Identifying Multi-Scale Mechanisms for Age-Related Increase in Metabolic Cost of Walking - Mobility serves as a surrogate for well-being with age-related limits to walking function that include: increased energy cost and decreased speed. In 2021, the National Institute on Aging convened interdisciplinary scientists to identify multi-scale mechanisms for mobility impairments in aging and identified multiple factors contributing to elevated metabolic cost and reduced walking speed. A foundational age-related difference in walking function emerged - the so called ‘distal to proximal shift’ in neuromechanical effort. Older walkers rely more on proximal hip rather than distal ankle muscle-tendons to power gait. This proposal leverages a multi-scale, computational-experimental approach to probe cellular-to-behavioral mechanisms linking the ‘distal-to proximal’ shift to increased energy cost and decreased walking speed with age. The central hypothesis is that older adults select slower gait speeds to prioritize stability over economy, and these ‘safer’, proximally- biased gaits combine with declines in neuromuscular efficiency creating a ‘lose-lose’ combination that elevates the metabolic cost of walking. Aim 1: Characterize age-related differences in the relationship between lower-limb joint mechanics and metabolic cost of ‘ecologically-relevant’ walking. Approach: GaTech will recruit n=60 [n=30 (15M/15F) young adults (YA) 18 – 30y and n=30 (15M/15F) older adults (OA-sed) ≥60y]. Outcomes: Net metabolic power, lower-limb muscle activity and joint kinematics/kinetics during ‘ecologically-relevant’ outdoor walking with a novel sensor suit using custom-trained machine-learning algorithms. Ankle and hip exoskeletons to probe joint-level mechanical efficiency. Expected results: OA-sed>YA net metabolic power associated with higher, more proximal and less efficient lower-limb joint power. Aim 2: Examine how age-related changes in proximal-to-distal musculotendon structure and cellular/molecular muscle function impact metabolic cost of walking. Approach: IHMC will recruit YA+OA-sed (same as Aim 2) plus n=30 (15M/15F) ≥60y physically activity OA (OA-fit). Outcomes: Treadmill outcomes from Aim 2, distal-to-proximal musculotendon profiling, lateral gastrocnemius (distal) and vastus lateralis (proximal) muscle biopsies for mitochondrial function, myofiber type/size/grouping, targeted mitochondrial/metabolic molecular analyses. Expected results: OA-sed < OA-fit <YA net metabolic power associated with proximally-biased reductions in muscle force capacity/mitochondrial function. Aim 3: Determine the influence of task-level priorities on observed age-related increases in metabolic cost of walking. Approach: Predictive musculoskeletal simulations that satisfy a pre-defined walking energy- stability criterion. Outcomes: Predicted lower-limb muscle activations, joint and musculotendon kinematics and kinetics, and metabolic energy cost of walking for simulations with old vs. young. Expected results. Data-driven simulations will match experimental muscle activations from Aims1+2. Impact: Computational-experimental approach identifies key age-related differences in muscle biology, musculotendon structure-function, joint-level mechanics and task-level prioritization that drive elevated metabolic cost of walking in aging.
