The biphasic and age-dependent impact of klotho on hallmarks of aging and skeletal muscle function.
Elife
; 102021 04 20.
Article
em En
| MEDLINE
| ID: mdl-33876724
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 hallmarks of aging in old and oldest-old mice, but pathway enrichment revealed directions of changes were, for many genes, age-dependent. Functional improvements were also age-dependent. Klotho improved strength in old mice, but failed to induce benefits beyond the entropic tipping point.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Envelhecimento
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Músculo Esquelético
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Sarcopenia
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Glucuronidase
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Elife
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos