Integrity of hypothalamic–pituitary-testicular axis in exceptional longevity

Sandra Aleksic, Dimpi Desai, Kenny Ye, Sally Duran, Tina Gao, Jill Crandall, Gil Atzmon, Nir Barzilai, Sofiya Milman

Research output: Contribution to journalArticlepeer-review


Hypothalamic integrity increasingly is being recognized as a marker of healthy longevity in rodent models. Insight into hypothalamic function in humans with exceptional longevity can be gained via investigation of the hypothalamic–pituitary-testicular (HPT) axis in men with exceptional longevity. This study aimed to characterize the HPT axis function, defined by levels of testosterone (T) and luteinizing hormone (LH), in 84 Ashkenazi Jewish men aged 90–106 years. We found that 94% of men exhibited preserved hypothalamic–pituitary function, as evidenced by either normal testosterone and LH levels (25%) or an appropriate rise in LH in response to aging-related primary testicular dysfunction (69%), a hormone pattern mirroring female menopause. Total T level was not associated with metabolic parameters or survival. These results demonstrate a high prevalence of testicular dysfunction with preserved hypothalamic–pituitary function in men with exceptional longevity. Thus, the role of hypothalamic integrity and HPT axis in healthy aging warrants further investigation.

Original languageEnglish
JournalAging Cell
StateAccepted/In press - 2022

Bibliographical note

Funding Information:
We acknowledge Dr. Peter Snyder for guidance on data analysis and interpretation; Dr. Paul R. Marantz for review of the manuscript; Dr. Hubert Vesper for information on the CDC‐HoSt program standards and Dr. Tom Fiers for sharing tools to calculate FT. This work was funded by NIH/NCATS Einstein‐Montefiore CTSA UL1TR002556 (KY, SA), KL2TR002258 (SA), the Glenn Foundation for Medical Research (NB, SM), NIH/NIA R01AG044829 (NB), K23AG051148 (SM) and AFAR (SM).

Publisher Copyright:
© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.


  • centenarians
  • endocrinology
  • human
  • hypothalamus
  • longevity
  • testosterone

ASJC Scopus subject areas

  • Aging
  • Cell Biology


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