Abstract
Reduced walking speed is a hallmark of functional decline in aging across species. An age-related change in walking style may represent an additional key marker signifying deterioration of the nervous system. Due to the speed dependence of gait metrics combined with slowing of gait during aging, it has been challenging to determine whether changes in gait metrics represent a change in style. In this longitudinal study we employed gait signatures to separate changes in walking style and speed in mice. We compared gait signatures at mature adult age with middle aged, old and geriatric time points and included female and male sub-cohorts to examine sex differences in nature or timing signature shifts. To determine whether gait signature shifts occurred independently from a decline in other mobility domains we measured balance and locomotor activity. We found that walking speed declined early, whereas gait signatures shifted very late during the aging process. Shifts represented longer swing time and stride length than expected for speed, as in slow motion, and were preceded by a decline in other mobility domains. The pattern of shifts was similar between female and male cohorts, but with sex differences in timing. We conclude that changes in walking style, speed and other mobility domains represent separate age-related phenomena. These findings call for careful, sex specific selection of type and timing of outcome measures in mechanistic or interventional studies. The pattern of age-related gait signature shifts is distinct from patterns seen in neurodegenerative conditions and may be a translatable marker for the end of the lifespan.
Highlights
While gait signatures can be reconstructed for both fore- and hindlimbs (Broom et al, 2019), here we focus on hindlimb metrics as these are most important for propulsion and are most relevant for human gait comparisons
We found that despite an early decline in walking speed and other mobility domains, gait signatures were stable well into old age (Figure 7)
Gait signatures shifted at the geriatric time point, with swing time and stride length being longer than expected for speed
Summary
Decreased gait speed is a major hallmark for dysfunction and physical frailty in old age (Fried et al, 2001; Ko et al, 2010; Buchman et al, 2014; Middleton et al, 2015; Herssens et al, 2018; Grande et al, 2019) and is a predictor for adverse outcomes such as disability, cognitive impairment, institutionalization, falls, and/or mortality (Abellan van Kan et al, 2009; Mielke et al, 2013; White et al, 2013; Veronese et al, 2018; Semba et al, 2020). While there are many valid methods to capture gait metrics in human or animal models, the challenge lies in the interpretation of changes in gait metrics in the setting of declining speed: key gait metrics that dictate speed, i.e., stride length, stance time and swing time and their derivatives, change as a function of speed and do so independently (Figure 1; Broom et al, 2017; Mock et al, 2018). This problem is further magnified when datasets are averaged. Little is known about changes in walking style and underlying circuit mechanisms (Wilson et al, 2019)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call