Pathways of HPA Axis Resilience in Highly Successful Aging: Evaluation of Basal Plasma Cortisol, ACTH Challenge, and Frailty Burden in Dogs with Exceptional Longevity

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 41-52-HPA Axis & Disease States
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-42
David J. Waters*1, Aimee H Maras2, Huiping Xu3, Seema S Kengeri2 and Emily C Chiang2
1Purdue University, West Lafayette, IN, 2Gerald P. Murphy Cancer Foundation, West Lafayette, IN, 3Indiana University School of Medicine, Indianapolis, IN
An age-related loss of hypothalamic-pituitary-adrenal (HPA) axis resilience can result in hypercortisolism, which has been linked to an array of adverse outcomes including cognitive impairment, progressive cancer growth, and clinical frailty.  To better understand the biological mechanisms and adaptive capacities that contribute to highly successful aging, we studied exceptionally long-lived Rottweiler dogs that, similar to human centenarians, had achieved a duration of longevity that exceeds by more than 30% their breed-specific norm.  We hypothesized that highly successful aging might be associated with a preservation of HPA resilience and life-long avoidance of hypercortisolism.  The HPA axis of 28 canine centenarians was evaluated by determining: basal plasma cortisol, aldosterone, and ACTH concentrations;  post-ACTH challenge plasma cortisol and aldosterone concentrations;  and urine cortisol : creatinine ratio.  Frailty burden was measured using a 13-item frailty index using assessments obtained from interviews with pet owners; one investigator conducted all interviews.  HPA axis evaluation revealed three categories of canine centenarians.  Forty-three percent of dogs had normal basal cortisol with youthful response to ACTH challenge.  Forty percent of dogs had low basal cortisol levels, yet preserved a youthful response to ACTH challenge.  Seventeen percent of dogs showed deterioration of the aldosterone arm of the HPA axis.  None of the canine centenarians had hypercortisolism.  Compared to dogs with normal basal cortisol, dogs with low basal cortisol had lower frailty burden, with strongest difference seen in measures of stamina and mobility (p=.07).  Taken together, our results from canine centenarians suggest that hypercortisolism resulting from impairment of the HPA axis is not an obligate phenotype intrinsic to the aging process.  Further, the discovery of an adaptive, low basal cortisol endophenotype in some of these dogs emphasizes the importance of studies that rely upon challenge, rather than basal measures, to determine how HPA axis resilience contributes to highly successful aging.  Pet dogs should provide a tractable model to study further the relationship between HPA axis resilience and clinical frailty.

Nothing to Disclose: DJW, AHM, HX, SSK, ECC

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