Sirtuins are a family of proteins that play critical roles in regulating cellular health and longevity.
They are known for their involvement in epigenetic regulation, meaning they can modify gene expression without altering the DNA sequence. Sirtuins also regulate chromatin structure, respond to environmental stress, and ensure the proper functioning of cellular processes such as the cell cycle, DNA repair, and mitochondrial energetics. Their activity is associated with aging and age-related diseases, making them a significant area of research in longevity and metabolic health.
Sirtuins and FoxO influence how cells remove waste.
Sirtuins significantly affect the activity of FoxO transcription factors through complex mechanisms. Sirtuins enhance FoxO activity, while factors stimulating insulin and IGF-1 receptors prevent FoxO activity. FoxO activation increases autophagy and the activity of the ubiquitin-proteasome system to cleanse cells of waste. Autophagy is the consumption of a cell’s organelles and is a programmed response to starvation, serving two main functions: it gets rid of cellular debris. It uses it to produce energy in the cell.
Aging is associated with accumulating excessively damaged proteins due to impaired proteasomal activity. This phenomenon is particularly evident in muscle, liver, and heart tissue. Moreover, abnormalities in proteasomal actions accelerate the development of neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. Therefore, activating sirtuins through FoxO effects on autophagy and the ubiquitin-proteasome system can help slow the progression of these age-related diseases.
Based on: https://doi.org/10.3389/fphys.2021.724506