López-de-Munain, A. (Adolfo)

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    Loss of the matrix metalloproteinase-10 causes premature features of aging in satellite cells
    (2023) Rodríguez-García, J.A. (José Antonio); Paramo, J.A. (José Antonio); Ullate-Agote, A. (Asier); Bobadilla, M. (Míriam); Machado, F. J. D. (Florencio J.D.); Paradas, C. (Carmen); Vallejo-Illarramendi, A. (Ainara); Orbe, J. (Josune); Ramos, L.I. (Luis Isaac); Baraibar-Churio, A. (Arantxa); Romero-Riojas, J.P. (Juan Pablo); Extramiana, L. (Leire); Cantero, G. (Gloria); Vilas-Zornoza, A. (Amaia); López-de-Munain, A. (Adolfo); Prosper-Cardoso, F. (Felipe); Pérez-Ruiz, A.I. (Ana Isabel); Sainz, N. (Neira); Abizanda-Sarasa, G. (Gloria); Aranguren, X.L. (Xabier L.)
    Aged muscles accumulate satellite cells with a striking decline response to damage. Although intrinsic defects in satellite cells themselves are the major contributors to aging-associated stem cell dysfunction, increasing evidence suggests that changes in the muscle-stem cell local microenvironment also contribute to aging. Here, we demonstrate that loss of the matrix metalloproteinase-10 (MMP-10) in young mice alters the composition of the muscle extracellular matrix (ECM), and specifically disrupts the extracellular matrix of the satellite cell niche. This situation causes premature features of aging in the satellite cells, contributing to their functional decline and a predisposition to enter senescence under proliferative pressure. Similarly, reduction of MMP-10 levels in young satellite cells from wild type animals induces a senescence response, while addition of the protease delays this program. Significantly, the effect of MMP-10 on satellite cell aging can be extended to another context of muscle wasting, muscular dystrophy. Systemic treatment of mdx dystrophic mice with MMP-10 prevents the muscle deterioration phenotype and reduces cellular damage in the satellite cells, which are normally under replicative pressure. Most importantly, MMP-10 conserves its protective effect in the satellite cell-derived myoblasts isolated from a Duchenne muscular dystrophy patient by decreasing the accumulation of damaged DNA. Hence, MMP-10 provides a previously unrecognized therapeutic opportunity to delay satellite cell aging and overcome satellite cell dysfunction in dystrophic muscles.
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    Association of lifestyle, inflammatory factors, and dietary patterns with the risk of suffering a stroke: A case–control study
    (Taylor & Francis, 2016) De-Arce-Borda, A.M. (Ana María); Blazquez, V. (Vanessa); Zulet, M.A. (María Ángeles); Goyenechea, E. (Estíbaliz); López-de-Munain, A. (Adolfo); Martinez, A. (Alfredo); Abete, I. (Itziar)
    Background: Lifestyle, including dietary patterns, could involve specific factors participating in inflammation that confer a higher risk of suffering a stroke. However, little attention has been apparently given to habitual food consumption in patients suffering a cerebrovascular event. Objective: To assess the influence of dietary habits as well as other lifestyle-related variables on the risk of suffering a stroke. Design: A case–control study was designed. Fifty-one cases (age: 59.1 ± 9.1y.o; BMI; 30.8 ± 3.4 kg/m2 ) and 51 controls (age: 61.1 ± 9.1y.o; BMI; 30.4 ± 3.6 kg/m2 ) were enrolled in the study. Anthropometric and body composition variables were measured. Dietary information was obtained from a validated food frequency questionnaire. Physical activity and lifestyle-related factors were assessed. Blood samples were drawn. Results: Patients suffering a stroke showed higher prevalence of diabetes (30 vs. 7.7%; P = 0.020) and hypertension (74.5 vs. 40.3%; P < 0.001) and were less physically active (36.7 vs. 66.6%; P = 0.024) than controls. Patients registered worse glucose and lipid profiles, higher levels of hepatic biomarkers, and higher blood cell counts than controls. Stroked patients showed lower adherence to a statistically derived healthy dietary pattern than controls (23.5 vs. 42.3%; P = 0.017). A logistic regression model was built up considering hypertension, diabetes, smoking, physical activity, adherence to a ‘healthy dietary pattern’ and C-reactive protein concentration. The final model strongly associated with the risk of suffering a stroke (R2 : 44.6%; Pmodel < 0.0001). Conclusion: Lifestyle variables such as physical activity, smoking habit, and a dietary pattern including foods with low inflammatory potential play an important role in the reduction of the risk of suffering a stroke.