Role of TLR Polymorphisms in Aging and Age-Related Diseases

Innate immunity provides the first line of host defense against infection by recognizing and killing microbes, and simultaneously activating an instructive immune response. Toll-like receptors (TLRs) are principal mediators of rapid microbial recognition, and they mainly function by detecting exogenous pathogen-associated molecular patterns. Recognition of their ligands actives signaling ways, which culminate in evocating acute host responses, involved in killing pathogens. Here, we describe the involvement of TLR4 polymorphisms in aging, and particularly in immunosenescence and age-related diseases, suggesting the crucial role of molecules of innate immunity in the pathophysiology of these diseases. Accordingly, we observed that proinflammatory alleles may be related to unsuccessful aging, such as Alzheimer’s disease, prostate cancer, diabetes, cardiovascular diseases (i.e., atherosclerosis, aneurysm), and the anti-inflammatory alleles may reciprocally result in increased longevity and successful aging. Finally, a possible therapeutic approach to delay age-related diseases is outlined.