Study shows excess nutrients accelerate aging

Investigation CNIO And University of Valencia published in the journal Nature Aging, found that Cells that perceive excess nutrients accelerate aging and shorten life. The work proved that cells receive a signal that they have excess despite normal nutrition, causing organs such as the pancreas, liver and kidneys to function poorly and become inflamed. The study suggests that targeting inflammation alone may improve symptoms and increase survival.

According to the academic institution, Faced with a population that is aging at an “accelerated” rate, it is important to understand what is happening in the body over time. at the molecular level. It is known that the mTOR protein complex is involved in many processes and is a “key” agent in many body functions and, especially, in metabolism. This new work has now found in animal models that when mTOR activity is increased, but only moderately, aging is accelerated and animal lifespan can be shortened by up to 20%. Thus, aging is accelerated and life is shortened in animals whose cells “believe” they have too many nutrients, despite eating normally.

Given the central role of mTOR in metabolism, This study provides clues to why diseases associated with aging appear or worsen in people with a high body mass index, a measure associated with obesity and inflammation. It also provides information about why calorie restriction (a type of diet associated with increasing lifespan in animals) may promote healthy aging, because certain genes that are activated by nutrient restriction interact with mTOR.

In addition, a new research tool is being created “to study the relationship between increased amounts of nutrients and aging of various organs“explained the lead author Alejo Efeyan, Head of the Metabolism and Cell Signaling Group at the National Center for Cancer Research (CNIO). The study’s first author is Ana Ortega-Molina, who currently directs her Laboratory of Metabolism in Cancer and Aging at the Severo Ochoa Center for Molecular Biology (CBM) and collaborates with Rafael de Cabo of the National Institute on Aging (NIA). .), in Bethesda, USA, Consuelo Borras and Daniel Monleon from UF, as well as Maria Casanova-Acebes, leader of the Cancer Immunity Group at CNIO.

ANIMALS WHO “BELIEVE” THERE IS MORE

The activity of the mTOR protein complex is regulated depending on the amount of nutrients available in the cell. The authors of this study developed a system to trick mTOR and thus be able to regulate its activity at will in animal models. According to UV, the inside of cells is a “continuous coming and going of chemical signals that are transmitted by proteins” (of course, cells also communicate with each other through intercellular signals). The mTOR protein complex is “a key agent in the great highway of cellular communication involved in energy use and cell metabolism.” mTOR is also known to influence lifespan, although how this is not yet entirely clear.

To manipulate mTOR activity at will, the CNIO team focused not on mTOR itself, but on a protein that would send it a signal indicating the amount of nutrients available in the cell. The research team genetically modified this protein to tell it to lie and send a signal to mTOR that there are more nutrients in the cell than there actually are. Thus, the mTOR chemical signaling pathway is activated as if the animals were eating more, although in fact their diet does not change.

When animals with this mTOR spoofing protein reach adulthood, cell function begins to deteriorate and the characteristic symptoms of aging appear: The skin becomes thinner, damage to the pancreas, liver, kidneys and other organs appears. Immune system cells come to repair them, but they are “overwhelmed” by the amount of damage, accumulate and instead of repairing, “cause inflammation, which further increases the problems in these organs.”

SIXTEEN YEARS LESS

The result of this vicious cycle is that the lifespan of these animals, in which mTOR is working more than usual, is reduced by 20 percent, which on a human scale would be equivalent to about 16 years. The study sought to break this cycle by blocking the immune response that causes inflammation. The organ damage then improved enough to extend a person’s life by several years. For this reason, the study confirms that targeting chronic inflammation is “a potential therapeutic intervention that controls deterioration in health,” Ortega-Molina emphasized.

According to UV, what happens when mTOR-received information is exposed to mimic nutrient excess resembles the changes typical of natural aging. The CNIO team compared their model to colonies of naturally aging mice, both their own and National Institute on Aging (NIA) mice. For example, the activity of lysosomes—the organelles through which a cell removes and processes its waste—is reduced in both naturally aged animals and genetically modified ones. “When there is an excess of nutrients, it is logical that the cell turns off the recycling activity of lysosomes, because this recycling is activated especially when there are no nutrients,” Efeyan said.

This decrease in lysosome activity also occurs during human aging, which was confirmed by the UV group by contrasting blood samples from young people and septuagenarians. The university team has conducted 20 years of research to understand the molecular processes associated with aging, with the goal of developing effective strategies to promote healthy aging. Consuelo Borras and Daniel Monleon believe that “this type of collaborative research lays the foundation for a better understanding of the role of nutrition in healthy aging and its relationship to nutrition interventions such as calorie restriction or intermittent fasting.”

NEW TOOL

Beyond this work, Efeyan believes this new animal model offers “ This is fertile ground for us to ask more questions about how increasing nutrient availability or signaling facilitates processes in various organs that allow us to understand their aging. in particular. Or, for example, explore the connection with neurodegenerative diseases, because there is some kind of inflammation in the central nervous system. It’s a tool that a lot more people can use.”