Abstract

Background: Dietary intervention and genetic alterations in geneencoding proteins involved in nutrient-sensing pathways can modulatelifespan, influencing longevity. It depends on under/over-expression ofregulatory molecules that lead to different expression of homeostaticgenes. Insulin/IGF-1 pathway was associated with longevity and lifespanmodulation in model organisms. In humans, a key molecule in thispathway is FOXO3A that acts as a TF on homeostatic genes in responseto decreased signaling increasing life span. Interestingly, other genes thatincrease lifespan interact with FOXO3A such as SIRT1, which modulatesthe oxidative stress response.Methods: We used meta-analytical and candidate-gene approaches toinvestigate the association of SNPs encoding proteins involved inInsulin/IGF-1 pathway with ageing and longevity.Results: Our study confirmed previous results related to the associationbetween FOXO3A, IGF-1R, KLOTHO and longevity. No association wasreported between IGF-1 and SIRT1 although all IGF-1 SNPs could affectits serum levels, known to modulate ageing and longevity. Moreover, weshowed a new association between SHIP2 SNPs and longevity.Conclusions: Our results showed that specific SNPs of IGF-1R,FOXO3A, SHIP2 and KLOTHO influence ageing and longevity in differentethnic populations and that FOXO3A could be the most relevant gene inlifespan extension, particularly in males. Moreover, it could be speculatedthat a reduction of insulin signaling may decrease the activation of NF-kBslowing down inflammatory gene transcription. Thus, the intervention onageing and longevity should be based both on nutrient-sensing andinflammatory pathways. The first simple step could be represented by theadherence to the Mediterranean diet with low glycaemic index and lowanimal proteins.
Lingua originaleEnglish
pagine (da-a)12-12
Numero di pagine1
RivistaTHE AMERICAN JOURNAL OF PATHOLOGY
Volume184
Stato di pubblicazionePublished - 2014

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