The plasma metabolome as a predictor of biological aging in humans

Abstract

Chronological age is an important predictor of morbidity and mortality; however, it is unable to account for heterogeneity in the decline of physiological function and health with advancing age. Several attempts have been made to instead define a "biological age" using multiple physiological parameters in order to account for variation in the trajectory of human aging; however, these methods require technical expertise and are likely too time-intensive and costly to be implemented into clinical practice. Accordingly, we sought to develop a metabolomic signature of biological aging that could predict changes in physiological function with the convenience of a blood sample. A weighted model of biological age was generated based on multiple clinical and physiological measures in a cohort of healthy adults and was then applied to a group of healthy older adults who were tracked longitudinally over a 5-10-year timeframe. Plasma metabolomic signatures were identified that were associated with biological age, including some that could predict whether individuals would age at a faster or slower rate. Metabolites most associated with the rate of biological aging included amino acid, fatty acid, acylcarnitine, sphingolipid, and nucleotide metabolites. These results not only have clinical implications by providing a simple blood-based assay of biological aging, but also provide insight into the molecular mechanisms underlying human healthspan.

Urine Untargeted Metabolomic Profiling Is Associated with the Dietary Pattern of Successful Aging among Malaysian Elderly

“…For each bucket data, the corresponding p -valued was calculated. In order to address false discovery rate (FDR) from multiple comparison, Benjamini–Hocherberg correction (0.10) was applied on each pair of analysis [ 10 , 36 ].…”

“…The profile of metabolites using serum, plasma, saliva, and cerebrospinal fluid in relation to mild cognitive impairment, dementia, and Alzheimer’s disease has been widely performed [ 1 , 5 , 6 , 7 , 8 , 9 ]. There are metabolomic studies related to health span and biological aging in human [ 10 , 11 , 12 ]. Amino acid metabolites and lipid associated with health span indicator and rate of biological aging.…”

“…Amino acid metabolites and lipid associated with health span indicator and rate of biological aging. Higher concentration of plasma metabolites from TCA cycle, i.e., citrate and tryptophan metabolism were associated with lower biological age [ 10 , 12 ]. However, the metabolites that are likely to be biomarkers for successful aging (SA) remain unknown.…”

Urinary metabolic signatures reflect cardiovascular risk in the young, middle-aged, and elderly populations

“…Thus, novel tools to improve cardiovascular risk assessment are needed to better stratify young individuals and more precisely define whom to target for personalized intervention. At the other extreme, old age is a major risk factor for CVD; however, individuals of the same chronological age may differ considerably with respect to their overall health status, thus limiting the predictive capacity of chronological age alone in determining overall disease risk [ 10 ]. Indeed, conventional cardiovascular risk estimators underestimate survival in the elderly [ 11 ], and this can result in overmedication [ 12 ].…”

N-terminal pro B-type natriuretic peptide (NT-proBNP): a possible surrogate of biological age in the elderly people

“…Telomere length in leukocytes (Sanders and Newman 2013), perhaps the most popular and reliable indicator of biological age, although not routinely measurable 3. Proteomic and metabolomic indices (Menni et al 2015;Johnson et al 2019), which however are supported by still scarce and poorly conclusive studies 4. Magnetic resonance imaging to assess brain age, which is associated with cognitive decline and biological age (Cole et al 2018;Elliott et al 2019) 5.…”