Volt 2014 Abstract SECF
|Experimental basis for the “inflammaging” theory.|
Inflammaging involves a persistent pro-inflammatory state coursing with cardiac and energy metabolism alterations. This chronic, subclinical inflammatory process is directly related to the susceptibility increase of the elderly to the aging process itself. The recent discovery of the NFkB/mitochondria/NLRP3 connection during the innate immune response to inflammatory signals, leads us to explore this pathway and its relation with the hyperoxidative state of aging.
Three and eighteen months-old C57BL/6J mice were used. Mice were sacrificed and their hearts collected and processed immediately for mitochondrial respiration, or frozen to -80 °C. The expression and levels of key molecules involved in NF-kB/NLRP3 signaling pathways were analyzed by qRT-PCR and Western-blot, respectively; DNA-binding capacity of NF-κB p65 subunit was assessed by ELISA, and cytosolic oxidative stress was spectrophotometrically measured.
Our results show the existence of an enhanced basal proinflammatory status in aged mice, which was related to the both NLRP3 inflammasome and NF-kB innate immunity pathways activation. These changes were accompanied by a rise in pro-inflammatory cytokines (IL-1β, TNF-α), and enzymes (iNOS) expression, as well as a hyperoxidative state and mitochondrial failure. Moreover, inflammation was followed by the rise in the nuclear level and deacetylase activity of Sirtuin-1.
The results support NLRP3 inflammasome as a novel molecular signaling pathway during aging and identify it as a main target for the action of several anti-inflammatory and antioxidant agent. Furthermore, the results shows the importance of the chronic pro-inflammatory state during aging process.
• Keywords: aging, inflammasome NLRP3, Sirtuin-1
• O2k-Network Lab: ES Granada Acuna-Castroviejo D
Labels: MiParea: Respiration Pathology: Aging;senescence
Organism: Mouse Tissue;cell: Heart
HRR: Oxygraph-2k Event: Oral
1-Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de Granada, Avda. Del Conocimiento s/n, 18100 Armilla, Granada, Spain. 2-Departamento de Fisiología, Facultad de Medicina,Universidad de Granada, Avenida de Madrid 11, 18012 Granada, Spain. 3-Unidad de Gestión Clínica de Laboratorios Clínicos, Hospital Universitario San Cecilio, Avenida Dr. Olóriz s/n, 18012 Granada, Spain.
Supported by grants # PI08-1664; P07-CTS-03135 and PI13-00981