SHIP2:A ‘‘NEW’’ Insulin Pathway Target for Aging Research

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7 Citations (Scopus)


Strong evidence suggests that systemic inflammation and central adiposity contribute to and perpetuate metabolicsyndrome. All of these alterations predispose individuals to type 2 diabetes mellitus (T2DM), cardiovasculardisease, as well as Alzheimer’s disease (AD), all characterized by chronic inflammatory status. On theother hand, extensive abnormalities in insulin and insulin-like growth factor I (IGF-I) and IGF-II signalingmechanisms in brains with AD have been demonstrated, suggesting that AD could be a third form of diabetes.The Src homology domain-containing inositol 5-phosphatase 2 (SHIP2) has an important role in the insulinpathway because its over-expression causes impairment of insulin/IGF-1 signaling. Because some singlenucleotidepolymorphisms (SNP) of the gene encoding SHIP2 were significantly associated in T2DM patientswith metabolic syndrome and some related conditions, we decided to conduct a case–control study on this gene,analyzing AD and T2DM subjects as cases and young, old, and centenarians as controls. Our results suggest aputative correlation between the the rs144989913 SNP and aging, both successful and unsuccessful, rather thanage-related diseases. Because this SNP is an insertion/deletion of 28 bp, it might cause an alteration in SHIP2expression. It is noteworthy that SHIP2 has been demonstrated to be a potent negative regulator of insulinsignaling and insulin sensitivity. Many studies demonstrated the association of the insulin/IGF1 pathway withaging and longevity, so it is tempting to speculate that the found association with SHIP2 and aging mightdepend on its effect on the insulin/IGF-1 pathway
Original languageEnglish
Pages (from-to)221-225
Number of pages5
JournalRejuvenation Research
Publication statusPublished - 2014

All Science Journal Classification (ASJC) codes

  • Ageing
  • Geriatrics and Gerontology


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