The paradox of the insulin/IGF-1 signaling pathway in longevity

Marielisa Rincon, Radhika Muzumdar, Gil Atzmon, Nir Barzilai

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Ageing may be controlled by a genetic-hormonal system that may have originated from a very early common ancestor. One of the pathways that has been implicated in ageing is the insulin/insulin-like growth factor (IGF-1) signaling, which is involved in many functions that are necessary for metabolism, growth, and fertility in animal models like flies, nematodes and mammalians. While disruption of the insulin/IGF-1 receptor in nematodes and flies increases lifespan significantly, mammals with genetic or acquired defects in insulin signaling pathway are at risk for age-related diseases and increased mortality. This contradiction can be explained by the acquisition of more complicated metabolic pathways in mammalians over evolution. Mammals have insulin/IGF-1 receptors in many organs, but their functions are opposite if they are located in the central nervous system or in the periphery; whereas lower species have insulin/IGF-1 receptors signaling mainly through the nervous system. Furthermore, mammalians have different and very specific receptors for insulin and IGF-1, with distinct pathways and diverse functions. Striking evidence suggests that decreased IGF-1 levels and signaling during early development, but not the insulin signaling may modulate longevity in many species. Thus, paradoxical outcomes follow the decrease of insulin and/or IGF-1 signal pathway in invertebrates and in mammals, prolonging life in the former and shortening it in the latter. In this review we focus on the downstream cascade of events in the insulin and IGF-1 signaling to identify specific pathways that are relevant to human longevity.

Original languageEnglish (US)
Pages (from-to)397-403
Number of pages7
JournalMechanisms of Ageing and Development
Volume125
Issue number6
DOIs
StatePublished - Jun 2004

Fingerprint

Insulin-Like Growth Factor I
Insulin
IGF Type 1 Receptor
Mammals
Neurology
Diptera
Aging of materials
Insulin Receptor
Somatomedins
Metabolism
Invertebrates
Metabolic Networks and Pathways
Nervous System
Animals
Fertility
Signal Transduction
Central Nervous System
Animal Models
Defects
Mortality

Keywords

  • IGF-1
  • Insulin
  • Longevity

ASJC Scopus subject areas

  • Aging
  • Biochemistry
  • Developmental Biology
  • Developmental Neuroscience

Cite this

The paradox of the insulin/IGF-1 signaling pathway in longevity. / Rincon, Marielisa; Muzumdar, Radhika; Atzmon, Gil; Barzilai, Nir.

In: Mechanisms of Ageing and Development, Vol. 125, No. 6, 06.2004, p. 397-403.

Research output: Contribution to journalArticle

Rincon, Marielisa ; Muzumdar, Radhika ; Atzmon, Gil ; Barzilai, Nir. / The paradox of the insulin/IGF-1 signaling pathway in longevity. In: Mechanisms of Ageing and Development. 2004 ; Vol. 125, No. 6. pp. 397-403.
@article{ed1117ade9ec4c0a9fa7532b07f58218,
title = "The paradox of the insulin/IGF-1 signaling pathway in longevity",
abstract = "Ageing may be controlled by a genetic-hormonal system that may have originated from a very early common ancestor. One of the pathways that has been implicated in ageing is the insulin/insulin-like growth factor (IGF-1) signaling, which is involved in many functions that are necessary for metabolism, growth, and fertility in animal models like flies, nematodes and mammalians. While disruption of the insulin/IGF-1 receptor in nematodes and flies increases lifespan significantly, mammals with genetic or acquired defects in insulin signaling pathway are at risk for age-related diseases and increased mortality. This contradiction can be explained by the acquisition of more complicated metabolic pathways in mammalians over evolution. Mammals have insulin/IGF-1 receptors in many organs, but their functions are opposite if they are located in the central nervous system or in the periphery; whereas lower species have insulin/IGF-1 receptors signaling mainly through the nervous system. Furthermore, mammalians have different and very specific receptors for insulin and IGF-1, with distinct pathways and diverse functions. Striking evidence suggests that decreased IGF-1 levels and signaling during early development, but not the insulin signaling may modulate longevity in many species. Thus, paradoxical outcomes follow the decrease of insulin and/or IGF-1 signal pathway in invertebrates and in mammals, prolonging life in the former and shortening it in the latter. In this review we focus on the downstream cascade of events in the insulin and IGF-1 signaling to identify specific pathways that are relevant to human longevity.",
keywords = "IGF-1, Insulin, Longevity",
author = "Marielisa Rincon and Radhika Muzumdar and Gil Atzmon and Nir Barzilai",
year = "2004",
month = "6",
doi = "10.1016/j.mad.2004.03.006",
language = "English (US)",
volume = "125",
pages = "397--403",
journal = "Mechanisms of Ageing and Development",
issn = "0047-6374",
publisher = "Elsevier Ireland Ltd",
number = "6",

