TY - JOUR
T1 - The genetics of human longevity
AU - Capri, Miriam
AU - Salvioli, Stefano
AU - Sevini, Federica
AU - Valensin, Silvana
AU - Celani, Laura
AU - Monti, Daniela
AU - Pawelec, Graham
AU - De Benedictis, Giovanna
AU - Gonos, Efstathios S.
AU - Franceschi, Claudio
PY - 2006/5
Y1 - 2006/5
N2 - 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-α, TGF-β, TLR-4, PPARγ), insulin/IGF-1 signaling pathway and lipid metabolism (apolipoproteins, CETP, PON1), and oxidative stress (p53, p66shc) 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.
AB - 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-α, TGF-β, TLR-4, PPARγ), insulin/IGF-1 signaling pathway and lipid metabolism (apolipoproteins, CETP, PON1), and oxidative stress (p53, p66shc) 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.
KW - Apolipoproteins
KW - CETP
KW - IL-1 cluster
KW - IL-10
KW - IL-6
KW - insulin/IGF-1
KW - Longevity genes
KW - p53, p66
KW - PON1
KW - PPARγ
KW - TGF-β
KW - TLR-4
KW - TNF-α
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U2 - 10.1196/annals.1354.033
DO - 10.1196/annals.1354.033
M3 - Article
C2 - 16803995
AN - SCOPUS:33744542074
VL - 1067
SP - 252
EP - 263
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
SN - 0077-8923
IS - 1
ER -