Tessier Anne-Julie, Wang Fenglei, Liang Liming, Wittenbecher Clemens, Haslam Danielle E, Eliassen A Heather, Tobias Deirdre K, Li Jun, Zeleznik Oana A, Ascherio Alberto, Sun Qi, Stampfer Meir J, Grodstein Francine, Rexrode Kathryn M, Manson JoAnn E, Balasubramanian Raji, Clish Clary B, Martínez-González Miguel A, Chavarro Jorge E, Hu Frank B, Guasch-Ferré Marta
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Med. 2024 Mar 8;5(3):224-238.e5. doi: 10.1016/j.medj.2024.01.010. Epub 2024 Feb 15.
A healthy lifestyle is associated with a lower premature mortality risk and with longer life expectancy. However, the metabolic pathways of a healthy lifestyle and how they relate to mortality and longevity are unclear. We aimed to identify and replicate a healthy lifestyle metabolomic signature and examine how it is related to total and cause-specific mortality risk and longevity.
In four large cohorts with 13,056 individuals and 28-year follow-up, we assessed five healthy lifestyle factors, used liquid chromatography mass spectrometry to profile plasma metabolites, and ascertained deaths with death certificates. The unique healthy lifestyle metabolomic signature was identified using an elastic regression. Multivariable Cox regressions were used to assess associations of the signature with mortality and longevity.
The identified healthy lifestyle metabolomic signature was reflective of lipid metabolism pathways. Shorter and more saturated triacylglycerol and diacylglycerol metabolite sets were inversely associated with the healthy lifestyle score, whereas cholesteryl ester and phosphatidylcholine plasmalogen sets were positively associated. Participants with a higher healthy lifestyle metabolomic signature had a 17% lower risk of all-cause mortality, 19% for cardiovascular disease mortality, and 17% for cancer mortality and were 25% more likely to reach longevity. The healthy lifestyle metabolomic signature explained 38% of the association between the self-reported healthy lifestyle score and total mortality risk and 49% of the association with longevity.
This study identifies a metabolomic signature that measures adherence to a healthy lifestyle and shows prediction of total and cause-specific mortality and longevity.
This work was funded by the NIH, CIHR, AHA, Novo Nordisk Foundation, and SciLifeLab.
健康的生活方式与较低的过早死亡风险和较长的预期寿命相关。然而，健康生活方式的代谢途径及其与死亡率和寿命的关系尚不清楚。我们旨在识别并重复一种健康生活方式的代谢组学特征，并研究其与全因死亡率和特定病因死亡率风险以及寿命的关系。
在四个包含13056名个体且随访28年的大型队列中，我们评估了五个健康生活方式因素，使用液相色谱质谱法分析血浆代谢物，并通过死亡证明确定死亡情况。使用弹性回归识别独特的健康生活方式代谢组学特征。多变量Cox回归用于评估该特征与死亡率和寿命的关联。
所识别的健康生活方式代谢组学特征反映了脂质代谢途径。较短且饱和度更高的三酰甘油和二酰甘油代谢物组与健康生活方式得分呈负相关，而胆固醇酯和磷脂酰胆碱缩醛磷脂组呈正相关。具有较高健康生活方式代谢组学特征的参与者全因死亡率风险降低17%，心血管疾病死亡率降低19%，癌症死亡率降低17%，达到长寿的可能性增加25%。健康生活方式代谢组学特征解释了自我报告的健康生活方式得分与全因死亡率风险之间38%的关联以及与寿命之间49%的关联。
本研究识别出一种代谢组学特征，可衡量对健康生活方式的依从性，并显示出对全因死亡率、特定病因死亡率和寿命的预测作用。
本研究由美国国立卫生研究院、加拿大卫生研究院、美国心脏协会、诺和诺德基金会和瑞典国家生命科学实验室资助。
