科学家发现了一种方法，可以抵消60%以上的寿命缩短基因的影响

诸平

New research indicates that a healthy lifestyle can significantly lessen the impact of genes predisposed to shorten life, potentially by more than 60%. The study utilized data from over 350,000 individuals in the UK Biobank to analyze the effects of genetic risks and lifestyle factors on lifespan. It found that unfavorable lifestyles and genetic predispositions independently increase the risk of premature death, highlighting the importance of healthy behaviors in extending life expectancy, particularly for those at genetic risk. Credit: SciTechDaily.com

据《英国医学杂志》（BMJ）出版商2024年5月2日提供的消息，中英科学家合作发现了一种长寿方法，可以抵消60%以上的寿命缩短基因的影响（Live Longer: Scientists Discover Method To Offset Effects of Life-Shortening Genes by Over 60%）。

新的研究表明，健康的生活方式可以显著减少易导致寿命缩短的基因的影响，可能减少60%以上。这项研究利用了英国生物银行（UK Biobank）超过35万人的数据，分析了遗传风险和生活方式因素对寿命的影响。研究发现，不良的生活方式和遗传倾向各自增加了过早死亡的风险，强调了健康行为对延长预期寿命的重要性，特别是对那些有遗传风险的人。

不健康的生活方式会使死亡风险增加78%，无论遗传倾向如何。2024年4月29日发表在《英国医学杂志循证医学》(BMJ Evidence-Based Medicine)上的一项对多项广泛长期研究数据的分析表明，采用健康的生活方式可以抵消导致寿命缩短60%以上的基因的影响。原文详见：Zilong Bian, Lijuan Wang, Rong Fan, Jing Sun, Lili Yu, Meihong Xu, Paul R H J Timmers, Xia Shen, James F Wilson, Evropi Theodoratou, Xifeng Wu, Xue Li. Genetic predisposition, modifiable lifestyles, and their joint effects on human lifespan: evidence from multiple cohort studies. BMJ Evidence-Based Medicine, 29 April 2024: bmjebm-2023-112583. DOI: 10.1136/bmjebm-2023-112583. https://doi.org/10.1136/bmjebm-2023-112583

参与此项研究的有来自中国浙江大学医学院（Zhejiang University School of Medicine, Hangzhou, China）、南京医科大学公共卫生学院（School of Public Health, Nanjing Medical University, Nanjing, China）、北京大学公共卫生学院（School of Public Health, Peking University, Beijing, China）、复旦大学（Fudan University, Shanghai, China）、浙江省预防智能医学重点实验室（The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, China）以及英国爱丁堡大学（University of Edinburgh, Edinburgh, UK）的研究人员。

虽然基因和生活方式似乎对一个人的寿命有叠加效应，但研究表明，不健康的生活方式与早逝的风险增加了78%，与遗传倾向无关。多基因风险评分(polygenic risk score简称PRS)结合多种遗传变异来得出一个人的总体遗传倾向，从而延长或缩短寿命。生活方式是一个关键因素，其中包括吸烟、饮酒、饮食质量、睡眠配额和身体活动水平。

但研究人员说，目前还不清楚健康的生活方式能在多大程度上抵消基因对寿命缩短的影响。为了进一步探索这一点，他们在2006~2010年期间招募了353742名成年人，他们的健康状况一直被追踪到2021年。使用来自LifeGen队列研究的数据，得出了长期(20%的参与者)、中期(60%的参与者)和短期(20%的参与者)寿命风险的多基因风险评分。

加权健康生活方式评分，包括目前不吸烟、适度饮酒、有规律的体育活动、健康的体型、充足的睡眠和健康的饮食，使用美国全国健康和营养调查(National Health And Nutrition Examination Survey简称NHANES)研究的数据，将其分为有利(23%的参与者)、中等(56%的参与者)和不利(22%的参与者)的生活方式。

生活方式和遗传风险的结果（Results of Lifestyle and Genetic Risk）

在近13年的平均追踪期内，24239名参与者死亡。无论他们的生活方式如何，那些基因上倾向于短寿命的人比那些基因上倾向于长寿命的人早死的可能性高21%。同样，与遗传倾向无关，生活方式不良的人比生活方式良好的人过早死亡的可能性高出78%。

