ROLE of IGF-1 System in the Modulation of Longevity: Controversies and New Insights From a Centenarians' Perspective

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2019 Feb 19

PMID 30774624

Citations 63

Authors

Giovanni Vitale

Giuseppe Pellegrino

Maria Vollery

Leo J Hofland

Affiliations

Soon will be listed here.

Abstract

Human aging is currently defined as a physiological decline of biological functions in the body with a continual adaptation to internal and external damaging. The endocrine system plays a major role in orchestrating cellular interactions, metabolism, growth, and aging. Several studies from worms to mice showed that downregulated activity of the GH/IGF-1/insulin pathway could be beneficial for the extension of human life span, whereas results are contradictory in humans. In the present review, we discuss the potential role of the IGF-1 system in modulation of longevity, hypothesizing that the endocrine and metabolic adaptation observed in centenarians and in mammals during caloric restriction may be a physiological strategy for extending lifespan through a slower cell growing/metabolism, a better physiologic reserve capacity, a shift of cellular metabolism from cell proliferation to repair activities and a decrease in accumulation of senescent cells. Therefore, understanding of the link between IGF-1/insulin system and longevity may have future clinical applications in promoting healthy aging and in Rehabilitation Medicine.

Citing Articles

Changes in insulin, adiponectin and lipid concentrations with age are associated with frailty and reduced quality of life in dogs.

McKenzie B, Peloquin M, Graves J, Chen F, Tovar A, Carttar T Sci Rep. 2025; 15(1):5380.

PMID: 39948141 PMC: 11825863. DOI: 10.1038/s41598-025-89923-z.

New insights into methods to measure biological age: a literature review.

Mathur A, Taurin S, Alshammary S Front Aging. 2025; 5:1395649.

PMID: 39743988 PMC: 11688636. DOI: 10.3389/fragi.2024.1395649.

Crosstalk between adipogenesis and aging: role of polyphenols in combating adipogenic-associated aging.

Al-Regaiey K Immun Ageing. 2024; 21(1):76.

PMID: 39511615 PMC: 11542427. DOI: 10.1186/s12979-024-00481-w.

Is age more than a number? Accounting for adult development and aging in the study of psychoneuroimmunology, stress, and health.

Wilson S Compr Psychoneuroendocrinol. 2024; 20:100266.

PMID: 39445313 PMC: 11497474. DOI: 10.1016/j.cpnec.2024.100266.

The IGF System and Aging.

Conover C, Oxvig C Endocr Rev. 2024; 46(2):214-223.

PMID: 39418083 PMC: 11894535. DOI: 10.1210/endrev/bnae029.

References

Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen A, Skinhoj P, Pedersen B . A high plasma concentration of TNF-alpha is associated with dementia in centenarians. J Gerontol A Biol Sci Med Sci. 1999; 54(7):M357-64. DOI: 10.1093/gerona/54.7.m357. View

Paolisso G, Manzella D, Barbieri M, Rizzo M, Gambardella A, Varricchio M . Baseline heart rate variability in healthy centenarians: differences compared with aged subjects (>75 years old). Clin Sci (Lond). 1999; 97(5):579-84. View

Paolisso G, Tagliamonte M, Rizzo M, Carella C, Gambardella A, Barbieri M . Low plasma insulin-like growth factor-1 concentrations predict worsening of insulin-mediated glucose uptake in older people. J Am Geriatr Soc. 1999; 47(11):1312-8. DOI: 10.1111/j.1532-5415.1999.tb07431.x. View

Migliaccio E, Giorgio M, Mele S, Pelicci G, Reboldi P, Pandolfi P . The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature. 1999; 402(6759):309-13. DOI: 10.1038/46311. View

Coschigano K, Clemmons D, Bellush L, Kopchick J . Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology. 2000; 141(7):2608-13. DOI: 10.1210/endo.141.7.7586. View

Franceschi C, Valensin S, Bonafe M, Paolisso G, Yashin A, Monti D . The network and the remodeling theories of aging: historical background and new perspectives. Exp Gerontol. 2000; 35(6-7):879-96. DOI: 10.1016/s0531-5565(00)00172-8. View

Gerli R, Monti D, Bistoni O, Mazzone A, Peri G, Cossarizza A . Chemokines, sTNF-Rs and sCD30 serum levels in healthy aged people and centenarians. Mech Ageing Dev. 2001; 121(1-3):37-46. DOI: 10.1016/s0047-6374(00)00195-0. View

Arai Y, Hirose N, Yamamura K, Shimizu K, Takayama M, Ebihara Y . Serum insulin-like growth factor-1 in centenarians: implications of IGF-1 as a rapid turnover protein. J Gerontol A Biol Sci Med Sci. 2001; 56(2):M79-82. DOI: 10.1093/gerona/56.2.m79. View

Clancy D, Gems D, Harshman L, Oldham S, Stocker H, Hafen E . Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science. 2001; 292(5514):104-6. DOI: 10.1126/science.1057991. View

10.

Tatar M, Kopelman A, Epstein D, Tu M, Yin C, Garofalo R . A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science. 2001; 292(5514):107-10. DOI: 10.1126/science.1057987. View

11.

Flurkey K, Papaconstantinou J, Miller R, Harrison D . Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc Natl Acad Sci U S A. 2001; 98(12):6736-41. PMC: 34422. DOI: 10.1073/pnas.111158898. View

12.

Bartke A, Wright J, Mattison J, Ingram D, Miller R, Roth G . Extending the lifespan of long-lived mice. Nature. 2001; 414(6862):412. DOI: 10.1038/35106646. View

13.

Paolisso G, Barbieri M, Rizzo M, Carella C, Rotondi M, Bonafe M . Low insulin resistance and preserved beta-cell function contribute to human longevity but are not associated with TH-INS genes. Exp Gerontol. 2001; 37(1):149-56. DOI: 10.1016/s0531-5565(01)00148-6. View

14.

Berrigan D, Perkins S, Haines D, Hursting S . Adult-onset calorie restriction and fasting delay spontaneous tumorigenesis in p53-deficient mice. Carcinogenesis. 2002; 23(5):817-22. DOI: 10.1093/carcin/23.5.817. View

15.

Holzenberger M, Dupont J, Ducos B, Leneuve P, Geloen A, Even P . IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature. 2002; 421(6919):182-7. DOI: 10.1038/nature01298. View

16.

Gangemi S, Basile G, Merendino R, Minciullo P, Novick D, Rubinstein M . Increased circulating Interleukin-18 levels in centenarians with no signs of vascular disease: another paradox of longevity?. Exp Gerontol. 2003; 38(6):669-72. DOI: 10.1016/s0531-5565(03)00061-5. View

17.

Bonafe M, Barbieri M, Marchegiani F, Olivieri F, Ragno E, Giampieri C . Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control. J Clin Endocrinol Metab. 2003; 88(7):3299-304. DOI: 10.1210/jc.2002-021810. View

18.

Coschigano K, Holland A, Riders M, List E, Flyvbjerg A, Kopchick J . Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span. Endocrinology. 2003; 144(9):3799-810. DOI: 10.1210/en.2003-0374. View

19.

Libina N, Berman J, Kenyon C . Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan. Cell. 2003; 115(4):489-502. DOI: 10.1016/s0092-8674(03)00889-4. View

20.

van Heemst D, Beekman M, Mooijaart S, Heijmans B, Brandt B, Zwaan B . Reduced insulin/IGF-1 signalling and human longevity. Aging Cell. 2005; 4(2):79-85. DOI: 10.1111/j.1474-9728.2005.00148.x. View