Genetic influence on human lifespan and longevity
Genetic influence on human lifespan and longevity
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DOI：
10.1007/s00439-006-0144-y
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发表时间：
2006-04-01
期刊：
影响因子：
5.3
通讯作者：
Christensen, K
中科院分区：
文献类型：
--
作者：
Hjelmborg, JV;Iachine, I;Christensen, K
在动物模型和人类中都有一个对长寿基因的密集搜索。人类家族研究表明，成人寿命的总体变化中有少量（约20-30%）是由遗传因素造成的。但目前尚不清楚遗传因素是否对老年人的生存变得越来越重要。我们研究了基因对人类寿命的影响，以及它如何随着年龄的变化而变化，使用了1870年至1910年出生的几乎灭绝的丹麦，芬兰和瑞典双胞胎队列，包括20，502人，直到2003-2004年。我们首先通过双胞胎的寿命来估计双胞胎的平均寿命，然后转向存活到给定年龄的相对复发风险。男性同卵（MZ）双胞胎的平均寿命增加0.39 [95% CI（0.28，0.50）]年，他的双胞胎每生存超过60岁。该比率显著大于双合子（DZ）男性的比率0.21（0.11，0.30）。女性和男性的发病率相似，在60岁之前，MZ和DZ对的发病率可以忽略不计。此外，我们发现，有一个共同的双胞胎活到老年的机会大大增加，达到相同的老年，这种机会是更高的MZ比DZ双胞胎。MZ男性达到92岁的相对复发风险为4.8（2.2，7.5），显著高于DZ男性的1.8（0.10，3.4）。女性和男性的模式非常相似，但随着年龄的增长，女性模式发生了变化，这与女性生存率较高相对应。当只考虑那些存活超过75岁的北欧双胞胎时，也会出现类似的结果。目前的大规模人群研究表明，基因对人类寿命的影响。虽然估计的遗传影响的总体强度与以前的研究是一致的，但我们发现，遗传对寿命的影响在60岁之前是最小的，但此后会增加。这些发现为寻找影响人类寿命的基因提供了支持，特别是在老年。
There is an intense search for longevity genes in both animal models and humans. Human family studies have indicated that a modest amount of the overall variation in adult lifespan (approximately 20-30%) is accounted for by genetic factors. But it is not known if genetic factors become increasingly important for survival at the oldest ages. We study the genetic influence on human lifespan and how it varies with age using the almost extinct cohorts of Danish, Finnish and Swedish twins born between 1870 and 1910 comprising 20,502 individuals followed until 2003-2004. We first estimate mean lifespan of twins by lifespan of co-twin and then turn to the relative recurrence risk of surviving to a given age. Mean lifespan for male monozygotic (MZ) twins increases 0.39 [95% CI (0.28, 0.50)] years for every year his co-twin survives past age 60 years. This rate is significantly greater than the rate of 0.21 (0.11, 0.30) for dizygotic (DZ) males. Females and males have similar rates and these are negligible before age 60 for both MZ and DZ pairs. We moreover find that having a co-twin surviving to old ages substantially and significantly increases the chance of reaching the same old age and this chance is higher for MZ than for DZ twins. The relative recurrence risk of reaching age 92 is 4.8 (2.2, 7.5) for MZ males, which is significantly greater than the 1.8 (0.10, 3.4) for DZ males. The patterns for females and males are very similar, but with a shift of the female pattern with age that corresponds to the better female survival. Similar results arise when considering only those Nordic twins that survived past 75 years of age. The present large population based study shows genetic influence on human lifespan. While the estimated overall strength of genetic influence is compatible with previous studies, we find that genetic influences on lifespan are minimal prior to age 60 but increase thereafter. These findings provide a support for the search for genes affecting longevity in humans, especially at advanced ages.