Aging and immune function: molecular mechanisms to interventions.
Abstract The immune system of an organism is an essential component of the defense mechanism aimed at combating pathogenic stress. Age-associated immune dysfunction, also dubbed "immune senescence," manifests as increased susceptibility to infections, increased onset and progression of autoimmune diseases, and onset of neoplasia. Over the years, extensive research has generated consensus in terms of the phenotypic and functional defects within the immune system in various organisms, including humans. Indeed, age-associated alterations such as thymic involution, T cell repertoire skewing, decreased ability to activate naïve T cells and to generate robust memory responses, have been shown to have a causative role in immune decline. Further, understanding the molecular mechanisms underlying the generation of proteotoxic stress, DNA damage response, modulation of ubiquitin proteasome pathway, and regulation of transcription factor NFκB activation, in immune decline, have paved the way to delineating signaling pathways that cross-talk and impact immune senescence. Given the role of the immune system in combating infections, its effectiveness with age may well be a marker of health and a predictor of longevity. It is therefore believed that a better understanding of the mechanisms underlying immune senescence will lead to an effective interventional strategy aimed at improving the health span of individuals. Antioxid. Redox Signal. 14, 1551-1585.
Ponnappan
Subramaniam
S
Department of Geriatrics, University of Arkansas for Medical Sciences, 4301 W. Markham, Little Rock, AR 72205, USA.
Ponnappan
Usha
U
D000375:Aging; D000818:Animals; D004247:DNA / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000276:immunology*; D035683:MicroRNAs / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D016615:Telomere / Q000276:immunology
D035683:MicroRNAs; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D004247:DNA
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