A polymorphic variant of the insulin-like growth factor 1 (IGF-1) receptor correlates with male longevity in the Italian population: a genetic study and evaluation of circulating IGF-1 from the "Treviso Longeva (TRELONG)" study.
BACKGROUND
An attenuation of the insulin-like growth factor 1 (IGF-1) signaling has been associated with elongation of the lifespan in simple metazoan organisms and in rodents. In humans, IGF-1 level has an age-related modulation with a lower concentration in the elderly, depending on hormonal and genetic factors affecting the IGF-1 receptor gene (IGF-1R).


METHODS
In an elderly population from North-eastern Italy (n = 668 subjects, age range 70-106 years) we investigated the IGF-1R polymorphism G3174A (rs2229765) and the plasma concentration of free IGF-1. Frequency distributions were compared using chi2-test "Goodness of Fit" test, and means were compared by one-way analysis of variance (ANOVA); multiple regression analysis was performed using JMP7 for SAS software (SAS Institute, USA). The limit of significance for genetic and biochemical comparison was set at alpha = 0.05.


RESULTS
Males showed an age-related increase in the A-allele of rs2229765 and a change in the plasma level of IGF-1, which dropped significantly after 85 years of age (85+ group). In the male 85+ group, A/A homozygous subjects had the lowest plasma IGF-1 level. We found no clear correlation between rs2229765 genotype and IGF-1 in the females.


CONCLUSIONS
These findings confirm the importance of the rs2229765 minor allele as a genetic predisposing factor for longevity in Italy where a sex-specific pattern for IGF-1 attenuation with ageing was found.
Albani
Diego
D
Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Italy. albani@marionegri.it
Batelli
Sara
S
Polito
Letizia
L
Vittori
Angelica
A
Pesaresi
Marzia
M
Gajo
Giovanni Battista
GB
De Angeli
Sergio
S
Zanardo
Andrea
A
Gallucci
Maurizio
M
Forloni
Gianluigi
G
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000235:genetics; D000483:Alleles; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism*; D007558:Italy; D008136:Longevity / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D017526:Receptor, IGF Type 1 / Q000097:blood* / Q000235:genetics*; D012737:Sex Factors; D011795:Surveys and Questionnaires
D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1