The tissues of the human body adjust the intensity with which they eliminate waste based on their metabolic activity and, therefore, on the amount of waste they generate. This is concluded by a study led by Spanish researchers from the National Center for Cardiovascular Research (CNIC) and Pompeu Fabra University (UPF) in Barcelona, along with other institutions.
The study, also coordinated by scientists from the University of California in San Francisco (UCSF) and Yale University (USA), demonstrates that tissues with greater energy needs concentrate large cleaning teams formed by macrophages, immune system cells specialized in the removal of debris. It also confirms that the size of these teams increases in proportion to the metabolic activity of the tissue and the amount of waste it generates.
The research, published in the specialized journal "Science Immunology," has among its main authors the CNIC researcher Andrés Hidalgo. This scientist details that an important part of the waste is composed of damaged mitochondria, the organelles that act as "power plants" of the cells by transforming nutrients into usable energy.
"As mitochondria deteriorate while keeping cells functioning, they are discarded," he explains, adding that "the greater the energy demand of a tissue, the more mitochondria end up in the trash." To verify this, the team tracked the mitochondria in cardiac muscle, skeletal muscle, and brown fat of mice, observing that aged mitochondria ended up accumulating inside macrophages.
A key cleaning system for tissue performance
In a second phase, the researchers blocked the ability of macrophages to eliminate this waste. The system then stopped functioning properly: the heart reduced its pumping capacity, skeletal muscle lost strength, and brown fat decreased its heat production. Based on these results, the UPF professor and also the main co-author of the study, Pura Muñoz-Cánoves, concludes that "tissues need to stay clean to function at full capacity."
To unravel the origin of this cleaning mechanism, the team traced the process back to structural cells called fibroblasts, whose number increases in parallel with the mitochondrial activity of the tissue. These cells emit a signal that induces the proliferation of macrophages, allowing each tissue to adjust the size of its cleaning team to the amount of waste it produces.
The work also includes the analysis of data from human muscles, which confirms that the number of macrophages increases in parallel with the mitochondrial activity of the muscle, used as an indicator of its level of activity. The member of the Cardiovascular Research Institute of UCSF and senior author of the study, José Ángel Nicolás-Ávila, emphasizes that "this balance between the high energy demands of tissues and the number of macrophages seems to be fundamental" for maintaining health.
"The metabolism of tissues, the accumulation of waste, and the number of macrophages change with aging," points out the first author and member of UCSF, Laura Pena-Couso, who notes that these results "reveal the signals that connect these processes." Furthermore, she considers that "they open the possibility that acting on this system could help preserve the function of our tissues as we age."