那些在遗传上有缩短寿命风险的人以及生活方式不佳的人死亡的可能性是那些遗传上有长寿倾向的人以及生活方式良好的人的两倍。有4个因素似乎构成了最佳的生活方式组合:不吸烟;有规律的身体活动;充足的夜间睡眠;还有健康的饮食。

这是一项观察性研究，因此，无法得出关于因果关系的明确结论，此外，研究人员承认他们的发现存在各种局限性。例如，生活方式只在一个时间点进行评估，而生活方式的选择因年龄而异。研究人员说，参与者也都是欧洲血统，这可能限制了研究结果的普遍性。然而，他们认为，他们的发现表明，寿命较短或过早死亡的遗传风险可能被良好的生活方式抵消62%左右。

他们建议，那些寿命缩短的遗传风险较高的人，在40岁时，如果有健康的生活方式，他们的预期寿命可以延长近5.5年。他们补充说，鉴于生活习惯往往在中年之前就已经形成，因此需要在此之前采取措施，减轻寿命缩短的遗传易感。

他们总结说，“这项研究阐明了健康的生活方式在减轻遗传因素对寿命减少的影响方面的关键作用。改善健康生活方式的公共卫生政策将成为传统卫生保健的有力补充，并减轻遗传因素对人类寿命的影响。”

此研究得到了浙江省杰出青年自然科学基金(Natural Science Fund for Distinguished Young Scholars of Zhejiang Province LR22H260001))、中国国家自然科学基金(National Nature Science Foundation of China 82204019)、浙江省预防智能医学重点实验室(Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province 2020E10004)、浙江省创新创业领军人才引进计划(Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang 2019R01007)、浙江省重点研发计划(Key Research and Development Program of Zhejiang Province 2020C03002)、健康浙江百万人队列(Healthy Zhejiang One Million People Cohort K-20230085)、中国国家留学基金委资助项目(China Scholarship Council 201909067018)；英国CRUK职业发展奖学金(CRUK Career Development Fellowship C31250/A22804)、MRC人类遗传学单位项目（MRC Human Genetics Unit program grant）以及健康和疾病的数量性状(Quantitative traits in health and disease (U. MC_UU_00007/10)的资助或支持。

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Abstract

Objective To investigate the associations across genetic and lifestyle factors with lifespan.

Design A longitudinal cohort study.

Setting UK Biobank.

Participants 353 742 adults of European ancestry, who were recruited from 2006 to 2010 and were followed up until 2021.

Exposures A polygenic risk score for lifespan with long (<lowest quintile), intermediate (quintiles 2 to 4), and short (>highest quintile) risk categories and a weighted healthy lifestyle score, including no current smoking, moderate alcohol consumption, regular physical activity, healthy body shape, adequate sleep duration, and a healthy diet, categorised into favourable, intermediate, and unfavourable lifestyles.

Main outcome measures Lifespan defined as the date of death or the censor date minus the date of birth.

Results Of the included 353 742 participants of European ancestry with a median follow-up of 12.86 years, 24 239 death cases were identified. Participants were grouped into three genetically determined lifespan categories including long (20.1%), intermediate (60.1%), and short (19.8%), and into three lifestyle score categories including favourable (23.1%), intermediate (55.6%), and unfavourable (21.3%). The hazard ratio (HR) of death for individuals with a genetic predisposition to a short lifespan was 1.21 (95% CI 1.16 to 1.26) compared to those with a genetic predisposition to a long lifespan. The HR of death for individuals in the unfavourable lifestyle category was 1.78 (95% CI 1.71 to 1.85), compared with those in the favourable lifestyle category. Participants with a genetic predisposition to a short lifespan and an unfavourable lifestyle had 2.04 times (95% CI 1.87 to 2.22) higher rates of death compared with those with a genetic predisposition to a long lifespan and a favourable lifestyle. No multiplicative interaction was detected between the polygenic risk score of lifespan and the weighted healthy lifestyle score (p=0.10). The optimal combination of healthy lifestyles, including never smoking, regular physical activity, adequate sleep duration, and a healthy diet, was derived to decrease risk of premature death (death before 75 years).

Conclusion Genetic and lifestyle factors were independently associated with lifespan. Adherence to healthy lifestyles could largely attenuate the genetic risk of a shorter lifespan or premature death. The optimal combination of healthy lifestyles could convey better benefits for a longer lifespan, regardless of genetic background.