Researchers demonstrate interplay between metabolic health and healthy aging

Ribosomes, the cell's “translation factories,” are organelles that play a central role in protein synthesis, a process critical to all living organisms. These small structures are themselves composed of ribonucleic acid (RNA) and proteins and are essential for cell survival and normal function. This is because the proteins produced by these small structures are necessary for nearly every cellular process, including structure, function, and regulation.

Ribosome production begins when RNA polymerase I (Pol I) synthesizes pre-rRNA, the precursor transcript for mature ribosomal RNA (rRNA), which later becomes part of the ribosome. Previously, it was shown that lower Pol I activity is associated with a longer lifetime, but there was no precise explanation for this.

Research published in nature communications Here we demonstrate that reducing Pol I activity in the nematode Caenorhabditis elegans improves mitochondrial function and makes metabolism more stable, thereby extending lifespan. These findings also have implications for human aging.

In this study, Maria Ermolaeva's research group at the Fritz Lippmann Institute (FLI) at the Leibniz Institute for Aging in Jena, with its expertise in organismal and cellular metabolism and aging in terms of stress tolerance and homeostasis, and in Pol I transcription and ribosomal Experience in biosynthesis was combined. Professor in Holger Bierhoff's research group “Epigenetics of Aging''. The group is affiliated with Friedrich Schiller University Jena and also with FLI.

Together, rRNA biogenesis and ribosome biogenesis consume up to 60% of cellular energy. In this context, the team's findings support the idea that Pol I inhibition extends lifespan, healthspan, and metabolic fitness by actively lowering energy expenditure.

Interestingly, decreased Pol I activity not only generates an ATP surplus available for cellular quality control pathways, but also induces metabolic rewiring that suppresses triglyceride consumption and mitochondrial respiration. Mitochondrial respiration is an important source of reactive oxygen species (ROS) and mitochondrial damage during aging, so reducing this activity can have anti-aging effects.

The researchers also genetically engineered C. elegans to increase Pol I activity. Although these animals showed increased body size and neuromuscular performance and an early health advantage, their metabolism deteriorated more rapidly, leading to premature aging and early death. Ta. Finally, we showed that the ability to prolong life by reducing Pol I activity is not limited by aging and can provide benefits even in later life.

“Previous studies by us and others have determined that older age is a limiting factor in the effectiveness of commonly known interventions such as metformin and dietary restriction, making them more effective later in life. “It was very exciting for us to discover such a longevity intervention,” says Maria. Ermolaeva.

“It was also exciting to discover a geriatric protective intervention that works by actively suppressing energy metabolism. Studies in very long-lived species such as bowhead whales and naked mole rats have shown that their important We found that among these genetic advantages is a reduction in energy metabolism. Now, we have discovered an intervention that has the potential to replicate this positive trait in humans. ”

This finding may also be relevant to human aging, as the researchers also included human cells in their study. “Aging is a major risk factor for the development of cancer, and this is almost always associated with increased ribosome biogenesis,” says Holger Bierhoff. “Moderately reducing rRNA synthesis, especially in older adults, may be a viable option not only to improve metabolic health but also to reduce cancer risk,” he said. added.

Finally, this study shows that overconsumption of dietary protein, a common self-intervention that promotes muscle growth when combined with resistance exercise, has potential risks as it also stimulates Pol I activity. is emphasized. Similar to the results of the Pol I-enhanced C. elegans study, overconsumption of protein-rich foods and supplements may improve physical fitness in the short term, but in the long term it accelerates the metabolic aging process and increases the may inhibit organ function in the body. .

This study provides important insights into the molecular mechanisms underlying longevity. Targeted regulation of Pol I activity may open new avenues for the development of treatments that promote healthy aging.