1H NMR-Based Metabolomics Reveals the Intrinsic Interaction of Age, Plasma Signature Metabolites, and Nutrient Intake in the Longevity Population in Guangxi, China

Abstract

Health and longevity populations have distinct metabolic and nutrient intake profiles. However, the relationship between biomarkers of longevity-related metabolites and dietary nutrient intake profiles, as well as metabolic markers associated with longevity features, have not been fully elucidated. Therefore, 1H nuclear magnetic resonance (1H NMR)-based plasma metabolomics profiling was conducted in the present study to identify potential metabolites which can be used as specific markers for the evaluation of healthy aging. Plasma samples were obtained from centenarians and nonagenarians from the longevous region, and elderly participants aged 60–89 from the longevous region, as well as a low centenarian ratio region. The results showed that participants from longevous regions exhibited higher plasma levels of citrate, tyrosine, choline, carnitine, and valine, as well as lower contents of VLDL, lactate, alanine, N-acetyl glycoprotein (NAG), trimethylamine oxide (TMAO), α-glucose, β-glucose, and unsaturated lipids. The differential plasma metabolites were associated with an alteration in glycolysis/gluconeogenesis; aminoacyl-tRNA biosynthesis; alanine, aspartate, and glutamate metabolism; and phenylalanine, tyrosine, and tryptophan biosynthesis in participants from longevous regions. The signature metabolites were associated with higher dietary fiber intake, as well as lower energy and fat intake. The results of the present study demonstrate key longevity signature metabolites in plasma, and the dietary patterns identified provide a basis for further health and longevity research.

The metabolomics of human aging: Advances, challenges, and opportunities

“…In population studies, this complexity seems to appear with inconsistent directions of effect in the association of BCAAs with age. Valine was positively associated with age in women ( 24 , 54 ) and in centenarians/nonagenarians compared to typical elderly ( 58 ) but negatively associated with age in men ( 50 ). Isoleucine was also associated with age in inconsistent directions: studies have reported an increase in CSF ( 53 ), decrease in plasma ( 40 , 50 ), and increase in plasma ( 24 , 34 ).…”

“…These lipids tended to increase starting around the 30s for men but not until around age 50 for women, a finding the authors suggested might be driven by the timing of menopause for women. While VLDL typically increases with age, Li et al ( 58 ) found that VLDL was lower among long-lived groups, including centenarians and nonagenarians, compared to a reference elderly population aged 60 to 89. MS-based studies have identified similar changes as these studies, including higher cholesterol associated with age in women ( 40 ), higher PUFAs with age ( 45 ), and a general implication of altered lipids and lipid metabolism with aging ( 38 ).…”

“…Many studies have also implicated the renal system and excretion. Researchers have noted altered levels of several metabolites as potentially indicative of changes in kidney function (declining with age) or urea metabolism, including aging-related increases in urea (blood) ( 26 ), ornithine (blood) ( 26 ), trimethylamine N -oxide (TMAO; urine and plasma) ( 27 , 58 ), glutamine (urine) ( 35 ), citrulline [red blood cells (RBCs)] ( 39 ), pantothenate (RBCs) ( 39 ), dimethyl guanosine (RBCs) ( 39 ), and N -acetyl-arginine (RBCs) ( 39 ) and decreases in β-hydroxy-β-methylbutyrate (HMB; urine) ( 32 ) and 1,5-anhydroglucitol (RBCs) ( 39 ). Studies have also found an enrichment of urea cycle metabolites in metabolomic clock models ( 46 ) and metabolites associated with menopause ( 54 ).…”

The Age-Accompanied and Diet-Associated Remodeling of the Phospholipid, Amino Acid, and SCFA Metabolism of Healthy Centenarians from a Chinese Longevous Region: A Window into Exceptional Longevity

“…Second, the two kinds of different biological samples, including urine and feces, were analyzed to comprehensively assess the metabolic features of healthy centenarians from different perspectives. To date, most of the relevant reports primarily focus on metabolites in serum and plasma [ 3 , 4 , 5 , 6 , 14 , 15 , 16 , 40 ]. Collino et al explored the metabolic changes in serum and urine of Italian centenarians [ 1 ].…”

Protection effect of gut microbiota composition and acetate absorption against hypertension-induced damages on the longevity population in Guangxi, China

“…Participants’ dietary and nutritional status was assessed using a semi-quantitative food frequency questionnaire (FFQ), which was recorded for consecutive 7-days at home ( 23 , 24 ). All participants were asked to adopt the mode of individual dining and were urged to maintain their usual eating patterns at home during the dietary survey.…”