RNA Polymerase I (Pol I) plays a crucial role in the intricate regulatory mechanisms that govern the balance between growth and longevity in response to nutrient availability. It is primarily responsible for transcribing a significant portion of RNA, crucial for processes such as protein synthesis. Lowering Pol I activity has been linked to extending lifespan in short-lived species, including nematode worms.
The interplay between insulin/insulin-like growth factor signaling (IIS), mechanistic target of rapamycin (mTOR), adenosine monophosphate-activated protein kinase (AMPK), and sirtuin pathways influences Pol I-mediated transcription of ribosomal RNA genes into pre-rRNA. This process is essential for cellular activities that demand high energy levels, such as mRNA translation.
Recent studies have shown that manipulating rRNA synthesis can have pro-longevity effects by affecting the nucleolus structure in organisms like C. elegans and D. melanogaster. By reducing Pol I activity, metabolic costs are decreased, promoting longevity by enhancing energy balance and metabolic flexibility.
Our research delves deeper into how limiting Pol I activity reshapes the lipidome and preserves mitochondrial function in nematode worms, extending lifespan. This intervention not only improves energy homeostasis but has also shown benefits in human primary cells. Additionally, restricting Pol I activity has proven to be more effective in extending lifespan compared to directly inhibiting protein synthesis, and it remains beneficial even when initiated later in life.
Link: https://doi.org/10.1038/s41467-024-46037-w
