遗传因素影响寿命。在人类中，年龄≥90岁的人群中似乎存在特别强烈的遗传效应。营养感知基因在细胞韧性方面发挥了重要作用。我们的研究通过对夏威夷瓦胡岛上居住的日裔美国男性进行纵向研究，探究了遗传因素。该队列研究始于1960年代中期，最多的对象现已亡故，最初被称为檀香山心脏计划。我们先前发现了与长寿相关的多种基因的多态性。在对其机制的最新研究中，我们发现长寿基因型减轻了患有心脏代谢疾病（CMD） - 尤其是高血压所带来的死亡风险。对于FOXO3基因，保护性等位基因减轻了高血压、冠心病和糖尿病的风险。对于激酶MAP3K5，它是高血压、冠心病和糖尿病，对于激酶受体PIK3R1，是高血压、冠心病和中风，对于生长激素受体基因（GHR）和血管内皮生长因子受体1基因（FLT1），是消除了高血压导致的更高死亡风险。患有CMD且具有长寿基因型的受试者与没有CMD的男性具有相似的生存能力。没有变异体对抗癌症的死亡风险。我们假设与长寿相关的基因型通过影响细胞内韧性机制来降低死亡风险。在一项蛋白质组学研究中，发现了43个“应激”蛋白及其相关生物途径，它们影响了FOXO3基因型与降低死亡率的关联。我们的重大发现揭示了遗传成分如何影响寿命。©作者（2023）。由美国高血压杂志的牛津大学出版社代表出版。

Genetic factors influence lifespan. In humans, there appears to be a particularly strong genetic effect in those aged ≥ 90 years. An important contribution is nutrient sensing genes which confer cell resilience. Our research has been investigating the genetic factors by longitudinal studies of American men of Japanese descent living on the island of Oahu in Hawaii. This cohort began as the Honolulu Heart Program in the mid-1960s and most subjects are now deceased. We previously discovered various genes containing polymorphisms associated with longevity. In recent investigations of the mechanism involved we found that the longevity genotypes ameliorated the risk of mortality posed by having a cardiometabolic disease (CMD) - most prominently hypertension. For the gene FOXO3 the protective alleles mitigated the risk of hypertension, coronary heart disease (CHD) and diabetes. For the kinase MAP3K5 it was hypertension, CHD and diabetes, for the kinase receptor PIK3R1 hypertension, CHD and stroke, and for the growth hormone receptor gene (GHR) and vascular endothelial growth factor receptor 1 gene (FLT1), it was nullifying the higher mortality risk posed by hypertension. Subjects with a CMD who had a longevity genotype had similar survival as men without CMD. No variant protected against risk of death from cancer. We have postulated that the longevity-associated genotypes reduced mortality risk by effects on intracellular resilience mechanisms. In a proteomics study, 43 "stress" proteins and associated biological pathways were found to influence the association of FOXO3 genotype with reduced mortality. Our landmark findings indicate how heritable genetic components affect longevity.© The Author(s) 2023. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd.