晚育:年长的男人能生健康的孩子吗?

晚育:年长的男人能生健康的孩子吗?

An 86-year-old man recently walked into my office – and wanted to achieve pregnancy using his sperm, donor eggs and a gestational surrogate. He preferred to transfer the embryos to two surrogates because he was well aware of the risks related to twins; however, he had no doubt his sperm could create healthy children at his age. "Charlie Chaplin was a father at the age of 73," he remarked. "Why can't I be a father?" After my patient left, a quick online search revealed that, indeed, the world's most famous older fathers include Mick Jagger and Charlie Chaplin.It raises the questions: When does paternity end, and can older men have healthy children?

最近，一位86岁的老人走进我的办公室，他想用自己的精子、捐赠的卵子和代孕妈妈来怀孕。他更愿意将胚胎移植给两个代孕者，因为他很清楚双胞胎的风险;然而，他毫不怀疑他的精子能在他这个年龄生出健康的孩子。他说:“查理·卓别林是一位73岁的父亲。“为什么我不能做一个父亲?”在我的病人离开后，我快速上网查询显示，事实上，世界上最著名的年长父亲包括米克·贾格尔(Mick Jagger)和查理·卓别林(Charlie Chaplin)。这就提出了一个问题:亲子关系什么时候结束?年龄较大的男性能否拥有健康的孩子?

The average age of a father in the U.S. is 30. Most of the prospective fathers who come to my fertility clinic are around age 40. In modern times, we delay maternity and paternity. At age 43, a woman is told 90% of her embryos will be genetically abnormal, while a 68-year-old man is told everything is OK on his side because he has a normal semen analysis. But what happens to the DNA of the sperm as men age?

美国父亲的平均年龄为30岁。大多数来我生育诊所的准爸爸都在40岁左右。在现代，我们推迟了生育和亲子关系。43岁的女性被告知90%的胚胎在基因上是不正常的，而68岁的男性则被告知一切正常，因为他的精液分析正常。但是随着男性年龄的增长，精子的DNA会发生什么变化呢?

DNA stands for deoxyribonucleic acid, and it's the familiar "double helix" molecule forming the building blocks of every living organism. In our body, DNA is tightly coiled up into chromosomes, and each chromosome contains a specific number of genes. In every cell in our body, we have 23 pairs of chromosomes.

DNA代表脱氧核糖核酸，它是一种常见的“双螺旋”分子，构成了每一个生物体的组成部分。在我们的身体里，DNA紧紧地缠绕成染色体，每条染色体都含有特定数量的基因。在我们身体的每个细胞中，我们有23对染色体。

An example of this that many people are familiar with is Down syndrome, which means the individual was born with three copies of chromosome 21 – creating more than 23 chromosomes. Interestingly, there is no paternal age effect with Down syndrome, yet there's twice the increased risk of miscarriage with advanced paternity.

很多人都熟悉的一个例子是唐氏综合症，这意味着一个人出生时携带着3个21号染色体副本——产生了23条以上的染色体。有趣的是，父亲的年龄对唐氏综合症没有影响，但父亲的年龄越长，流产的风险就会增加一倍。

Additionally, as men age, there's a higher chance of their children developing single gene disorders such as achondroplasia and osteogenesis imperfecta. Achondroplasia is a genetic disorder that arises from a point mutation in the FGFR3 gene and results in dwarfism.

此外，随着男性年龄的增长，他们的孩子更有可能患上单基因疾病，如软骨发育不全和成骨不全。软骨发育不全是由FGFR3基因点突变引起的一种遗传性疾病，可导致侏儒症。

Population geneticist, James Crow, claimed: "The greatest mutational health hazard to the human genome is fertile older males." Researchers sequenced the whole genome of 78 Icelandic parent-offspring trios of children with autism and found it is the age of the father that is the dominant factor in determining the number of new mutations in the child.

人口遗传学家詹姆斯·克劳(James Crow)声称:“对人类基因组最大的突变健康危害是生育能力较强的老年男性。”研究人员对78名冰岛自闭症儿童的父母和子女进行了全基因组测序，发现父亲的年龄是决定孩子新突变数量的主要因素。

The study was published in the journal Nature and showed paternal contribution of two additional mutations per year. The sperm could be the source of evolution .

这项研究发表在《自然》(Nature)杂志上，显示父亲每年会增加两种基因突变。精子可能是进化的来源。

Nevertheless, there are social benefits and detriments of older paternity. Later age at parenthood is also associated with a more emotionally and financially stable family environment. On the contrary, there is a risk of the father dying before the child becomes an adult.

然而，年长的父亲既有社会益处，也有坏处。晚年为人父母也与更稳定的情感和财务状况有关。相反，在孩子成年之前，有父亲死亡的风险。

In summary, "advanced paternal age" is generally used to describe men age 40 and older at the time of conception. However, there is no uniformly accepted definition. The effects of reproductive aging on sperm DNA are more gradual and complex. Also, we don’t have diagnostic tests to identify when a man's sperm might be damaged due to aging. And there's not enough data on the genetic effects related to freezing and thawing sperm to recommend young men to bank their sperm, either. Perhaps this is something to consider in the future.

总而言之，“高龄父亲”一般用于描述40岁以上男性在受孕时的年龄。然而，并没有统一的定义。生殖老化对精子DNA的影响更为缓慢和复杂。此外，我们还没有诊断测试来确定男性的精子何时可能因衰老而受损。而且，关于冷冻和解冻精子的遗传效应，也没有足够的数据来建议年轻男性将精子储存起来。也许这是将来要考虑的事情。