RT Journal Article
SR Electronic
T1 The biphasic and age-dependent impact of Klotho on hallmarks of aging and skeletal muscle function
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.22.207043
DO 10.1101/2020.07.22.207043
A1 Abish Pius
A1 Zachary Clemens
A1 Sruthi Sivakumar
A1 Amrita Sahu
A1 Sunita Shinde
A1 Hikaru Mamiya
A1 Nathaniel Luketich
A1 Jian Cui
A1 Joerg D. Hoeck
A1 Sebastian Kreuz
A1 Michael Franti
A1 Aaron Barchowsky
A1 Fabrisia Ambrosio
YR 2020
UL http://biorxiv.org/content/early/2020/07/24/2020.07.22.207043.abstract
AB Aging is accompanied by a disrupted information flow, which results from accumulation of molecular mistakes. These mistakes ultimately give rise to debilitating disorders such as skeletal muscle wasting, or sarcopenia. To estimate the growing “disorderliness” of the aging muscle system, we employed a statistical physics approach to estimate the state parameter, entropy, as a function of genes associated with hallmarks of aging. Although the most prominent structural and functional alterations were observed in the oldest old mice (27-29 months), we found that the escalating network entropy reached an inflection point at old age (22-24 months). To probe the potential for restoration of molecular “order” and reversal of the sarcopenic phenotype, we overexpressed the longevity protein, α-Klotho. Klotho overexpression modulated genes representing all hallmarks of aging in both old and oldest-old mice. However, whereas Klotho improved strength in old mice, intervention failed to induce a benefit beyond the entropic tipping point.Competing Interest StatementJ.H., S.K., and M.F. are employees of Boehringer Ingelheim Pharmaceutical Company. The remaining authors declare no competing interests.