title: 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.
abstract: In this paper, we review data of recent literature on the distribution in centenarians of candidate germ-line polymorphisms that likely affect the individual chance to reach the extreme limit of human life. On the basis of previous observations on the immunology, endocrinology and cellular biology of centenarians we focused on genes that regulate immune responses and inflammation (IL-6, IL-1 cluster, IL-10), genes involved in the insulin/IGF-I signalling pathway and genes that counteract oxidative stress (PON1). On the whole, data indicate that polymorphisms of these genes likely contribute to human longevity, in accord with observations emerging from a variety of animal models, and suggest that a common core of master genes and metabolic pathways are responsible for aging and longevity across animal species. Moreover, in the concern of our plan to discover new genetic factors related to longevity, we explored the possibility to by-pass the need of an a-priori choice of candidate genes, extending the search to genes and genomic regions of still unknown function. Alu sequences may be considered as good markers of highly variable and potentially unstable loci in functionally important genomic regions. We extensively screened Alu-rich genomic sites and found a new genomic region associated with longevity.
authors.affiliation: Italian National Research Center on Aging, Ancona, Italy. b.molecolare@inrca.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.forename: Fabiola
authors.initials: F
authors.lastname: Olivieri
authors.forename: Francesca
authors.initials: F
authors.lastname: Marchegiani
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cardelli
authors.forename: Luca
authors.initials: L
authors.lastname: Cavallone
authors.forename: Miriam
authors.initials: M
authors.lastname: Capri
authors.forename: Stefano
authors.initials: S
authors.lastname: Salvioli
authors.forename: Silvana
authors.initials: S
authors.lastname: Valensin
authors.forename: Giovanna
authors.initials: G
authors.lastname: De Benedictis
authors.forename: Angelo
authors.initials: A
authors.lastname: Di Iorio
authors.forename: Calogero
authors.initials: C
authors.lastname: Caruso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paolisso
authors.forename: Daniela
authors.initials: D
authors.lastname: Monti
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D043303:Aryldialkylphosphatase / Q000235:genetics; D005838:Genotype; D006801:Humans; D007109:Immunity / Q000235:genetics*; D007249:Inflammation / Q000235:genetics*; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008136:Longevity; D008954:Models, Biological; D005810:Multigene Family; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D015398:Signal Transduction
chemical_list: D007328:Insulin; D007375:Interleukin-1; D015850:Interleukin-6; D016753:Interleukin-10; D007334:Insulin-Like Growth Factor I; D043303:Aryldialkylphosphatase