title: Characterization of the Hypothalamic-Pituitary-Adrenal-Axis in Familial Longevity under Resting Conditions.
abstract: OBJECTIVE
  The hypothalamic-pituitary-adrenal (HPA)-axis is the most important neuro-endocrine stress response system of our body which is of critical importance for survival. Disturbances in HPA-axis activity have been associated with adverse metabolic and cognitive changes. Humans enriched for longevity have less metabolic and cognitive disturbances and therefore diminished activity of the HPA axis may be a potential candidate mechanism underlying healthy familial longevity. Here, we compared 24-h plasma ACTH and serum cortisol concentration profiles and different aspects of the regulation of the HPA-axis in offspring from long-lived siblings, who are enriched for familial longevity and age-matched controls.
  
  
  METHODS
  Case-control study within the Leiden Longevity study cohort consisting of 20 middle-aged offspring of nonagenarian siblings (offspring) together with 18 partners (controls).
  
  
  METHODS
  During 24 h, venous blood was sampled every 10 minutes for determination of circulatory ACTH and cortisol concentrations. Deconvolution analysis, cross approximate entropy analysis and ACTH-cortisol-dose response modeling were used to assess, respectively, ACTH and cortisol secretion parameters, feedforward and feedback synchrony and adrenal gland ACTH responsivity.
  
  
  RESULTS
  Mean (95% Confidence Interval) basal ACTH secretion was higher in male offspring compared to male controls (645 (324-1286) ngl/L/24 h versus 240 (120-477) ng/L/24 h, P = 0.05). Other ACTH and cortisol secretion parameters did not differ between offspring and controls. In addition, no significant differences in feedforward and feedback synchrony and adrenal gland ACTH responsivity were observed between groups.
  
  
  CONCLUSIONS
  These results suggest that familial longevity is not associated with major differences in HPA-axis activity under resting conditions, although modest, sex-specific differences may exist between groups that might be clinically relevant.
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Steffy W
authors.initials: SW
authors.lastname: Jansen
authors.affiliation: Department of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Roelfsema
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Abimbola A
authors.initials: AA
authors.lastname: Akintola
authors.affiliation: Developmental Psychology (ADAPT-lab), University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Brain and Cognition (ABC), University of Amsterdam, Amsterdam, The Netherlands; Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Nicole Y
authors.initials: NY
authors.lastname: Oei
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Christa M
authors.initials: CM
authors.lastname: Cobbaert
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Bart E
authors.initials: BE
authors.lastname: Ballieux
authors.affiliation: Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands; Leiden Institute for Brain and Cognition (LIBC), Leiden University, Leiden, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van der Grond
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands; Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Rudi G
authors.initials: RG
authors.lastname: Westendorp
authors.affiliation: Department of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Hanno
authors.initials: H
authors.lastname: Pijl
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Diana
authors.initials: D
authors.lastname: van Heemst
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008136:Longevity; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000378:metabolism*
chemical_list: D000324:Adrenocorticotropic Hormone; D006442:Glycated Hemoglobin; D006854:Hydrocortisone; C517652:hemoglobin A1c protein, human