PMID- 18710818 OWN - NLM STAT- MEDLINE DCOM- 20090619 LR - 20211020 IS - 1532-2238 (Electronic) IS - 1096-6374 (Print) IS - 1096-6374 (Linking) VI - 18 IP - 6 DP - 2008 Dec TI - Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models. PG - 455-71 LID - 10.1016/j.ghir.2008.05.005 [doi] AB - Animal models are fundamentally important in our quest to understand the genetic, epigenetic, and environmental factors that contribute to human aging. In comparison to humans, relatively short-lived mammals are useful models as they allow for rapid assessment of both genetic manipulation and environmental intervention as related to longevity. These models also allow for the study of clinically relevant pathologies as a function of aging. Data associated with more distant species offers additional insight and critical consideration of the basic physiological processes and molecular mechanisms that influence lifespan. Consistently, two interventions, caloric restriction and repression of the growth hormone (GH)/insulin-like growth factor-1/insulin axis, have been shown to increase lifespan in both invertebrates and vertebrate animal model systems. Caloric restriction (CR) is a nutrition intervention that robustly extends lifespan whether it is started early or later in life. Likewise, genes involved in the GH/IGF-1 signaling pathways can lengthen lifespan in vertebrates and invertebrates, implying evolutionary conservation of the molecular mechanisms. Specifically, insulin and insulin-like growth factor-1 (IGF-1)-like signaling and its downstream intracellular signaling molecules have been shown to be associated with lifespan in fruit flies and nematodes. More recently, mammalian models with reduced growth hormone (GH) and/or IGF-1 signaling have also been shown to have extended lifespans as compared to control siblings. Importantly, this research has also shown that these genetic alterations can keep the animals healthy and disease-free for longer periods and can alleviate specific age-related pathologies similar to what is observed for CR individuals. Thus, these mutations may not only extend lifespan but may also improve healthspan, the general health and quality of life of an organism as it ages. In this review, we will provide an overview of how the manipulation of the GH/IGF axis influences lifespan, highlight the invertebrate and vertebrate animal models with altered lifespan due to modifications to the GH/IGF-1 signaling cascade or homologous pathways, and discuss the basic phenotypic characteristics and healthspan of these models. FAU - Berryman, Darlene E AU - Berryman DE AD - School of Human and Consumer Sciences, College of Health and Human Services, Ohio University, Athens, OH 45701, United States. FAU - Christiansen, Jens Sandahl AU - Christiansen JS FAU - Johannsson, Gudmundur AU - Johannsson G FAU - Thorner, Michael O AU - Thorner MO FAU - Kopchick, John J AU - Kopchick JJ LA - eng GR - K01-DK064905/DK/NIDDK NIH HHS/United States GR - R01 CA099904/CA/NCI NIH HHS/United States GR - R01 AG019899/AG/NIA NIH HHS/United States GR - CA099904/CA/NCI NIH HHS/United States GR - K01 DK064905/DK/NIDDK NIH HHS/United States GR - AG19899/AG/NIA NIH HHS/United States GR - R15 DK075436/DK/NIDDK NIH HHS/United States GR - DK075436/DK/NIDDK NIH HHS/United States GR - R15 DK075436-01A1/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20080816 PL - Scotland TA - Growth Horm IGF Res JT - Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society JID - 9814320 RN - 67763-96-6 (Insulin-Like Growth Factor I) RN - 9002-72-6 (Growth Hormone) SB - IM MH - Aging/*physiology MH - Animals MH - Caloric Restriction MH - Growth Hormone/genetics/*physiology MH - Humans MH - Insulin-Like Growth Factor I/genetics/*physiology MH - Longevity/*physiology MH - Models, Animal MH - Signal Transduction PMC - PMC2631405 MID - NIHMS84804 EDAT- 2008/08/20 09:00 MHDA- 2009/06/20 09:00 PMCR- 2009/12/01 CRDT- 2008/08/20 09:00 PHST- 2008/04/24 00:00 [received] PHST- 2008/05/02 00:00 [accepted] PHST- 2008/08/20 09:00 [pubmed] PHST- 2009/06/20 09:00 [medline] PHST- 2008/08/20 09:00 [entrez] PHST- 2009/12/01 00:00 [pmc-release] AID - S1096-6374(08)00088-9 [pii] AID - 10.1016/j.ghir.2008.05.005 [doi] PST - ppublish SO - Growth Horm IGF Res. 2008 Dec;18(6):455-71. doi: 10.1016/j.ghir.2008.05.005. Epub 2008 Aug 16.