The Effect of Physiological Stimuli on Sarcopenia; Impact of Notch and Wnt Signaling on Impaired Aged Skeletal Muscle Repair

Arthur, Susan T.; Cooley, Ian D.

doi:10.7150/ijbs.4262

Cited by 99 publications

(93 citation statements)

References 294 publications

(755 reference statements)

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“…There is also evidence that dysfunctional Wnt signaling is pathogenic in many aging-related diseases. The decline of Wnt signaling with age contributes to the pathogenesis of osteoporosis (Almeida et al 2007;Bennett et al 2005), Alzheimer's disease, and Parkinson's disease (Berwick and Harvey 2012); increased Wnt signaling with age is thought to cause fibrosis in skeletal muscle, resulting in sarcopenia (Arthur and Cooley 2012); and a variant of TCF7L2, a transcriptional effector of the Wnt pathway, increases the risk of type II diabetes (Grant et al 2006). Attaining a greater understanding of the relationship between aging and Wnt signaling in vivo would be valuable in the study of age-associated diseases and changes in physiology.…”

Section: Introductionmentioning

confidence: 99%

The effects of aging on the expression of Wnt pathway genes in mouse tissues

Hofmann

McBryan

Adams

et al. 2014

AGE

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The Wnt signaling pathway is involved in the regulation of tissue patterning and organ development during embryogenesis and continues to contribute to the maintenance of tissue homeostasis in adulthood. Recently, Wnt signaling has also been implicated in the establishment and progression of replicative cellular senescence. Given the known roles of tissue homeostasis and cellular senescence in aging, we sought to determine whether Wnt signaling changes with age. We examined the expression of 84 Wnt pathway-related genes in the liver, lung, skeletal muscle, and brain tissue from young and old mice. Expression changes were compared with those seen in cellular senescence, and transcription factors that might mediate these changes were predicted bioinformatically. In aggregate, our data are indicative of a general decrease in Wnt signaling with age, especially in the lung and brain. Furthermore, the set of genes that are differentially expressed with age is distinct from the genes differentially expressed in cellular senescence. The transcription factors predicted to regulate these changes, Nf-κB, Myb, Nkx2-1, Nr5a2, and Ep300, are known to regulate inflammation, differentiation, lipid metabolism, and chromatin remodeling, all of which have previously been implicated in aging. Although our study does not address whether altered Wnt signaling is a cause or an effect of aging, the presence of a relationship between the two provides a starting point for further investigation.

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Section: Introductionmentioning

confidence: 99%

The effects of aging on the expression of Wnt pathway genes in mouse tissues

Hofmann

McBryan

Adams

et al. 2014

AGE

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“…Notch receptor activation usually controls myoblast proliferation, but in aged muscle there is a decreased Notch expression. The increased Wnt signaling with aging might promote the conversion of the satellite cells from a myogenic to a fibroblastic lineage, thus inhibiting myogenicity and contributing to muscle fibrosis and impaired muscle repair [96–98]. …”

