Department of Public Health, Danish Aging Research Center, University of Southern Denmark, Odense, Denmark.
Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
Aging Cell. 2020 Oct;19(10):e13228. doi: 10.1111/acel.13228. Epub 2020 Sep 4.
The familial resemblance in length of adult life is very modest. Studies of parent-offspring and twins suggest that exceptional health and survival have a stronger genetic component than lifespan generally. To shed light on the underlying mechanisms, we collected information on Danish long-lived siblings (born 1886-1938) from 659 families, their 5379 offspring (born 1917-1982), and 10,398 grandchildren (born 1950-2010) and matched background population controls through the Danish 1916 Census, the Civil Registration System, the National Patient Register, and the Register of Causes of Death. Comparison with the background, population revealed consistently lower occurrence of almost all disease groups and causes of death in the offspring and the grandchildren. The expected incidence of hospitalization for mental and behavioral disorders was reduced by half in the offspring (hazard ratio 0.53, 95% confidence interval 0.45-0.62) and by one-third in the grandchildren (0.69, 0.61-0.78), while the numbers for tobacco-related cancer were 0.60 (0.51-0.70) and 0.71 (0.48-1.05), respectively. Within-family analyses showed a general, as opposed to specific, lowering of disease risk. Early parenthood and divorce were markedly less frequent in the longevity-enriched families, while economic and educational differences were small to moderate. The longevity-enriched families in this study have a general health advantage spanning three generations. The particularly low occurrence of mental and behavioral disorders and tobacco-related cancers together with indicators of family stability and only modest socioeconomic advantage implicate behavior as a key mechanism underlying familial aggregation of exceptional health and survival.
长寿家族的成年后寿命具有明显的相似性。对父母-子女和双胞胎的研究表明，异常的健康和生存比一般寿命具有更强的遗传成分。为了阐明潜在的机制，我们从 659 个家庭中收集了丹麦长寿兄弟姐妹（1886-1938 年出生）的信息，他们的 5379 个后代（1917-1982 年出生）和 10398 个孙辈（1950-2010 年出生），并通过丹麦 1916 年人口普查、民事登记系统、国家患者登记处和死因登记处与背景人口对照进行匹配。与背景人群相比，后代和孙辈的几乎所有疾病组和死因的发生频率都持续较低。后代的精神和行为障碍住院预期发生率降低了一半（危险比 0.53，95%置信区间 0.45-0.62），孙辈降低了三分之一（0.69，0.61-0.78），而与烟草相关的癌症的数量分别为 0.60（0.51-0.70）和 0.71（0.48-1.05）。家族内分析显示出一般而非特定的疾病风险降低。长寿富集家庭中的早育和离婚明显较少，而经济和教育差异较小到中等。本研究中的长寿富集家庭具有跨越三代的整体健康优势。精神和行为障碍以及与烟草相关的癌症的发生率特别低，加上家庭稳定性的指标和适度的社会经济优势，表明行为是异常健康和生存的家族聚集的关键机制。
