The work confirmed that cells receive the signal that they have an excess, despite eating a normal diet, which causes organs such as the pancreas, liver and kidneys to function poorly and become inflamed. The study proposes that acting alone on inflammation can relieve symptoms and increase survival.
As reported by the academic institution, faced with a population that ages at an “accelerated” rate, it is essential to understand what happens in the body over time, on a molecular scale. It is known that the mTOR protein complex is involved in many processes, a “key” agent in multiple functions of the body and, especially, in metabolism.
This new work now finds in animal models that When mTOR activity increases, but only moderately, aging is accelerated, and the lifespan of animals can be shortened by up to 20 percent. Thus, aging is accelerated and life is shortened in animals whose cells “believe” they have too many nutrients, despite eating a normal diet.
Given the central role of mTOR in metabolism, this research provides “clues” to understand why aging-related diseases appear or worsen in people with high body mass index, an indicator related to obesity and inflammation.
It also provides information on why calorie restriction – a type of diet associated with greater longevity in animals – can promote healthy aging, since certain genes that are activated when restricting nutrient intake interact with mTOR.
In addition, a new research tool is created “to study the relationship between the increase in nutrients and the aging of different organs,” explained lead author Alejo Efeyan, head of the Metabolism and Cellular Signaling Group at the National Cancer Research Center ( CNIO).
The first author of the study is Ana Ortega-Molina, who currently directs her Laboratory of Metabolism in Cancer and Aging at the Severo Ochoa Molecular Biology Center (CBM), and collaborates with Rafael de Cabo, from the National Institute on Aging (NIA). ), in Bethesda, USA, Consuelo Borrás and Daniel Monleón, from the UV, and María Casanova-Acebes, head of the Cancer Immunity group at the CNIO.
Animals that “think” they eat 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 devised a system to “trick” mTOR, and thus be able to regulate its activity at will in animal models.
According to UV, the interior of cells is “a continuous coming and going of chemical signals, which are transmitted thanks to proteins” (of course cells also communicate with each other, with intercellular signals). The mTOR protein complex is a “key agent in the great highway of cellular communication involved in the use of energy, the metabolism of the cell.” mTOR is also known to influence longevity, although how is not yet well understood.
To manipulate the activity of mTOR at will, the CNIO team focused not on mTOR itself, but on the protein that must send it the signal indicating the amount of nutrients available in the cell.
The research team genetically modified this protein to make it lie and send the signal to mTOR that there are more nutrients in the cell than there really are.
Thus, the mTOR chemical signaling pathway is activated as if the animals were eating more, although in reality their diet does not change. When animals with this protein, which deceives mTOR, reach maturity, the functioning of the cells begins to fail and characteristic symptoms of aging are detected: the skin becomes thinner and damage appears in the pancreas, liver, kidneys and other organs.
The cells of the immune system come to repair them, but they are “overwhelmed” by the amount of damage, they accumulate and, instead of repairing, “they trigger inflammation that further increases the problems in these organs.”
16 years younger
The result of this vicious circle is that the lifespan of these animals in which mTOR works more than normal is shortened by 20 percent, which on the human scale would be equivalent to about 16 years.
The study sought to cut that circle by blocking the immune response that causes inflammation. The organ damage then improved enough to gain what in humans would be a few years of life.
For this reason, the study affirms that acting on chronic inflammation is “a potential therapeutic measure that controls the deterioration of health,” Ortega-Molina stressed.
According to UV, what happens when acting on the information received by mTOR, simulating an excess of nutrients, is reminiscent of a change typical of natural aging. The CNIO group compared their model with colonies of naturally aging mice, both their own and those from the National Institute on Aging (NIA).
For example, the activity of lysosomes, which are the organelles with which the cell eliminates and recycles its waste, is reduced in both naturally old animals and genetically modified ones. “When there is an excess of nutrients, it is logical that the cell turns off the recycling activity of the lysosomes, because this recycling is activated especially when there are no nutrients,” Efeyan clarified.
This decrease in lysosome activity also occurs in human aging, as verified by the UV group by contrasting blood samples from young people and septuagenarians. The University group has spent 20 years of research dedicated to the study of the molecular processes associated with aging, with the aim of designing effective strategies that promote healthy aging.
Consuelo Borrás and Daniel Monleón consider that “this type of collaborative studies lays the foundation for a better understanding of the role of nutrition in healthy aging and its relationship with nutritional interventions, such as caloric restriction or intermittent fasting.”
A new tool
Beyond this work, Efeyan considers that this new animal model offers “ample fertile ground to ask more questions about how the increase in nutrients, or their signaling, facilitates processes in different organs that allow us to understand their aging in particular.
Or, for example, investigate the relationship with neurodegenerative diseases, because there is some inflammation in the central nervous system. It is a tool that many more people will be able to use.”
Source: EUROPA PRESS