Section: Musculoskeletal Age-related Modificationsmentioning

confidence: 99%

Interaction Between Bone and Muscle in Older Persons with Mobility Limitations

Ferrucci¹,

Baroni²,

Ranchelli³

et al. 2014

CPD

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Aging is associated with a progressive loss of bone-muscle mass and strength. When the decline in mass and strength reaches critical thresholds associated with adverse health outcomes, they are operationally considered geriatric conditions and named, respectively, osteoporosis and sarcopenia. Osteoporosis and sarcopenia share many of the same risk factors and both directly or indirectly cause higher risk of mobility limitations, falls, fractures and disability in activities of daily living. This is not surprising since bones adapt their morphology and strength to the long-term loads exerted by muscle during anti-gravitational and physical activities. Non-mechanical systemic and local factors also modulate the mechanostat effect of muscle on bone by affecting the bidirectional osteocyte-muscle crosstalk, but the specific pathways that regulate these homeostatic mechanisms are not fully understood. More research is required to reach a consensus on cut points in bone and muscle parameters that identify individuals at high risk for adverse health outcomes, including falls, fractures and disability. A better understanding of the muscle-bone physiological interaction may help to develop preventive strategies that reduce the burden of musculoskeletal diseases, the consequent disability in older persons and to limit the financial burden associated with such conditions. In this review, we summarize age-related bone-muscle changes focusing on the biomechanical and homeostatic mechanisms that explain bone-muscle interaction and we speculate about possible pathological events that occur when these mechanisms become impaired. We also report some recent definitions of osteoporosis and sarcopenia that have emerged in the literature and their implications in clinical practice. Finally, we outline the current evidence for the efficacy of available anti-osteoporotic and proposed anti-sarcopenic interventions in older persons.

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“…Por ejemplo, se ha reportado que el ejercicio aumenta el número de células satélite en animales jóvenes y viejos al igual que en adultos mayores. El ejercicio también parece favorecer la activación del receptor Notch de las células satélite así como su señalización intracelular (Arthur & Cooley, 2012). Por esto, un análisis proteómico combinado con un modelo sistemático de ejercicio podría contribuir a descubrir los factores que según circulan en el plasma de ratones jóvenes y viejos, que favorecen e inhiben la regeneración muscular respectivamente (las piezas faltantes en su rompecabezas).…”

Section: Parabiosis Heterocrónica Y Regeneración Del Músculo Esqueléticounclassified

Hoy Como Ayer. Parabiosis Y Su Combinación Con Otras Técnicas Para Descubrir Los Secretos De La Sangre

Dávila

2014

PensarMov.

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_________________________________________________________________________ ResumenLópez-Dávila, A. J. (2014). Hoy como ayer. Parabiosis y su combinación con otras técnicas para descubrir los secretos de la sangre. PENSAR EN MOVIMIENTO: Revista de Ciencias del Ejercicio y la Salud, 12 (1), 1-15. Este artículo repasa algunos descubrimientos importantes relacionados con la fisiología del ejercicio, los cuales han sido posibles gracias al modelo llamado parabiosis. La parabiosis es una preparación fisiológica experimental en la cual dos animales comparten una sola circulación sanguínea. Este método permite demostrar la existencia de factores circulantes en la sangre y el efecto que estos tienen sobre diferentes tejidos. Aunque esta técnica se ha practicado por más de 150 años, sigue siendo muy utilizada y sus alcances se han reforzado gracias al uso de los métodos modernos de la biología molecular como herramienta complementaria. Por medio de experimentos de parabiosis se ha demostrado que en la sangre de modelos animales circulan moléculas capaces -entre otras acciones-de: a) regular la masa grasa corporal por medio de retrocontrol negativo, b) reducir la hipertrofia cardiaca asociada a la disfunción diastólica que ocurre con el envejecimiento c) inhibir la neurogénesis en el giro dentado del hipocampo y causar disfunciones cognitivas, d) favorecer la remielinización de la médula espinal y e) activar o inhibir la regeneración del músculo esquelético que se da luego de una lesión. El constante descubrimiento de factores que circulan en la sangre y sus efectos en diversos órganos abren nuevas preguntas acerca de los mecanismos moleculares y celulares que explican estos fenómenos y su posible aplicación en la salud del ser humano. La fisiología del ejercicio es una herramienta valiosa para hallar las respuestas.

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The Effect of Physiological Stimuli on Sarcopenia; Impact of Notch and Wnt Signaling on Impaired Aged Skeletal Muscle Repair

Cited by 99 publications

References 294 publications

The effects of aging on the expression of Wnt pathway genes in mouse tissues

The effects of aging on the expression of Wnt pathway genes in mouse tissues

Interaction Between Bone and Muscle in Older Persons with Mobility Limitations

Hoy Como Ayer. Parabiosis Y Su Combinación Con Otras Técnicas Para Descubrir Los Secretos De La Sangre

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