Lifespan extension conferred by mitogen-activated protein kinase kinase kinase 5 (MAP3K5) longevity-associated gene variation is confined to at-risk men with a cardiometabolic disease.
Lifespan extension conferred by mitogen-activated protein kinase kinase kinase 5 (MAP3K5) longevity-associated gene variation is confined to at-risk men with a cardiometabolic disease.
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DOI：
10.18632/aging.202844
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发表时间：
2021-03-19
期刊：
影响因子：
--
通讯作者：
Willcox BJ
中科院分区：
文献类型：
--
作者：
Morris BJ;Chen R;Donlon TA;Masaki KH;Willcox DC;Allsopp RC;Willcox BJ
激酶信号基因MAP 3 K5的遗传变异与长寿有关。在这里，我们探讨是否长寿协会涉及保护所有个人的死亡率，或仅在个人与衰老相关的疾病。我们在3,516名日本血统的美国老年男性中测试了最强的长寿相关单核苷酸多态性（SNP）rs 2076260与死亡率的相关性。在基线（1991-1993年），2,461人患有糖尿病（n=990），冠心病（CHD; n=724）或高血压（n=1,877），1,055人没有任何这些心脏代谢疾病（CMD）。这些男性从基线随访至2019年12月31日。在主要等位基因纯合子模型中与长寿相关的基因型CC和在杂合子劣势模型中与长寿相关的基因型CC+TT与患有CMD的个体的长寿相关（主要等位基因纯合子模型中的协变量调整风险比[HR]为1.23 [95% CI：1.12-1.35，p=2.5x10-5]，1.11-1.33，p= 1.10 × 10 -5]。对于糖尿病、高血压和CHD，各遗传模型的HR p值分别为0.019、0.00048、0.093和0.0024、0.00040、0.0014。正如预期的那样，没有CMD的男性比有CMD的男性寿命长（p=1.9x10-6）。然而，在没有CMD的男性中，基因型的寿命没有差异（在每个遗传模型中，p分别为0.21和0.86）。总之，我们提出，在患有心脏代谢疾病的个体中，MAP 3 K5中与长寿相关的遗传变异增强了细胞和组织中的弹性机制，以帮助防止CMD引起的心脏代谢应激。因此，具有长寿基因型的CMD男性与所有没有CMD的男性一样长寿。
Genetic variants of the kinase signaling gene MAP3K5 are associated with longevity. Here we explore whether the longevity-association involves protection against mortality in all individuals, or only in individuals with aging-related diseases. We tested the strongest longevity associated single nucleotide polymorphism (SNP), rs2076260, for association with mortality in 3,516 elderly American men of Japanese ancestry. At baseline (1991–1993), 2,461 had either diabetes (n=990), coronary heart disease (CHD; n=724), or hypertension (n=1,877), and 1,055 lacked any of these cardiometabolic diseases (CMDs). The men were followed from baseline until Dec 31, 2019. Longevity-associated genotype CC in a major allele homozygote model, and CC+TT in a heterozygote disadvantage model were associated with longer lifespan in individuals having a CMD (covariate-adjusted hazard ratio [HR] 1.23 [95% CI: 1.12–1.35, p=2.5x10–5] in major allele homozygote model, and 1.22 [95% CI: 1.11–1.33, p=1.10x10–5] in heterozygote disadvantage model). For diabetes, hypertension and CHD, HR p-values were 0.019, 0.00048, 0.093, and 0.0024, 0.00040, 0.0014, in each respective genetic model. As expected, men without a CMD outlived men with a CMD (p=1.9x10–6). There was, however, no difference in lifespan by genotype in men without a CMD (p=0.21 and 0.86, respectively, in each genetic model). In conclusion, we propose that in individuals with a cardiometabolic disease, longevity-associated genetic variation in MAP3K5 enhances resilience mechanisms in cells and tissues to help protect against cardiometabolic stress caused by CMDs. As a result, men with CMD having longevity genotype live as long as all men without a CMD.
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影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
DOI：
10.1016/0021-9681(74)90014-9
发表时间：
1974-01-01
期刊：
JOURNAL OF CHRONIC DISEASES
影响因子：
--
作者：
KAGAN, A;HARRIS, BR;TILLOTSON, J
通讯作者：
TILLOTSON, J
影响因子：
12.7
作者：
DONAHUE, RP;ABBOTT, RD;YANO, K
通讯作者：
YANO, K
DOI：
10.1016/0021-9681(70)90022-6
发表时间：
1970-01-01
期刊：
JOURNAL OF CHRONIC DISEASES
影响因子：
--
作者：
WORTH, RM;KAGAN, A
通讯作者：
KAGAN, A
影响因子：
5
作者：
YANO, K;REED, DM;MCGEE, DL
通讯作者：
MCGEE, DL