vB Hjelmborg Jacob, Iachine Ivan, Skytthe Axel, Vaupel James W, McGue Matt, Koskenvuo Markku, Kaprio Jaakko, Pedersen Nancy L, Christensen Kaare
Institute of Public Health, University of Southern Denmark, J. B. Winslovsvej 9 B, 5000, Odense C, Denmark.
Hum Genet. 2006 Apr;119(3):312-21. doi: 10.1007/s00439-006-0144-y. Epub 2006 Feb 4.
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.
人们正在动物模型和人类中大力寻找长寿基因。人类家族研究表明，成年寿命的总体差异中，有相当一部分（约20%-30%）是由遗传因素造成的。但尚不清楚遗传因素对最高龄人群的生存是否变得越来越重要。我们利用1870年至1910年间出生的丹麦、芬兰和瑞典双胞胎这一几乎灭绝的队列（共20502人，随访至2003-2004年），研究遗传因素对人类寿命的影响以及它如何随年龄变化。我们首先根据双胞胎中一方的寿命来估计双胞胎的平均寿命，然后转向活到特定年龄的相对复发风险。男性同卵双胞胎（MZ）的平均寿命，每有一个同卵双胞胎活到60岁以上，其平均寿命就会增加0.39 [95%置信区间（0.28，0.50）] 岁。这一比率显著高于异卵双胞胎（DZ）男性的0.21（0.11，0.30）。女性和男性的比率相似，对于MZ和DZ双胞胎对来说，在60岁之前这些比率可以忽略不计。此外，我们发现有一个同卵双胞胎活到高龄会大幅且显著增加自己活到相同高龄的几率，并且MZ双胞胎的这一几率高于DZ双胞胎。MZ男性活到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，但女性模式随年龄有所变化，这与女性更好的生存率相对应。仅考虑那些活到75岁以上北欧双胞胎时，也会出现类似结果。目前这项基于大量人群的研究显示了遗传因素对人类寿命的影响。虽然估计的遗传影响总体强度与之前的研究一致，但我们发现遗传因素对寿命的影响在60岁之前很小，但此后会增加。这些发现为寻找影响人类长寿的基因提供了支持，尤其是在高龄阶段。
