Chronic inflammation, or "inflammaging," is a major driver of the aging process and is linked to age-related diseases like heart disease, Alzheimer’s, cancer, and diabetes.
But how does this work at the molecular level? Let’s break it down!
Key Molecular Mechanisms Behind Inflammaging:
Genomic Instability: DNA damage from aging increases pro-inflammatory signaling.
Telomere Attrition: Shortened telomeres trigger the p53 pathway, activating inflammatory responses.
Mitochondrial Dysfunction: Impaired mitochondria produce reactive oxygen species (ROS), leading to oxidative stress and promoting inflammation.
Cellular Senescence: Senescent cells release SASP (Senescence-Associated Secretory Phenotype) factors, like pro-inflammatory cytokines, which further fuel inflammation.
Altered Nutrient Sensing: Dysregulated nutrient sensing pathways, such as mTOR and insulin signaling, lead to metabolic inflammation.
Loss of Proteostasis: Misfolded proteins activate the unfolded protein response (UPR), contributing to chronic inflammation.
Dysbiosis: Imbalances in gut microbiota activate TLR4 and other immune pathways, exacerbating systemic inflammation.
These molecular changes create a feedback loop, driving both aging and inflammation.
Understanding these molecular mechanisms is key to developing therapies that can break the cycle of inflammaging, offering new pathways to treat age-related diseases and promote healthier aging.
Baechle, J. J., Chen, N., Makhijani, P., Winer, S., Furman, D., & Winer, D. A. (2023). Chronic inflammation and the hallmarks of aging. Mol Metab, 74, 101755. https://doi.org/https://doi.org/10.1016/j.molmet.2023.101755
Comments