Effects of FOXO genotypes on longevity: a biodemographic analysis.
Based on data from 760 centenarians and 1060 middle-age controls (all Han Chinese), this article contributes biodemographic insights and syntheses concerning the magnitude of effects of the FOXO genotypes on longevity. We also estimate independent and joint effects of the genotypes of FOXO1A and FOXO3A genes on long-term survival, considering carrying or not-carrying the minor allele of the single-nucleotide polymorphism of another relevant gene. We found substantial gender differences in the independent effects; positive effects of FOXO3A and negative effects of FOXO1A largely compensate each other if one carries both, although FOXO3A has a stronger impact. Ten-year follow-up cohort analysis shows that at very advanced ages 92-110, adjusted for various confounders, positive effects of FOXO3A on survival remain statistically significant, but no significant effects of FOXO1A alone; G × G interactions between FOXO1A-209 and FOXO3A-310 or FOXO3A-292 decrease survival likelihood by 32%-36% (p < .05); G × E interactions between FOXO1A-209 and regular exercise increase survival likelihood by 31%-32% (p < .05).
Zeng
Yi
Y
Center for the Study of Aging and Human Development, Medical School of Duke University, Durham, NC 27710, USA. zengyi68@gmail.com
Cheng
Lingguo
L
Chen
Huashuai
H
Cao
Huiqing
H
Hauser
Elizabeth R
ER
Liu
Yuzhi
Y
Xiao
Zhenyu
Z
Tan
Qihua
Q
Tian
Xiao-Li
XL
Vaupel
James W
JW
D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D016013:Likelihood Functions; D008136:Longevity / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011336:Probability; D016016:Proportional Hazards Models; D012737:Sex Factors; D016019:Survival Analysis
C085126:FOXO1 protein, human; C499517:FOXO3 protein, human; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors