Metabolic Markers Demonstrate the Heterogeneity of Walking Ability in Non-Disabled Community-Dwelling Older Adults

<b>Background</b>: Walking ability is important for the quality of life of older adults. A self-reported walking ability index (WAI) covering the difficulty and ease of walking captures a broader spectrum of walking ability in healthy older persons. <b>Methods</b>: Using metabolomics in the Health, Aging and Body Composition study, we identified Year 2 metabolites cross-sectionally and longitudinally related to WAI (0-9, higher scores indicate better walking ability) using probabilistic index models and multinomial logistic models, respectively. <b>Results</b>: Among 2334 participants (mean age 74.6 years, 51% women, 37% Black), 27% scored 0-5, 36% scored 6-8, and 37% scored 9 at Year 2. Over 4 years, 52% maintained a stable WAI, 6% improved, while 42% declined (22% 1-2 points and 20% >2 points decline). We identified 81 metabolites significantly associated with both poorer concurrent WAI and faster decline, including higher acylcarnitine species, shorter-chain saturated diglycerides and triglycerides, and TCA cycle intermediates (cis-aconitic, fumaric, and malic acids), and lower phospholipids levels. Eighteen additional metabolites were only associated with faster WAI decline: higher short-chain saturated triglycerides and energy metabolism markers (ATP/ADP/AMP) and lower margaric acid and glycine levels. Notably, those with improved WAI, despite poorer baseline WAI and lifestyles, showed more favorable metabolic profiles than others. <b>Conclusions</b>: Metabolites linked to the TCA cycle and energy metabolism, as well as inflammation and protein catabolism, were related to mobility function. Some metabolites might be particularly important for the early detection of older adults at risk of mobility decline. Metabolic profiles may also help identify older individuals (i.e., with improving WAI) with greater metabolic resilience to lifestyle risk factors and health conditions.