The genetics of human longevity.
Aging is due to a complex interaction of genetic, epigenetic, and environmental factors, but a strong genetic component appears to have an impact on survival to extreme ages. In order to identify "longevity genes" in humans, different strategies are now available. In our laboratory, we performed association studies on a variety of "candidate" polymorphisms in Italian centenarians. Many genes/polymorphisms gave negative results, while others showed a positive association with human longevity and a sometimes-positive association with unsuccessful aging (myocardial infarction, Alzheimer's disease, and type 2 diabetes). Results regarding genes involved in inflammation (IL-1 cluster, IL-6, IL-10, TNF-alpha, TGF-beta, TLR-4, PPARgamma), insulin/IGF-1 signaling pathway and lipid metabolism (apolipoproteins, CETP, PON1), and oxidative stress (p53, p66(shc)) will be described. In addition, a strong role of the interaction between nuclear and mitochondrial genomes (mtDNA haplogroups and the C150T mutation) emerged from our findings. Thus, the genetics of human longevity appears to be quite peculiar in a context where antagonistic pleiotropy can play a major role and genes can have a different biological role at different ages.
Capri
Miriam
M
CIG - Centro Interdipartimentale L. Galvani, University of Bologna, Italy.
Salvioli
Stefano
S
Sevini
Federica
F
Valensin
Silvana
S
Celani
Laura
L
Monti
Daniela
D
Pawelec
Graham
G
De Benedictis
Giovanna
G
Gonos
Efstathios S
ES
Franceschi
Claudio
C
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000502:physiology; D001053:Apolipoproteins / Q000235:genetics; D043303:Aryldialkylphosphatase / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics; D007328:Insulin / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D008136:Longevity / Q000235:genetics* / Q000502:physiology; D005810:Multigene Family; D018384:Oxidative Stress; D047495:PPAR gamma / Q000235:genetics; D011110:Polymorphism, Genetic; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D051197:Toll-Like Receptor 4 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D001053:Apolipoproteins; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D007328:Insulin; D007375:Interleukin-1; D015850:Interleukin-6; D047495:PPAR gamma; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D016753:Interleukin-10; D007334:Insulin-Like Growth Factor I; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human