Dataset Information

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

ABSTRACT:

Context

A 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.

Objective

To study 24-h hormone concentration profiles of the HPG axis in men enriched for familial longevity and controls.

Design

We 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.

Results

Mean [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.

Conclusion

This 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.

SUBMITTER: van der Spoel E

PROVIDER: S-EPMC5101217 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

van der Spoel Evie E Roelfsema Ferdinand F Jansen Steffy W SW Akintola Abimbola A AA Ballieux Bart E BE Cobbaert Christa M CM Blauw Gerard J GJ Slagboom P Eline PE Westendorp Rudi G J RG Pijl Hanno H van Heemst Diana D

Frontiers in endocrinology 20161109

<h4>Context</h4>A 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.<h4>Objective</h4>To study 24-h hormone concentration profiles of the HPG axis in men enriched for familial longevity and controls.<h4>Design</h4>We frequently sampled blood over 24 h in 10 healthy middle-aged male offspring of nonagenarian participants from the Leiden Longevity Study together with ...[more]

PMID: 27881971

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Project description:BackgroundWith organismal aging, the hypothalamic-pituitary-gonadal (HPG) activity gradually decreases, resulting in the systemic functional declines of the target tissues including skeletal muscles. Although the HPG axis plays an important role in health span, how the HPG axis systemically prevents functional aging is largely unknown.MethodsWe generated muscle stem cell (MuSC)-specific androgen receptor (Ar) and oestrogen receptor 2 (Esr2) double knockout (dKO) mice and pharmacologically inhibited (Antide) the HPG axis to mimic decreased serum levels of sex steroid hormones in aged mice. After short-term and long-term sex hormone signalling ablation, the MuSCs were functionally analysed, and their aging phenotypes were compared with those of geriatric mice (30-month-old). To investigate pathways associated with sex hormone signalling disruption, RNA sequencing and bioinformatic analyses were performed.ResultsDisrupting the HPG axis results in impaired muscle regeneration [wild-type (WT) vs. dKO, P < 0.0001; Veh vs. Antide, P = 0.004]. The expression of DNA damage marker (in WT = 7.0 ± 1.6%, dKO = 32.5 ± 2.6%, P < 0.01; in Veh = 13.4 ± 4.5%, Antide = 29.7 ± 5.5%, P = 0.028) and senescence-associated β-galactosidase activity (in WT = 3.8 ± 1.2%, dKO = 10.3 ± 1.6%, P < 0.01; in Veh = 2.1 ± 0.4%, Antide = 9.6 ± 0.8%, P = 0.005), as well as the expression levels of senescence-associated genes, p16Ink4a and p21Cip1 , was significantly increased in the MuSCs, indicating that genetic and pharmacological inhibition of the HPG axis recapitulates the progressive aging process of MuSCs. Mechanistically, the ablation of sex hormone signalling reduced the expression of transcription factor EB (Tfeb) and Tfeb target gene in MuSCs, suggesting that sex hormones directly induce the expression of Tfeb, a master regulator of the autophagy-lysosome pathway, and consequently autophagosome clearance. Transduction of the Tfeb in naturally aged MuSCs increased muscle mass [control geriatric MuSC transplanted tibialis anterior (TA) muscle = 34.3 ± 2.9 mg, Tfeb-transducing geriatric MuSC transplanted TA muscle = 44.7 ± 6.7 mg, P = 0.015] and regenerating myofibre size [eMyHC+ tdTomato+ myofibre cross-section area (CSA) in control vs. Tfeb, P = 0.002] after muscle injury.ConclusionsOur data show that the HPG axis systemically controls autophagosome clearance in MuSCs through Tfeb and prevents MuSCs from senescence, suggesting that sustained HPG activity throughout life regulates autophagosome clearance to maintain the quiescence of MuSCs by preventing senescence until advanced age.

Project description:Reproduction is an energetically costly phenomenon. Therefore, to optimize reproductive success, male birds invest enough energetic resources for maintaining well-developed testes. The hypothalamic-pituitary-thyroid (HPT) axis in birds can crosstalk with the hypothalamic-pituitary-gonadal (HPG) axis, thus orchestrating both the reproduction and metabolism. However, until now, how the free-living birds timely optimize both the energy metabolism and reproduction via HPT-axis is not understood. To uncover this physiological mechanism, we investigated the relationships among body mass, testis size, plasma hormones including thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3), metabolites including glucose (Glu), triglyceride (TG), total cholesterol (TC), uric acid (UA), diencephalon mRNA expressions of type 2 (Dio2) and 3 (Dio3) iodothyronine deiodinase enzymes, thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), gonadotropin-releasing hormone I (GnRH-I), and gonadotropin-inhibitory hormone (GnIH) in a male Eurasian tree sparrow (ETS, Passer montanus). We found significantly larger testis size; elevated diencephalon Dio2 and TRH mRNA expressions, plasma T3, and UA levels; and significantly lowered Glu, TG, and TC levels during mating relative to the non-mating stages in male ETSs. However, Dio3, TSH, GnRH-I, and GnIH mRNA expression did not vary with the stage. Furthermore, life-history stage dependent variation in plasma T3 had both direct effects on the available energy substrates and indirect effects on body mass and testis size, indicating a complex regulation of metabolic pathways through the HPT- and HPG-axes. The identified differences and relationships in mRNA expression, plasma T3 and metabolites, and testis size in male ETSs contribute to our understanding how free-living birds adjust their molecular, endocrinal, and biochemical features to orchestrate their reproductive physiology and metabolism for the maintenance of well-developed testes.

Dataset Information

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

Context

Objective

Design

Results

Conclusion

Publications

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

Similar Datasets

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