&amp;cestchinlong;Growing old with nuclear factor–κB

Giardina, Charles; Hubbard, Andrea K.

doi:10.1379/1466-1268(2002)007<0207:gownfb>2.0.co;2

Cited by 29 publications

(18 citation statements)

References 81 publications

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“…NF-κB activity increases with chronologic age in a variety of tissues of mammals (24)(25)(26)(27)(28). Thus, NF-κB activation could drive aging in response to time-dependent accumulation of cell damage.…”

Section: Discussionmentioning

confidence: 99%

NF-κB inhibition delays DNA damage–induced senescence and aging in mice

et al. 2012

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The accumulation of cellular damage, including DNA damage, is thought to contribute to aging-related degenerative changes, but how damage drives aging is unknown. XFE progeroid syndrome is a disease of accelerated aging caused by a defect in DNA repair. NF-κB, a transcription factor activated by cellular damage and stress, has increased activity with aging and aging-related chronic diseases. To determine whether NF-κB drives aging in response to the accumulation of spontaneous, endogenous DNA damage, we measured the activation of NF-κB in WT and progeroid model mice. As both WT and progeroid mice aged, NF-κB was activated stochastically in a variety of cell types. Genetic depletion of one allele of the p65 subunit of NF-κB or treatment with a pharmacological inhibitor of the NF-κB-activating kinase, IKK, delayed the age-related symptoms and pathologies of progeroid mice. Additionally, inhibition of NF-κB reduced oxidative DNA damage and stress and delayed cellular senescence. These results indicate that the mechanism by which DNA damage drives aging is due in part to NF-κB activation. IKK/NF-κB inhibitors are sufficient to attenuate this damage and could provide clinical benefit for degenerative changes associated with accelerated aging disorders and normal aging.

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Section: Discussionmentioning

confidence: 99%

NF-κB inhibition delays DNA damage–induced senescence and aging in mice

et al. 2012

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“…We speculate that the increased expression of immune response genes in aged animals may be a compensatory response to the age dependent decline in immune function. For example, the increased expression of MHC class I and MHC class II genes may be in compensation for the declined function of antigen presenting cells (Effros and Walford, 1984;Giardina and Hubbard, 2002;Plowden et al, 2004aPlowden et al, , 2004b, while the increased expression of immunoglobulin related genes may be in compensation for the reduced ability of B cells to produce high affinity antibodies (Lord et al, 2001;Han et al, 2004b).…”

Section: Discussionmentioning

confidence: 99%

Tissue specific and non-specific changes in gene expression by aging and by early stage CR

Hickey

Morrison

et al. 2006

Mechanisms of Ageing and Development

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Aging alters the expression of a variety of genes. Calorie restriction (CR), which extends life span in laboratory rodents, also changes gene expression. This study investigated changes in gene expression across 3 different tissues from the same mouse to examine how aging and early stage CR influence gene expression in different tissues of an organism. Expression profiling of heart, liver, and hypothalamus tissues was done in young (4-6 months) ad libitum fed (AL), young CR (2.5-4.5 months of CR), and old (26-28 months) AL male C57BL/6 mice. Aging significantly altered the expressions of 309, 1819, and 1085 genes in heart, liver, and hypothalamus tissues, respectively. In 9 genes, aging altered expression across all 3 tissues although the regulation directions did not agree across all 3 tissues for some genes. Early stage CR in young mice significantly changed the expressions of 192, 839, and 100 genes in heart, liver, and hypothalamus tissues, respectively, and 7 genes altered expression across all 3 tissues; 3 were up regulated and 4 were down regulated. The results of Gene Ontology (GO) Biological Process analysis indicated up regulation of antigen processing/presentation genes by aging and down regulation of stress response genes by early stage CR in all 3 tissues. The comparison of the results of aging and short term CR studies showed there were 389 genes, 18 GO biological processes, and 20 GO molecular functions in common.

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“…p53 and NF-κB are activated by other genotoxins, including ultraviolet light (UV) and reactive oxygen species (ROS), independently of ATM. Interestingly, hyperactivation of p53 promotes ageing (Maier et al, 2004) and hyperactivation of NF-κB is associated with ageing in mammals, leading to speculation that either of the transcription factors or the pathways that regulates them can drive ageing (Giardina and Hubbard, 2002).…”

Section: Dna Damage Responsementioning

confidence: 99%

“…NF-κB is activated by a variety of different types of genotoxic stress (Janssens and Tschopp, 2006). Furthermore, NF-κB is activated in numerous tissues of aged organisms (Giardina and Hubbard, 2002).…”

Section: Nf-κbmentioning

confidence: 99%

Signaling mechanisms involved in the response to genotoxic stress and regulating lifespan

Niedernhofer

Robbins

2008

The International Journal of Biochemistry & Cell Biology

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Ageing is defined by the loss of functional reserve over time, leading to a decreased capacity to maintain homeostasis under stress and increased risk of morbidity and mortality. Ageing is extremely heterogeneous between individuals and even between tissues within an organism, making it challenging to identify the molecular basis of ageing. Much of our current understanding of ageing comes from genetic studies in model organisms seeking genes that either accelerate or decelerate the ageing process. These studies revealed not only causes of ageing, but also signaling mechanisms that both promote and protect against ageing. In all cases, the signaling pathways that influence lifespan are familiar mechanisms that regulate cellular metabolism, growth, proliferation, differentiation and survival. This review highlights the significant overlap in signaling mechanisms implicated in both the cellular response to genotoxic stress and regulation of organism lifespan.

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&cestchinlong;Growing old with nuclear factor–κB

Cited by 29 publications

References 81 publications

NF-κB inhibition delays DNA damage–induced senescence and aging in mice

NF-κB inhibition delays DNA damage–induced senescence and aging in mice

Tissue specific and non-specific changes in gene expression by aging and by early stage CR

Signaling mechanisms involved in the response to genotoxic stress and regulating lifespan

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