The Longevity Hormone Klotho is a New Player in the Interacion of the Growth Hormone/Insulin-Like Growth Factor 1 Axis

Pediatr Endocrinol Rev. 2016 Sep;14(1):9-18. doi: 10.17458/PER.2016.RWM.LongevityHormoneKlotho.


Klotho was first discovered as an aging-suppressor gene. Mice that do not express klotho die prematurely with multiple symptoms of aging, several of which are also characteristic of decreased GH/IGF-1 axis activity. Klotho is highly expressed in the brain, the kidney, and parathyroid and pituitary glands, but can also serve as a circulating hormone by its shedding, forming soluble klotho (sKlotho) that can be detected in blood, cerebrospinal fluid and urine. Several lines of evidence suggest an association between klotho levels and activity of the GH/IHG-1 axis: The GH-secreting cells in the anterior pituitary of klotho-deficient mice are hypotrophic; klotho levels are altered in subjects with pathologies of the GH/IGF-1 axis; and accumulating data indicate that klotho is a direct regulator of GH secretion. Thus, klotho seems to be a new player in the intricate regulation of the GH/IGF-1 axis.

Keywords: Acromegaly; Anorexia; Growth hormone deficiency; IGF-1; Klotho.

Publication types

  • Review

MeSH terms

  • Aging / physiology
  • Animals
  • Glucuronidase / chemistry
  • Glucuronidase / genetics
  • Glucuronidase / metabolism*
  • Growth Hormone / metabolism*
  • Humans
  • Insulin-Like Growth Factor I / metabolism*
  • Klotho Proteins
  • Longevity / physiology
  • Mice
  • Mice, Transgenic
  • Signal Transduction / physiology


  • Insulin-Like Growth Factor I
  • Growth Hormone
  • Glucuronidase
  • Klotho Proteins