NF-κB activation with aging: characterization and therapeutic inhibition.
Aging is a condition characterized by progressive decline in tissue homeostasis due, at least in part, to the accumulation of replicative, oxidative, and genotoxic stress over time. The activity of the transcription factor NF-κB is upregulated in both naturally aged mice and multiple progeroid mouse models of accelerated aging. Suppressing NF-κB activity genetically or pharmacologically has been shown to delay the onset and progression of aging pathology and therefore prolong the healthspan in progeroid mouse models. Here, we describe the methods for measuring aging endpoints along with NF-κΒ activation in mice, as well as after pharmacologic intervention to prevent NF-κB activation using a NEMO-binding domain (NBD)-protein transduction domain (PTD) fusion peptide.
Department of Metabolism and Aging, The Scripps Research Institute, 130 Scripps Way, #3B3, Jupiter, FL, 33458, USA.
Jing
J
Zhao
Xuesen
X
Li
Sara
S
McGowan
Laura J
LJ
Niedernhofer
Paul D
PD
Robbins
D000375:Aging / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D015415:Biomarkers; D004268:DNA-Binding Proteins / Q000172:deficiency; D004720:Endonucleases / Q000172:deficiency; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D017930:Genes, Reporter; D007150:Immunohistochemistry / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D054730:Protein Interaction Domains and Motifs; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism
D015415:Biomarkers; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C467063:NBD peptide, mouse; C514981:NEMO protein, mouse; D016328:NF-kappa B; D010455:Peptides; D011993:Recombinant Fusion Proteins; D051996:Transcription Factor RelA; D004720:Endonucleases; C499360:Ercc1 protein, mouse