Assessment of Plasma Phospholipid Very-Long-Chain Saturated Fatty Acid Levels and Healthy Aging.

Importance: Identifying novel factors that protect against age-related diseases and promote healthy aging is critical to public health. Higher levels of circulating very-long-chain saturated fatty acids (VLSFAs) are integrated biomarkers of diet and metabolism shown to have beneficial associations in cardiovascular disease and total mortality, but whether they are associated with overall healthy aging is unknown. Objective: To examine the association of circulating levels of 3 VLSFAs with unhealthy aging events, including incident chronic disease (cardiovascular disease, cancer, lung disease or severe kidney disease), physical dysfunction, and cognitive decline. Design, Setting, and Participants: This cohort study used 1992 to 2014 data from the Cardiovascular Health Study (CHS). The CHS is a multicenter, population-based study of cardiovascular disease among older adults. Among the 4559 CHS participants with available fatty acid data, 1879 participants who had an age-related event before their first measurement were excluded. Data analysis was performed in 2020. Main Outcomes and Measures: Plasma phospholipid VLSFA levels were measured by thin-layer chromatography followed by gas chromatography. The main outcome was the hazard ratio (HR) of an incident unhealthy aging event associated with serial measures of plasma arachidic acid, behenic acid, and lignoceric acid. Results: Among the 2680 study participants (976 men [36.4%]), the mean (SD) age was 74.7 (4.8) years old at entry. During a median (interquartile range) of 6.4 (2.9-12.9) years of follow-up, 2484 participants experienced an unhealthy event. Compared with the lowest quintile, levels of behenic acid in the highest quintile of the fatty acid distribution were associated with 15% lower risk of an unhealthy event (HR, 0.85; 95% CI, 0.74-0.97; P for trend = .01) after adjustment for demographic characteristics, lifestyle factors, and clinical conditions. In analogous comparisons, levels of lignoceric acid were similarly associated with 16% lower risk of an unhealthy event (HR, 0.84; 95% CI, 0.73-0.95; P for trend = .001). Conclusions and Relevance: These findings suggest that higher levels of circulating behenic acid and lignoceric acid are associated with lower risk of unhealthy aging events. These results highlight the need to explore determinants of circulating VLSFAs for potential novel efforts to promote healthy aging.

Mapping intersectional inequalities in biomarkers of healthy ageing and chronic disease in older English adults.

Chronic diseases and their inequalities amongst older adults are a significant public health challenge. Prevention and treatment of chronic diseases will benefit from insight into which population groups show greatest risk. Biomarkers are indicators of the biological mechanisms underlying health and disease. We analysed disparities in a common set of biomarkers at the population level using English national data (n = 16,437). Blood-based biomarkers were HbA1c, total cholesterol and C-reactive protein. Non-blood biomarkers were systolic blood pressure, resting heart rate and body mass index. We employed an intersectionality perspective which is concerned with how socioeconomic, gender and ethnic disparities combine to lead to varied health outcomes. We find granular intersectional disparities, which vary by biomarker, with total cholesterol and HbA1c showing the greatest intersectional variation. These disparities were additive rather than multiplicative. Each intersectional subgroup has its own profile of biomarkers. Whilst the majority of variation in biomarkers is at the individual rather than intersectional level (i.e. intersections exhibit high heterogeneity), the average differences are potentially associated with important clinical outcomes. An intersectional perspective helps to shed light on how socio-demographic factors combine to result in differential risk for disease or potential for healthy ageing.

Clinical Assessment of the NADome as Biomarkers for Healthy Aging.

Nicotinamide adenine dinucleotide (NAD+) and its related metabolites (NADome) are important endogenous analytes that are thought to play important roles in cellular metabolism, inflammation, oxidative stress, cancer, neurodegeneration, and aging in mammals. However, these analytes are unstable during the collection of biological fluids, which is a major limiting factor for their quantitation. Herein, we describe a highly robust and quantitative method using liquid chromatography coupled to tandem mass spectrometry to quantify the NADome in whole blood, plasma, mononuclear cells, platelets, cerebrospinal fluid (CSF), and urine. This methodology represents a "gold standard" of measure for understanding biological pathways and developing targeted pharmacological interventions to modulate NAD+ biosynthesis and NAD-dependent mediators in health and disease.