In a recent study published in the journal med, The researchers used a matched dataset comprised of four American sample cohorts to identify metabolomic markers of a healthy lifestyle and potentially the mechanisms underlying their generation. They used a combination of analytical techniques, specifically liquid chromatography and mass spectrometry, on 13,056 datasets and found that the metabolomic signature of a healthy lifestyle primarily reflects lipid metabolic pathways. I observed.
A shorter, more saturated set of di- and triacylglycerol metabolites were found to be inversely correlated with a healthy lifestyle, while phosphatidylcholine plasmalogens and cholesteryl esters were found to be directly associated with symptoms. Encouragingly, the relative concentrations of these biomarkers reduced the risk of all-cause mortality by 17%, cardiovascular disease-related mortality by 19%, cancer-related mortality by 17%, and odds of 25%. % improved. achieving longevity.
Study: Relationship between healthy lifestyle plasma metabolites and mortality and longevity: four prospective US cohort studies
The relationship between lifestyle choices and metabolic health
The prevalence of chronic non-communicable diseases is now higher than ever before, and the main causes are diet (e.g. Western diet) and physical activity levels (e.g. sedentary lifestyle). Previous research has highlighted the great benefits of adopting a healthy lifestyle, with a study of an American cohort showing that individuals who maintained a body mass index (BMI) between 18.5 and 24.9 kg/m found that the risk of all-cause mortality was reduced by 55-71%.2consumed alcohol in moderation, participated in physical activity, and refrained from smoking.
Unfortunately, the mechanisms underlying these interactions remain largely unknown. Several studies have shown that elements of individual health behavior, such as weight, diet, alcohol intake, physical activity, and smoking, may be associated with metabolomic signatures indicative of current and past health status. It is suggested. Yet, these hypotheses are rarely tested within a scientific framework. Although sometimes confusing, limited information in this field suggests that polyunsaturated fatty acids (PUFAs), phosphatidylcholine (PC), glutamic acid and similar amino acids (AAs) are associated with improved health outcomes. whereas triacylglycerol (TAG), sphingomyelin (SM), and carnitine are associated with suboptimal carnitine.
“However, most studies have only investigated dietary and physical activity factors, with small sample sizes and profiled a limited set of metabolites. A comprehensive understanding of a given metabolic pathway has yet to be discovered; studying several modifiable lifestyle factors simultaneously can improve our understanding of common biological mechanisms and important differences. I guess.”
About research
In this study, researchers used lifestyle, metabolomics, and clinical information from four American cohorts of more than 13,000 people to create a metabolomics-based midlife healthy lifestyle score. , and further investigated the relationship between this score and mortality and longevity outcomes. . Outcome follow-up was extensive, with a mean duration of 28 years. Cohorts include the Nurses' Health Study (NHS; 1976), her second iteration of the same prospective cohort (NHSII; 1989), the Women's Health Initiative (WHI; 1993), and the Health Professionals Follow-up Study (HPFS; 1986). ) was included. ). They consisted of middle-aged (mean 54.3 years) women (85.8%) who were primarily Caucasian (96.7%).
Lifestyle information was reported by participants, clinical information was obtained from a prospective cohort database, and metabolomic information was obtained from (fasting) plasma samples obtained at study entry and subsequent follow-up. Individuals with missing data on measured outcomes (BMI, alcohol intake, metabolomic profiling, diet, physical activity level, smoking status) were excluded. The WHI cohort was used as an external validation cohort for the results obtained from the remaining three of his cohorts.
Plasma metabolome profiling uses acetonitrile/methanol/formic acid extraction followed by hydrophilic interaction liquid chromatography (HILIC) and positive ionization mass spectrometry (MS) for polar compounds (such as amino acids) and isopropanol extraction followed by octyl Performed using high performance fluids. Lipid chromatography (HPLC) and positive ionization MS. The Metabolite Standard Initiative (MSI) database was used to identify the resulting metabolites.
Lifestyle factors (treatment) were categorized into five main categories: diet, alcohol intake, physical activity, smoking, and BMI and were assessed using questionnaires and the Alternative Healthy Eating Index (AHEI). Mortality and life expectancy (outcomes) were obtained from family reports (for deaths), state statistical records, and the National Mortality Index database. Multivariable linear regression, logistic regression, and elastic linear regression were used for statistical data analysis. Cox proportional hazard ratios were calculated to convert these results into relative disease risks.
research result
The results revealed that the metabolomics signature that best reflected a healthy lifestyle was the lipid metabolic pathway consisting of the PC, TAG, CE, and DAG metabolite families. Diet composition and BMI were found to be the best predictors of positive metabolite signs. Metabolite characterization identified more than 400 metabolites associated with lifestyle choices. Elastic regression analysis identified 187 of these metabolites as explaining healthy lifestyle behaviors, with 58 positively correlated and 129 inversely associated with beneficial mortality and longevity outcomes. showed the relationship between
“…MSEA revealed that CE and PC, mainly composed of PUFA, are the most abundant set of metabolites that are positively associated with a healthy lifestyle. PC acts as a means of lipid storage and transport and has been shown to be reflex-prone “Its important role in cell membranes and membrane signaling is well known.”
Amino acids and metabolites involved in purine metabolism were also highlighted as characteristics of a healthy lifestyle. A vegetarian diet rich in circulating glycine, trigonelline, asparagine, hippuric acid, and glutamine and low in valine, isoleucine, and leucine was found to be more beneficial than dietary intake of red meat, poultry, and energy drinks.
Outcome analysis revealed a surprising fact. The metabolomic signatures identified here were better predictors of mortality and longevity than patient-reported fitness or health levels.
“In fact, metabolomic features explain 38.0% of the association between self-reported healthy lifestyle scores and mortality, indicating unique biological pathways captured by metabolomics. Consistent with the mortality results of explained 48.6% of the association. ”
conclusion
This study combined a large American cohort of more than 13,000 participants to identify metabolomic signatures associated with mortality and longevity outcomes as a result of healthy lifestyle and dietary choices. . Study results revealed that more than 100 metabolites are associated with (positive or negative) healthy lifestyle outcomes, most of which are involved in lipid metabolic pathways.
“…our findings suggest that increased adherence to a healthy lifestyle may lead to changes in the metabolome that are associated with lower risk of early death and increased likelihood of longevity. We identified metabolomic signatures associated with a combination of healthy lifestyles in U.S. adults that reflect lipid metabolic pathways: those with higher polymetabolite scores had lower overall mortality risk. “We found that they had a lower risk of death by cause and were more likely to live longer.”
Reference magazines:
- Tessier, A.-J., Wang, F., Liang, L., Wittenbecher, C., Haslam, DE, Eliassen, AH, Tobias, DK, Li, J., Zeleznik, OA, Ascherio, A., Sun. , Q., Stampfer, M.J., Grodstein, F., Rexrode, K.M., Manson, J.E., Balasubramanian, R., Kulish, C.B., Martínez-González, M.A., Chavarro, J.E., … Guash-Ferret, M. (2024). Healthy lifestyle plasma metabolites associated with mortality and longevity: Four US prospective cohort studies. in the med. Elsevier BV, DOI – 10.1016/j.medj.2024.01.010, https://www.cell.com/med/fulltext/S2666-6340(24)00040-0