FOXO3 longevity genotype mitigates the increased mortality risk in men with a cardiometabolic disease.
Aging (Albany NY)
; 12(23): 23509-23524, 2020 12 01.
Article
em En
| MEDLINE
| ID: mdl-33260156
ABSTRACT
FOXO3 is a prominent longevity gene. To date, no-one has examined whether longevity-associated FOXO3 genetic variants protect against mortality in all individuals, or only in those with aging-related diseases. We therefore tested longevity-associated FOXO3 single nucleotide polymorphisms in a haplotype block for association with mortality in 3,584 elderly American men of Japanese ancestry, 2,512 with and 1,072 without a cardiometabolic disease (CMD). At baseline (1991-1993), 1,010 CMD subjects had diabetes, 1,919 had hypertension, and 738 had coronary heart disease (CHD). Follow-up until Dec 31, 2019 found that in CMD-affected individuals, longevity-associated alleles of FOXO3 were associated with significantly longer lifespan haplotype hazard ratio 0.81 (95% CI 0.72-0.91; diabetes 0.77, hypertension 0.82, CHD 0.83). Overall, men with a CMD had higher mortality than men without a CMD (P=6x10-7). However, those men with a CMD who had the FOXO3 longevity genotype had similar survival as men without a CMD. In men without a CMD there was no association of longevity-associated alleles of FOXO3 with lifespan. Our study provides novel insights into the basis for the long-established role of FOXO3 as a longevity gene. We suggest that the FOXO3 longevity genotype increases lifespan only in at-risk individuals by protection against cardiometabolic stress.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença das Coronárias
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Polimorfismo de Nucleotídeo Único
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Síndrome Metabólica
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Diabetes Mellitus Tipo 2
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Proteína Forkhead Box O3
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Hipertensão
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Longevidade
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Observational_studies
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Prevalence_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Aged80
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Humans
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Male
País como assunto:
America do norte
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Asia
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article