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

• DOI: 10.7554/elife.61138
• Publication Date: 2021-04-20T00:01:50Z
• Authors: Zachary Clemens; Sruthi Sivakumar; Abish Pius; Amrita Sahu; Sunita Shinde; Hikaru Mamiya; Nathaniel Luketich; Jian Cui; Purushottam Dixit; Joerg D Hoeck; Sebastian Kreuz; Michael Franti; Aaron Barchowsky; Fabrisia Ambrosio
• Keywords: Klotho; Senescence

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 growing ‘disorderliness’ aging muscle, we employed statistical physics approach estimate the state parameter, entropy, as function genes associated with hallmarks aging. Escalating network entropy reached an inflection point at old age, while structural and functional alterations progressed into oldest-old age. probe potential for restoration ‘order’ reversal sarcopenic phenotype, systemically overexpressed longevity protein, Klotho, via AAV. Klotho overexpression modulated representing all in mice, but pathway enrichment revealed directions changes were, many genes, age-dependent. Functional improvements were also improved strength failed induce benefits beyond entropic tipping point.