ABSTRACT
Tissue regeneration is a highly coordinated process with sequential events including immune cell infiltration, clearance of damaged tissues, and immune-supported regrowth of the tissue. Aging has a well-documented negative impact on this process globally; however, whether changes in immune cells per se are contributing to the decline in the body's ability to regenerate tissues with aging is not clearly understood. Here, we set out to characterize the dynamics of macrophage infiltration and their functional contribution to muscle regeneration by comparing young and aged animals upon acute sterile injury. Injured muscle of old mice showed markedly elevated number of macrophages, with a predominance for Ly6Chigh pro-inflammatory macrophages and a lower ratio of the Ly6Clow repair macrophages. Of interest, a recently identified repair macrophage-derived cytokine, growth differentiation factor 3 (GDF3), was markedly downregulated in injured muscle of old relative to young mice. Supplementation of recombinant GDF3 in aged mice ameliorated the inefficient regenerative response. Together, these results uncover a deficiency in the quantity and quality of infiltrating macrophages during aging and suggest that in vivo administration of GDF3 could be an effective therapeutic approach.
Subject(s)
Aging/pathology , Growth Differentiation Factor 3/administration & dosage , Growth Differentiation Factor 3/pharmacology , Muscle, Skeletal/injuries , Muscle, Skeletal/physiopathology , Regeneration/drug effects , Acute Disease , Aging/drug effects , Animals , Cell Differentiation/drug effects , Kinetics , Male , Mice , Muscle, Skeletal/drug effects , Myoblasts/drug effects , Myoblasts/metabolism , Myoblasts/pathology , PhenotypeABSTRACT
Introducción. La innovación ha marcado el progreso de la cirugía por medio del desarrollo y aplicación de procedimientos seguros y rentables enfocados en solucionar los problemas del profesional. Además, ofrece a los usuarios nuevas técnicas y alternativas accesibles y seguras para elegir. División de temas tratados. La innovación en cirugía se basa en: 1) técnicas; 2) mejora en la logística de la práctica; 3) e introducción, diseño de dispositivos y herramientas. El Innovar debe estructurarse basado en marcos propuestos como el Idea, Development, Exploration, Assessment, Long term study (IDEAL). Hay que comprender la necesidad de innovar en cirugía y proponer puntos clave para tener en cuenta durante la implementación del marco IDEAL, herramienta valiosa como propuesta innovadora de cirugía en Latinoamérica. Conclusiones. La innovación es un camino al progreso y avance de la medicina en general. Se propone que para lograr un impacto innovador se centre en la aplicación del algoritmo propuesto, relacionándolo con la realidad que afronta nuestra sociedad Latinoamericana.
Introduction. Innovation has driven progress in surgery through the development and application of safe and profitable procedures that focus on solving the professional's problems. It also offers users new choices of safe and accessible techniques and alternatives. Division of Covered Topics. Innovation in surgery is based on 1) techniques; 2) improved logistics in the practice, and 3) the design and introduction of devices and tools. Innovation should be structured in frameworks such as those proposed by IDEAL (Idea, Development, Exploration, Assessment, Long term study). It is necessary to understand the need to innovate in surgery and to propose key aspects to take into consideration during the implementation of the IDEAL framework, which represents a valuable tool for the development of innovative proposals in Latin America. Conclusions. Innovation is a path towards progress and the advancement of medicine in general. It is suggested that innovative impact can be achieved by using the proposed algorithm, associating it with the realities we face in Latin America.
Introdução. A inovação tem marcado o avanço da cirurgia através do desenvolvimento e aplicação de procedimentos seguros e rentáveis com foco na solução dos problemas do profissional. Além disso, ofrece aos usuários novas técnicas e alternativas acessíveis e seguras para escolher. Divisão dos tópicos abordados. A inovação em cirurgia baseia-se em: 1) técnicas; 2) melhoria na logística da prática; e 3) introdução, design de dispositivos e ferramentas. Inovar deve ser estruturado com base em estruturas propostas, tais como Idea, Development, Exploration, Assessment, Long term study (IDEAL). É preciso entender a necessidade de inovar na cirurgia e propor pontos-chave a serem considerados na implantação da estrutura IDEAL, uma ferramenta valiosa como proposta inovadora da cirurgia na América Latina. Conclusões. A inovação é um caminho para o progresso e avanço da medicina em geral. Propõe-se que, para alcançar um impacto inovador, se concentre na aplicação do algoritmo proposto, relacionando-o com a realidade que enfrenta nossa sociedade Latino-americana.