the total LH secretion of controls [186 (130–242) U/L/24 h]. Likewise, mean (95% CI) total testosterone secretion of the offspring [806 (671–941) nmol/L/24 h] and controls [811 (676–947) nmol/L/24 h] were similar (p = 0.95). Other parameters of LH and testosterone secretion were also not significantly different between offspring and controls. The temporal relationship between LH and testosterone and the strength of feedforward/feedback regulation within the HPG axis were similar between offspring of long-lived families and controls.ConclusionThis relatively small study suggests that in healthy male middle-aged participants, familial longevity is not associated with major differences in the HPG axis. Selection on both fertility and health may in part explain the results.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 80%

Familial Longevity Is Not Associated with Major Differences in the Hypothalamic–Pituitary–Gonadal Axis in Healthy Middle-Aged Men

Spoel¹,

Roelfsema²,

Jansen³

et al. 2016

Front. Endocrinol.

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“…Thus, exceptional longevity in humans has been associated with reduced IGF-1 levels ( Milman et al, 2014 ) and insulin/IGF-1 composite signaling score ( van Heemst et al, 2005 ). In many populations, shorter people live longer ( Samaras, 2007 ; He et al, 2014 ), and offspring of long-lived families secrete less GH than their spouses ( van der Spoel et al, 2016 ). Moreover, mortality is increased in individuals with pathologic excess of GH ( Baumann, 1987 ).…”

Section: Introductionmentioning

confidence: 99%

Impact of Growth Hormone-Related Mutations on Mammalian Aging

Bartke

Quainoo

2018

Front. Genet.

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Mutations of a single gene can lead to a major increase in longevity in organisms ranging from yeast and worms to insects and mammals. Discovering these mutations (sometimes referred to as “longevity genes”) led to identification of evolutionarily conserved molecular, cellular, and organismal mechanisms of aging. Studies in mice provided evidence for the important role of growth hormone (GH) signaling in mammalian aging. Mice with mutations or gene deletions leading to GH deficiency or GH resistance have reduced body size and delayed maturation, but are healthier and more resistant to stress, age slower, and live longer than their normal (wild type) siblings. Mutations of the same genes in people can provide remarkable protection from age-related disease, but have no consistent impact on lifespan. Ongoing research indicates that genetic defects in GH signaling are linked to extension of healthspan and lifespan via a variety of interlocking mechanism, including improvements in genome and stem cell maintenance, stress resistance, glucose homeostasis, and thermogenesis, along with reductions in the mechanistic target of rapamycin (mTOR) C1 complex signaling and in chronic low grade inflammation.

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“… 11 , 12 A recent study revealed that the total 24-hour secretion of GH was lower in middle-aged offspring of long-lived families than in their partners. 13 …”

Section: Introductionmentioning

confidence: 99%

Somatic growth, aging, and longevity

Bartke

2017

npj Aging Mech Dis

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Although larger species of animals typically live longer than smaller species, the relationship of body size to longevity within a species is generally opposite. The longevity advantage of smaller individuals can be considerable and is best documented in laboratory mice and in domestic dogs. Importantly, it appears to apply broadly, including humans. It is not known whether theses associations represent causal links between various developmental and physiological mechanisms affecting growth and/or aging. However, variations in growth hormone (GH) signaling are likely involved because GH is a key stimulator of somatic growth, and apparently also exerts various “pro-aging” effects. Mechanisms linking GH, somatic growth, adult body size, aging, and lifespan likely involve target of rapamycin (TOR), particularly one of its signaling complexes, mTORC1, as well as various adjustments in mitochondrial function, energy metabolism, thermogenesis, inflammation, and insulin signaling. Somatic growth, aging, and longevity are also influenced by a variety of hormonal and nutritional signals, and much work will be needed to answer the question of why smaller individuals may be likely to live longer.

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Growth hormone secretion is diminished and tightly controlled in humans enriched for familial longevity

Cited by 61 publications

References 46 publications

Familial Longevity Is Not Associated with Major Differences in the Hypothalamic–Pituitary–Gonadal Axis in Healthy Middle-Aged Men

Familial Longevity Is Not Associated with Major Differences in the Hypothalamic–Pituitary–Gonadal Axis in Healthy Middle-Aged Men

Impact of Growth Hormone-Related Mutations on Mammalian Aging

Somatic growth, aging, and longevity

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