Abstract
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. To study 24-h hormone concentration profiles of the HPG axis in men enriched for familial longevity and controls. 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. 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. 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.
Highlights
Over the last decades, several conserved mechanisms have been identified that associate with longevity in both animal models and humans
We found that growth hormone (GH) secretion was diminished and tightly controlled in offspring compared to controls [15]
We did not observe significant differences in 24-h secretion of HPG axis parameters and their regulation between male subjects enriched for familial longevity compared to controls
Summary
Several conserved mechanisms have been identified that associate with longevity in both animal models and humans. The common function of these evolutionarily conserved systems is to enable the organism to adequately respond to changes in the environment in order to maintain homeostasis This is achieved by adapting the balance between growth, development, and reproduction versus maintenance and repair [1]. The hypothalamus regulates homeostasis via neural and endocrine pathways These latter comprise the hypothalamic–pituitary–thyroid (HPT) axis, the hypothalamic–pituitary–growth hormone (GH) axis, the hypothalamic–pituitary–adrenal (HPA) axis, the hypothalamic–pituitary–prolactin (PRL) axis, and the hypothalamic–pituitary–gonadal (HPG) axis. Likewise, fasting was observed to suppress the HPG, HPT, GH, and PRL axes and to stimulate the HPA axis in healthy men [3] While these adaptive responses are clearly beneficial for short-term survival, their long-term health consequences may vary depending on the type and severity of the stress. In humans, decreased reproduction was found to associate with exceptional human longevity in both men and women [6]
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