TLR4 polymorphisms and ageing: implications for the pathophysiology of age-related diseases.
BACKGROUND
Innate immunity provides a first line of host defense against infection by recognizing and killing microbes while simultaneously activating an instructive immune response. Toll-like receptors (TLRs) are principal mediators of rapid microbial recognition and function mainly by detection of pathogen-associated molecular patterns that do not exist in the host. Recognition of their ligands leads to a series of signaling events resulting in acute host responses, involved in killing pathogens.


CONCLUSIONS
We describe the involvement of TLR4 polymorphisms in ageing, and in particular in age-related diseases, suggesting the crucial role of molecules of innate immunity in pathophysiology of these diseases. Hence, we observed that pro-inflammatory alleles may be related to unsuccessful ageing, such as Alzheimer's disease, prostate cancer, and atherosclerosis; in contrast, the control of inflammation by anti-inflammatory alleles may result in increased longevity and successful ageing. Finally, a possible therapeutic approach to delay age-related diseases is outlined.
Balistreri
Carmela Rita
CR
Gruppo di Studio sull'Immunosenescenza, Dipartimento di Biopatologia e Metodologie Biomediche dell'Università di Palermo, Corso Tukory, Palermo, Italy. crbalistreri@unipa.it
Colonna-Romano
Giuseppina
G
Lio
Domenico
D
Candore
Giuseppina
G
Caruso
Calogero
C
D000375:Aging / Q000235:genetics* / Q000276:immunology; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007113:Immunity, Innate; D008136:Longevity / Q000235:genetics* / Q000276:immunology; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000276:immunology
D051197:Toll-Like Receptor 4