}

TY - JOUR

T1 - The paradox of the insulin/IGF-1 signaling pathway in longevity

AU - Rincon, Marielisa

AU - Muzumdar, Radhika

AU - Atzmon, Gil

AU - Barzilai, Nir

PY - 2004/6

Y1 - 2004/6

N2 - Ageing may be controlled by a genetic-hormonal system that may have originated from a very early common ancestor. One of the pathways that has been implicated in ageing is the insulin/insulin-like growth factor (IGF-1) signaling, which is involved in many functions that are necessary for metabolism, growth, and fertility in animal models like flies, nematodes and mammalians. While disruption of the insulin/IGF-1 receptor in nematodes and flies increases lifespan significantly, mammals with genetic or acquired defects in insulin signaling pathway are at risk for age-related diseases and increased mortality. This contradiction can be explained by the acquisition of more complicated metabolic pathways in mammalians over evolution. Mammals have insulin/IGF-1 receptors in many organs, but their functions are opposite if they are located in the central nervous system or in the periphery; whereas lower species have insulin/IGF-1 receptors signaling mainly through the nervous system. Furthermore, mammalians have different and very specific receptors for insulin and IGF-1, with distinct pathways and diverse functions. Striking evidence suggests that decreased IGF-1 levels and signaling during early development, but not the insulin signaling may modulate longevity in many species. Thus, paradoxical outcomes follow the decrease of insulin and/or IGF-1 signal pathway in invertebrates and in mammals, prolonging life in the former and shortening it in the latter. In this review we focus on the downstream cascade of events in the insulin and IGF-1 signaling to identify specific pathways that are relevant to human longevity.

AB - Ageing may be controlled by a genetic-hormonal system that may have originated from a very early common ancestor. One of the pathways that has been implicated in ageing is the insulin/insulin-like growth factor (IGF-1) signaling, which is involved in many functions that are necessary for metabolism, growth, and fertility in animal models like flies, nematodes and mammalians. While disruption of the insulin/IGF-1 receptor in nematodes and flies increases lifespan significantly, mammals with genetic or acquired defects in insulin signaling pathway are at risk for age-related diseases and increased mortality. This contradiction can be explained by the acquisition of more complicated metabolic pathways in mammalians over evolution. Mammals have insulin/IGF-1 receptors in many organs, but their functions are opposite if they are located in the central nervous system or in the periphery; whereas lower species have insulin/IGF-1 receptors signaling mainly through the nervous system. Furthermore, mammalians have different and very specific receptors for insulin and IGF-1, with distinct pathways and diverse functions. Striking evidence suggests that decreased IGF-1 levels and signaling during early development, but not the insulin signaling may modulate longevity in many species. Thus, paradoxical outcomes follow the decrease of insulin and/or IGF-1 signal pathway in invertebrates and in mammals, prolonging life in the former and shortening it in the latter. In this review we focus on the downstream cascade of events in the insulin and IGF-1 signaling to identify specific pathways that are relevant to human longevity.

KW - IGF-1

KW - Insulin

KW - Longevity

UR - http://www.scopus.com/inward/record.url?scp=2942536602&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2942536602&partnerID=8YFLogxK

U2 - 10.1016/j.mad.2004.03.006

DO - 10.1016/j.mad.2004.03.006

M3 - Article

C2 - 15272501

AN - SCOPUS:2942536602

VL - 125

SP - 397

EP - 403

JO - Mechanisms of Ageing and Development

JF - Mechanisms of Ageing and Development

SN - 0047-6374

IS - 6

ER -