SIRT1 longevity factor suppresses NF-kappaB -driven immune responses: regulation of aging via NF-kappaB acetylation?
The aging process involves changes in immune regulation, i.e. adaptive immunity declines whereas innate immunity becomes activated. NF-kappaB signaling is the master regulator of the both immune systems. Two recent articles highlight the role of the NF-kappaB system in aging and immune responses. Adler et al showed that the NF-kappaB binding domain is the genetic regulatory motif which is most strongly associated with the aging process. Kwon et al studying HIV-1 infection and subsequent immune deficiency process demonstrated that HIV-1 Tat protein binds to SIRT1 protein, a well-known longevity factor, and inhibits the SIRT1-mediated deacetylation of the p65 component of the NF-kappaB complex. As a consequence, the transactivation efficiency of the NF-kappaB factor was greatly potentiated, leading to the activation of immune system and later to the decline of adaptive immunity. These observations support the scenario where immune responses and aging process can be enforced by the potentiation of NF-kappaB transactivation efficiency. Longevity factors, such as SIRT1 and its activators, might regulate the efficiency of the NF-kappaB signaling, the major outcome of which is inflamm-aging via proinflammatory responses.
Salminen
Antero
A
Department of Neurology, Institute of Clinical Medicine, University of Kuopio, Finland. antero.salminen@uku.fi
Kauppinen
Anu
A
Suuronen
Tiina
T
Kaarniranta
Kai
K
D000107:Acetylation; D000375:Aging / Q000276:immunology*; D000818:Animals; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000276:immunology*; D051381:Rats; D015398:Signal Transduction / Q000276:immunology; D056564:Sirtuin 1; D037761:Sirtuins / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000276:immunology
D016328:NF-kappa B; D054322:tat Gene Products, Human Immunodeficiency Virus; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins