Insulin-like growth factors and aging: lessons from Laron syndrome

Front Endocrinol (Lausanne). 2023 Oct 24:14:1291812. doi: 10.3389/fendo.2023.1291812. eCollection 2023.

Abstract

The growth hormone (GH)-insulin-like growth factor-1 (IGF1) signaling pathway emerged in recent years as a key determinant of aging and longevity. Disruption of this network in different animal species, including flies, nematodes and mouse, was consistently associated with an extended lifespan. Epidemiological analyses have shown that patients with Laron syndrome (LS), the best-characterized disease under the umbrella of the congenital IGF1 deficiencies, seem to be protected from cancer. While aging and cancer, as a rule, are considered diametrically opposite processes, modern lines of evidence reinforce the notion that aging and cancer might, as a matter of fact, be regarded as divergent manifestations of identical biochemical and cellular underlying processes. While the effect of individual mutations on lifespan and health span is very difficult to assess, genome-wide screenings identified a number of differentially represented aging- and longevity-associated genes in patients with LS. The present review summarizes recent data that emerged from comprehensive analyses of LS patients and portrays a number of previously unrecognized targets for GH-IGF1 action. Our article sheds light on complex aging and longevity processes, with a particular emphasis on the role of the GH-IGF1 network in these mechanisms.

Keywords: IGF1 receptor; Laron syndrome; aging; growth hormone (GH); insulin-like growth factor-1 (IGF1).

Publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aging / genetics
  • Animals
  • Growth Hormone
  • Human Growth Hormone* / genetics
  • Humans
  • Laron Syndrome* / genetics
  • Longevity / genetics
  • Mice
  • Neoplasms* / metabolism

Substances

  • Growth Hormone
  • Human Growth Hormone

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Work in the laboratory of HW was supported by grants from the Israel Science Foundation (1403/14), US-Israel Binational Science Foundation (201282), and the Israel Cancer Association (20181082).