publication . Article . 2015

Insulin, Aging, and the Brain: Mechanisms and Implications

Akintola, Abimbola A.; van Heemst, Diana;
Open Access English
  • Published: 01 Feb 2015 Journal: Frontiers in Endocrinology, volume 6 (issn: 1664-2392, eissn: 1664-2392, Copyright policy)
  • Publisher: Frontiers Media S.A.
Abstract
There is now an impressive body of literature implicating insulin and insulin signaling in successful aging and longevity. New information from in vivo and in vitro studies concerning insulin and insulin receptors has extended our understanding of the physiological role of insulin in the brain. However, the relevance of these to aging and longevity remains to be elucidated. Here, we review advances in our understanding of the physiological role of insulin in the brain, how insulin gets into the brain, and its relevance to aging and longevity. Furthermore, we examine possible future therapeutic applications and implications of insulin in the context of available ...
Subjects
free text keywords: insulin receptors, accelerated aging, Review Article, insulin, inflammation, RC648-665, longevity, longevity., delayed aging, Diseases of the endocrine glands. Clinical endocrinology, brain, Endocrinology
Funded by
EC| HUMAN
Project
HUMAN
Health and the Understanding of Metabolism, Aging and Nutrition
  • Funder: European Commission (EC)
  • Project Code: 602757
  • Funding stream: FP7 | SP1 | HEALTH
174 references, page 1 of 12

1 Holzenberger M Dupont J Ducos B Leneuve P Geloen A Even PC IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature (2003) 421(6919):182–7.10.1038/nature01298 12483226 [OpenAIRE] [PubMed] [DOI]

2 Iser WB Gami MS Wolkow CA. Insulin signaling in Caenorhabditis elegans regulates both endocrine-like and cell-autonomous outputs. Dev Biol (2007) 303(2):434–47.10.1016/j.ydbio.2006.04.467 17257591 [OpenAIRE] [PubMed] [DOI]

3 Bartke A Chandrashekar V Dominici F Turyn D Kinney B Steger R Insulin-like growth factor 1 (IGF-1) and aging: controversies and new insights. Biogerontology (2003) 4(1):1–8.10.1023/A:1022448532248 12652183 [PubMed] [DOI]

4 Bluher M Kahn BB Kahn CR. Extended longevity in mice lacking the insulin receptor in adipose tissue. Science (2003) 299(5606):572–4.10.1126/science.1078223 12543978 [PubMed] [DOI]

5 Fulop T Larbi A Douziech N. Insulin rec eptor and ageing. Pathol Biol (2003) 51(10):574–80.10.1016/j.patbio.2003.09.007 14622948 [PubMed] [DOI]

6 Fulop T Jr Nagy JT Worum I Foris G Mudri K Varga P Glucose intolerance and insulin resistance with aging – studies on insulin receptors and post-receptor events. Arch Gerontol Geriatr (1987) 6(2):107–15.10.1016/0167-4943(87)90003-3 3307664 [PubMed] [DOI]

7 Rozing MP Westendorp RG Frolich M de Craen AJ Beekman M Heijmans BT Human insulin/IGF-1 and familial longevity at middle age. Aging (2009) 1(8):714–22.20157552 [OpenAIRE] [PubMed]

8 Wijsman CA Rozing MP Streefland TC le Cessie S Mooijaart SP Slagboom PE Familial longevity is marked by enhanced insulin sensitivity. Aging Cell (2011) 10(1):114–21.10.1111/j.1474-9726.2010.00650.x 21070591 [PubMed] [DOI]

9 Barbieri M Gambardella A Paolisso G Varricchio M Metabolic aspects of the extreme longevity. Exp Gerontol (2008) 43(2):74–8 10.1016/j.exger.2007.06.003 17697759 [PubMed] [DOI]

10 Barbieri M Rizzo MR Manzella D Grella R Ragno E Carbonella M Glucose regulation and oxidative stress in healthy centenarians. Exp Gerontol (2003) 38(1–2):137–43.10.1016/S0531-5565(02)00153-5 12543271 [PubMed] [DOI]

11 Paolisso G Gambardella A Ammendola S D’Amore A Balbi V Varricchio M Glucose tolerance and insulin action in healthy centenarians. Am J Physiol (1996) 270(5 Pt 1):E890–4.8967479 [PubMed]

12 Duarte AI Moreira PI Oliveira CR. Insulin in central nervous system: more than just a peripheral hormone. J Aging Res (2012) 2012:384017.10.1155/2012/384017 22500228 [OpenAIRE] [PubMed] [DOI]

13 Schwartz MW Seeley RJ Tschop MH Woods SC Morton GJ Myers MG Cooperation between brain and islet in glucose homeostasis and diabetes. Nature (2013) 503(7474):59–66.10.1038/nature12709 24201279 [OpenAIRE] [PubMed] [DOI]

14 Gerozissis K. Brain insulin: regulation, mechanisms of action and functions. Cell Mol Neurobiol (2003) 23(1):1–25.10.1023/A:1025021529347 12701881 [OpenAIRE] [PubMed] [DOI]

15 Derakhshan F Toth C Insulin and the brain. Curr Diabetes Rev (2013) 9(2):102–16 10.2174/1573399811309020002 23231032 [PubMed] [DOI]

