The biphasic and age-dependent impact of klotho on hallmarks of aging and skeletal muscle function.

ABSTRACT: Aging is accompanied by disrupted information flow, resulting from accumulation of molecular mistakes. These mistakes ultimately give rise to debilitating disorders including skeletal muscle wasting, or sarcopenia. To derive a global metric of growing 'disorderliness' of aging muscle, we employed a statistical physics approach to estimate the state parameter, entropy, as a function of genes associated with hallmarks of aging. Escalating network entropy reached an inflection point at old age, while structural and functional alterations progressed into oldest-old age. To probe the potential for restoration of molecular 'order' and reversal of the sarcopenic phenotype, we systemically overexpressed the longevity protein, Klotho, via AAV. Klotho overexpression modulated genes representing all

SUBMITTER: Clemens Z 

PROVIDER: S-EPMC8118657 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature