Offspring's leukocyte telomere length, paternal age, and telomere elongation in sperm.
Offspring's leukocyte telomere length, paternal age, and telomere elongation in sperm.
复制标题
后代的白细胞端粒长度，父亲时代和精子中的端粒伸长率。
DOI：
10.1371/journal.pgen.0040037
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发表时间：
2008-02
期刊：
影响因子：
4.5
通讯作者：
Aviv, Abraham
中科院分区：
文献类型：
--
作者：
Kimura, Masayuki;Cherkas, Lynn F.;Kato, Bernet S.;Demissie, Serkalem;Hjelmborg, Jacob B.;Brimacombe, Michael;Cupples, Adrienne;Hunkin, Janice L.;Gardner, Jefferey P.;Lu, Xiaobin;Cao, Xiaojian;Sastrasinh, Malinee;Province, Michael A.;Hunt, Steven C.;Christensen, Kaare;Levy, Daniel;Spector, Tim D.;Aviv, Abraham
白细胞端粒长度（LTL）是一个复杂的遗传性状。它随着年龄的增长而缩短，并与许多与衰老有关的疾病有关。最近的研究发现，年长父亲的后代有更长的LTL。我们在4个不同的队列中探讨了父亲年龄与后代LTL之间的关系。此外，我们研究了潜在的原因，父亲的年龄对后代的LTL描绘端粒参数在精子供体。我们通过Southern印迹法测量了年龄在18-94岁之间的高加索男性和女性（n=3365）的LTL，这些患者来自Frachearts心脏研究的后代（Frachearts后代）、NHLBI家族心脏研究（NHLBI-心脏）、丹麦老龄双胞胎纵向研究（丹麦双胞胎）和英国成人双胞胎登记处（英国双胞胎）。使用Southern印迹，Q-FISH和flow-FISH，我们还测量了46名年轻（<30岁）和老年（>50岁）供体精子的端粒参数。父亲的年龄有一个独立的影响，表示由一个较长的LTL在男性的Fragmentary Offspring和丹麦双胞胎，男性和女性的NHLBI的心脏，和女性的英国双胞胎。每增加一年的父亲年龄，在后代的LTL增加的幅度从一半到两倍以上的年度损耗LTL随着年龄的增长。此外，精子端粒长度分析与老年男性中出现的端粒延长的精子子集是一致的。父亲的年龄对后代的LTL产生了相当大的影响，这种现象可能与老年男性精子中的端粒延长有关。这种影响的含义值得详细研究。白细胞端粒长度随着年龄的增长而变短，显然是人类衰老的生物标志物和长寿的预测者。白细胞端粒长度是可遗传的，女性比男性长，患有与衰老有关的疾病，特别是心血管疾病的人相对较短。本研究发现，在四个不同的人群中，成年后代的白细胞端粒长度与后代出生时的父亲年龄呈正相关。对年轻（<30岁）和老年（>50岁）捐献者精子中端粒的分析显示，老年捐献者中出现了一个端粒延长的精子子集。这种神秘的、年龄依赖性的精子端粒长度延长背后的机制尚不清楚，但可能与表观遗传因素或生殖系干细胞亚群的存活有关，对衰老有弹性。也不知道年长的父亲是如何赋予后代白细胞中更长的端粒的。父亲年龄对白细胞端粒长度的潜在影响，以及可以想象的，与年龄有关的疾病和后代的寿命是相关的，因为老年父亲的后代在社会中所占的比例越来越大。
Leukocyte telomere length (LTL) is a complex genetic trait. It shortens with age and is associated with a host of aging-related disorders. Recent studies have observed that offspring of older fathers have longer LTLs. We explored the relation between paternal age and offspring's LTLs in 4 different cohorts. Moreover, we examined the potential cause of the paternal age on offspring's LTL by delineating telomere parameters in sperm donors. We measured LTL by Southern blots in Caucasian men and women (n=3365), aged 18–94 years, from the Offspring of the Framingham Heart Study (Framingham Offspring), the NHLBI Family Heart Study (NHLBI-Heart), the Longitudinal Study of Aging Danish Twins (Danish Twins), and the UK Adult Twin Registry (UK Twins). Using Southern blots, Q-FISH, and flow-FISH, we also measured telomere parameters in sperm from 46 young (<30 years) and older (>50 years) donors. Paternal age had an independent effect, expressed by a longer LTL in males of the Framingham Offspring and Danish Twins, males and females of the NHLBI-Heart, and females of UK Twins. For every additional year of paternal age, LTL in offspring increased at a magnitude ranging from half to more than twice of the annual attrition in LTL with age. Moreover, sperm telomere length analyses were compatible with the emergence in older men of a subset of sperm with elongated telomeres. Paternal age exerts a considerable effect on the offspring's LTL, a phenomenon which might relate to telomere elongation in sperm from older men. The implications of this effect deserve detailed study. Leukocyte telomere length becomes shorter with age and is apparently a biomarker of aging and a forecaster of longevity in humans. Leukocyte telomere length is heritable, longer in women than in men, and is relatively shorter in persons who suffer from aging-related diseases, cardiovascular diseases in particular. This study found in four different populations that leukocyte telomere length in adult offspring was positively correlated with paternal age at the time of birth of the offspring. Analysis of telomeres in sperm of young (<30 years) and older (>50 years) donors revealed the emergence in the older donors of a subset of sperm with elongated telomeres. The mechanisms behind this enigmatic, age-dependent elongation in telomere length of sperm are unknown but may relate to epigenetic factors or the survival of a subset of germ-line stem cells, resilient against aging. It is also unknown how older fathers endow their offspring with longer telomeres in their leukocytes. The potential impact of paternal age on leukocyte telomere length and, conceivably, aging-related diseases and longevity in the offspring is of relevance because offspring of older fathers comprise an increasing proportion of society.
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