Genes involved in immune response/inflammation, IGF1/insulin pathway and response to oxidative stress play a major role in the genetics of human longevity: the lesson of centenarians

Zinc–gene interaction related to inflammatory/immune response in ageing

“…Genetic analysis of human ageing is mainly approached by searching the genetic basis of susceptibility to major geriatric disorders or the allelic contributions to exceptionally long life span. It is just thanks to these last studies in centenarians populations that several candidate longevity genes or pathways including PON1 [19,130], IGF1/insulin pathway [84,120], elements of lipid metabolism [12], stress response [34] and inflammatory response have been identified [53].…”

“…Genes related to inflammation and stress response, in particular the pro-inflammatory cytokines IL-1, IL-6, TNFalpha, the anti-inflammatory cytokine IL-10, the HSP70 chaperones and the regulators of trace elements homeostasis, metallothioneins (MT), seem particularly relevant taking into account that the same genes are involved in the susceptibility to major geriatric disease/disorders such as diabetes, osteoporosis, osteoarthritis, dementia, cardiovascular diseases and infections [53,107]. Moreover, in the context of human longevity these genes acquire particular weight because, conversely to typical lab organisms usually housed in pathogen-free environments and thus underexposed to pathogens, the humans live in a controlled but not sterile environment [54] responsible for a lifelong antigenic load.…”

“…It has been suggested that IL-6 -174G/C locus variability is capable of modulating on one hand the individual susceptibility to common causes of morbidity and mortality among elderly, on the other hand it may play a crucial role in longevity [53]. Therefore, the genetic variations of this locus of IL-6 gene are fundamental in elderly population in order to better understand the intrinsic causes of the longevity.…”

“…Genetic analysis of human ageing is mainly approached by searching the genetic basis of susceptibility to major geriatric disorders or the allelic contributions to exceptionally long life span. It is just thanks to these last studies in centenarians populations that several candidate longevity genes or pathways including PON1 [19,130], IGF1/insulin pathway [84,120], elements of lipid metabolism [12], stress response [34] and inflammatory response have been identified [53].Genes related to inflammation and stress response, in particular the pro-inflammatory cytokines IL-1, IL-6, TNFalpha, the anti-inflammatory cytokine IL-10, the HSP70 chaperones and the regulators of trace elements homeostasis, metallothioneins (MT), seem particularly relevant taking into account that the same genes are involved in the susceptibility to major geriatric disease/disorders such as …”

The extreme longevity: The state of the art in Italy

“…Vice versa it can be hypothesized that genes neutral or dangerous at younger age can became useful at old or extremely old age. Actually, it is clear that centenarians are part of a special biology in which different tissues and organs could not have reached the same level of senescence, a kind of mosaicism, and their genetics is post-reproductive Franceschi et al, 2005;Salvioli et al, 2006).…”