The primary goal is to develop a multidomain intervention program focused on preserving global or regional brain volume and functions while simultaneously improving physical mobility and cognitive functions in older individuals with mobility frailty. This initiative seeks to unravel the brain-muscle axis mechanisms contributing to the accelerated functional declines observed in older populations. Moreover, our objective includes examining the relationships between the intervention and a broad spectrum of clinical characteristics, phenotypic traits, biochemical profiles, myokines, proteomics, metabolomics, brain imaging, and our previously identified discoveries involving exosomal miRNA.

This study is a randomized controlled trial of 12-month multidomain intervention program among community-living older adults with early physical or cognitive impairments. Inclusion criteria are: (1) community-dwelling adults aged ≥ 65 years, (2) slow gait speed (\<1 m/s in 6-meter walk test) or weakness (dominant handgrip strength \<28 kg in men, \<18 kg in women); subjects with the following conditions will be excluded: (1) established diagnosis of dementia, Parkinsonism or other neurodegenerative disease (2) disable status: mobility-limiting conditions, (3) active, acute diseases receiving treatment, such as cancer, heart failure, COPD and so on, (4) estimated life expectancy \<12 months, (5) current nursing home residents.