TY - JOUR
T1 - Human longevity within an evolutionary perspective
T2 - The peculiar paradigm of a post-reproductive genetics
AU - Capri, Miriam
AU - Salvioli, Stefano
AU - Monti, Daniela
AU - Caruso, Calogero
AU - Candore, Giuseppina
AU - Vasto, Sonya
AU - Olivieri, Fabiola
AU - Marchegiani, Francesca
AU - Sansoni, Paolo
AU - Baggio, Giovannella
AU - Mari, Daniela
AU - Passarino, Giuseppe
AU - De Benedictis, Giovanna
AU - Franceschi, Claudio
PY - 2008/2
Y1 - 2008/2
N2 - The data we collected on the genetics of human longevity, mostly resulting from studies on centenarians, indicate that: (1) centenarians and long-living sibpairs are a good choice for the study of human longevity, because they represent an extreme phenotype, i.e., the survival tail of the population who escaped neonatal mortality, pre-antibiotic era illnesses, and fatal outcomes of age-related complex diseases. (2) The model of centenarians is not simply an additional model with respect to well-studied organisms, and the study of humans has revealed characteristics of ageing and longevity (geographical and sex differences, role of antigenic load and inflammation, role of mtDNA variants) which did not emerge from studies in laboratory model systems and organisms. (3) All the phenotypic characteristics of nonagenarians and centenarians fit the hypothesis that ageing is a remodelling process where the body of survivors progressively adapts to internal and external damaging agents they are exposed to during several decades, largely unpredicted by evolution. (4) Such a remodelling process, which can be considered a Darwinian process occurring at the somatic level within the framework of the evolutionary constraints, established by evolution for Homo sapiens as a species, may explain why the same gene polymorphism can have different (beneficial or detrimental) effects at different ages. (5) Geographic and demographic evidence suggest that longevity can be achieved by different combinations of genes, environment, and chance quantitatively and qualitatively different in many geographic areas, and that population-specific genetic factors, play a role on the longevity trait. (6) The concomitant and integrated use of new in silico and high throughput strategies will greatly accelerate the identification of new longevity genes in humans.
AB - The data we collected on the genetics of human longevity, mostly resulting from studies on centenarians, indicate that: (1) centenarians and long-living sibpairs are a good choice for the study of human longevity, because they represent an extreme phenotype, i.e., the survival tail of the population who escaped neonatal mortality, pre-antibiotic era illnesses, and fatal outcomes of age-related complex diseases. (2) The model of centenarians is not simply an additional model with respect to well-studied organisms, and the study of humans has revealed characteristics of ageing and longevity (geographical and sex differences, role of antigenic load and inflammation, role of mtDNA variants) which did not emerge from studies in laboratory model systems and organisms. (3) All the phenotypic characteristics of nonagenarians and centenarians fit the hypothesis that ageing is a remodelling process where the body of survivors progressively adapts to internal and external damaging agents they are exposed to during several decades, largely unpredicted by evolution. (4) Such a remodelling process, which can be considered a Darwinian process occurring at the somatic level within the framework of the evolutionary constraints, established by evolution for Homo sapiens as a species, may explain why the same gene polymorphism can have different (beneficial or detrimental) effects at different ages. (5) Geographic and demographic evidence suggest that longevity can be achieved by different combinations of genes, environment, and chance quantitatively and qualitatively different in many geographic areas, and that population-specific genetic factors, play a role on the longevity trait. (6) The concomitant and integrated use of new in silico and high throughput strategies will greatly accelerate the identification of new longevity genes in humans.
KW - Antagonistic pleiotropy
KW - Centenarians
KW - Genetics
KW - Longevity
UR - http://www.scopus.com/inward/record.url?scp=38149093342&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38149093342&partnerID=8YFLogxK
U2 - 10.1016/j.exger.2007.06.004
DO - 10.1016/j.exger.2007.06.004
M3 - Article
C2 - 17692487
AN - SCOPUS:38149093342
VL - 43
SP - 53
EP - 60
JO - Experimental Gerontology
JF - Experimental Gerontology
SN - 0531-5565
IS - 2
ER -