174 references, page 1 of 12
Abstract
There is now an impressive body of literature implicating insulin and insulin signaling in successful aging and longevity. New information from in vivo and in vitro studies concerning insulin and insulin receptors has extended our understanding of the physiological role of insulin in the brain. However, the relevance of these to aging and longevity remains to be elucidated. Here, we review advances in our understanding of the physiological role of insulin in the brain, how insulin gets into the brain, and its relevance to aging and longevity. Furthermore, we examine possible future therapeutic applications and implications of insulin in the context of available ...
Subjects
free text keywords: insulin receptors, accelerated aging, Review Article, insulin, inflammation, RC648-665, longevity, longevity., delayed aging, Diseases of the endocrine glands. Clinical endocrinology, brain, Endocrinology
Funded by
EC| HUMAN
Project
HUMAN
Health and the Understanding of Metabolism, Aging and Nutrition
  • Funder: European Commission (EC)
  • Project Code: 602757
  • Funding stream: FP7 | SP1 | HEALTH
174 references, page 1 of 12

1 Holzenberger M Dupont J Ducos B Leneuve P Geloen A Even PC IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature (2003) 421(6919):182–7.10.1038/nature01298 12483226 [OpenAIRE] [PubMed] [DOI]

2 Iser WB Gami MS Wolkow CA. Insulin signaling in Caenorhabditis elegans regulates both endocrine-like and cell-autonomous outputs. Dev Biol (2007) 303(2):434–47.10.1016/j.ydbio.2006.04.467 17257591 [OpenAIRE] [PubMed] [DOI]

3 Bartke A Chandrashekar V Dominici F Turyn D Kinney B Steger R Insulin-like growth factor 1 (IGF-1) and aging: controversies and new insights. Biogerontology (2003) 4(1):1–8.10.1023/A:1022448532248 12652183 [PubMed] [DOI]

4 Bluher M Kahn BB Kahn CR. Extended longevity in mice lacking the insulin receptor in adipose tissue. Science (2003) 299(5606):572–4.10.1126/science.1078223 12543978 [PubMed] [DOI]

5 Fulop T Larbi A Douziech N. Insulin rec eptor and ageing. Pathol Biol (2003) 51(10):574–80.10.1016/j.patbio.2003.09.007 14622948 [PubMed] [DOI]

6 Fulop T Jr Nagy JT Worum I Foris G Mudri K Varga P Glucose intolerance and insulin resistance with aging – studies on insulin receptors and post-receptor events. Arch Gerontol Geriatr (1987) 6(2):107–15.10.1016/0167-4943(87)90003-3 3307664 [PubMed] [DOI]

7 Rozing MP Westendorp RG Frolich M de Craen AJ Beekman M Heijmans BT Human insulin/IGF-1 and familial longevity at middle age. Aging (2009) 1(8):714–22.20157552 [OpenAIRE] [PubMed]

8 Wijsman CA Rozing MP Streefland TC le Cessie S Mooijaart SP Slagboom PE Familial longevity is marked by enhanced insulin sensitivity. Aging Cell (2011) 10(1):114–21.10.1111/j.1474-9726.2010.00650.x 21070591 [PubMed] [DOI]

9 Barbieri M Gambardella A Paolisso G Varricchio M Metabolic aspects of the extreme longevity. Exp Gerontol (2008) 43(2):74–8 10.1016/j.exger.2007.06.003 17697759 [PubMed] [DOI]

10 Barbieri M Rizzo MR Manzella D Grella R Ragno E Carbonella M Glucose regulation and oxidative stress in healthy centenarians. Exp Gerontol (2003) 38(1–2):137–43.10.1016/S0531-5565(02)00153-5 12543271 [PubMed] [DOI]

11 Paolisso G Gambardella A Ammendola S D’Amore A Balbi V Varricchio M Glucose tolerance and insulin action in healthy centenarians. Am J Physiol (1996) 270(5 Pt 1):E890–4.8967479 [PubMed]

12 Duarte AI Moreira PI Oliveira CR. Insulin in central nervous system: more than just a peripheral hormone. J Aging Res (2012) 2012:384017.10.1155/2012/384017 22500228 [OpenAIRE] [PubMed] [DOI]

13 Schwartz MW Seeley RJ Tschop MH Woods SC Morton GJ Myers MG Cooperation between brain and islet in glucose homeostasis and diabetes. Nature (2013) 503(7474):59–66.10.1038/nature12709 24201279 [OpenAIRE] [PubMed] [DOI]

14 Gerozissis K. Brain insulin: regulation, mechanisms of action and functions. Cell Mol Neurobiol (2003) 23(1):1–25.10.1023/A:1025021529347 12701881 [OpenAIRE] [PubMed] [DOI]

15 Derakhshan F Toth C Insulin and the brain. Curr Diabetes Rev (2013) 9(2):102–16 10.2174/1573399811309020002 23231032 [PubMed] [DOI]

174 references, page 1 of 12
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publication . Article . 2015

Insulin, Aging, and the Brain: Mechanisms and Implications

Akintola, Abimbola A.; van Heemst, Diana;