title: Liver-derived IGF-I regulates mean life span in mice.
abstract: BACKGROUND
  Transgenic mice with low levels of global insulin-like growth factor-I (IGF-I) throughout their life span, including pre- and postnatal development, have increased longevity. This study investigated whether specific deficiency of liver-derived, endocrine IGF-I is of importance for life span.
  
  
  RESULTS
  Serum IGF-I was reduced by approximately 80% in mice with adult, liver-specific IGF-I inactivation (LI-IGF-I(-/-) mice), and body weight decreased due to reduced body fat. The mean life span of LI-IGF-I(-/-) mice (n = 84) increased 10% vs. control mice (n = 137) (Cox's test, p<0.01), mainly due to increased life span (16%) of female mice [LI-IGF-I(-/-) mice (n = 31): 26.7±1.1 vs. control (n = 67): 23.0±0.7 months, p<0.001]. Male LI-IGF-I(-/-) mice showed only a tendency for increased longevity (p = 0.10). Energy expenditure, measured as oxygen consumption during and after submaximal exercise, was increased in the LI-IGF-I(-/-) mice. Moreover, microarray and RT-PCR analyses showed consistent regulation of three genes (heat shock protein 1A and 1B and connective tissue growth factor) in several body organs in the LI-IGF-I(-/-) mice.
  
  
  CONCLUSIONS
  Adult inactivation of liver-derived, endocrine IGF-I resulted in moderately increased mean life span. Body weight and body fat decreased in LI-IGF-I(-/-) mice, possibly due to increased energy expenditure during exercise. Genes earlier reported to modulate stress response and collagen aging showed consistent regulation, providing mechanisms that could underlie the increased mean life span in the LI-IGF-I(-/-) mice.
authors.affiliation: Department of Internal Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. johan.svensson@medic.gu.se
authors.forename: Johan
authors.initials: J
authors.lastname: Svensson
authors.forename: Klara
authors.initials: K
authors.lastname: Sjögren
authors.forename: Jenny
authors.initials: J
authors.lastname: Fäldt
authors.forename: Niklas
authors.initials: N
authors.lastname: Andersson
authors.forename: Olle
authors.initials: O
authors.lastname: Isaksson
authors.forename: John-Olov
authors.initials: JO
authors.lastname: Jansson
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
mesh_terms: D000818:Animals; D001823:Body Composition / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D004435:Eating / Q000235:genetics; D005260:Female; D005298:Fertility / Q000235:genetics; D005786:Gene Expression Regulation; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008136:Longevity / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D010101:Oxygen Consumption / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007334:Insulin-Like Growth Factor I