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Loss of Nfkb1 leads to early onset aging

TLDR
Data show that loss of Nfkb1 leads to early animal aging that is associated with reduced apoptosis and increased cellular senescence, and support the strong link between the NF-(B pathway and mammalian aging.
Abstract
NF-κB is a major regulator of age-dependent gene expression and the p50/NF-κB1 subunit is an integral modulator of NF-κB signaling. Here, we examined Nfkb1-/- mice to investigate the relationship between this subunit and aging. Although Nfkb1-/- mice appear similar to littermates at six months of age, by 12 months they have a higher incidence of several observable age-related phenotypes. In addition, aged Nfkb1-/- animals have increased kyphosis, decreased cortical bone, increased brain GFAP staining and a decrease in overall lifespan compared to Nfkb1+/+. In vitro, serially passaged primary Nfkb1-/- MEFs have more senescent cells than comparable Nfkb1+/+ MEFs. Also, Nfkb1-/- MEFs have greater amounts of phospho-H2AX foci and lower levels of spontaneous apoptosis than Nfkb1+/+, findings that are mirrored in the brains of Nfkb1-/- animals compared to Nfkb1+/+. Finally, in wildtype animals a substantial decrease in p50 DNA binding is seen in aged tissue compared to young. Together, these data show that loss of Nfkb1 leads to early animal aging that is associated with reduced apoptosis and increased cellular senescence. Moreover, loss of p50 DNA binding is a prominent feature of aged mice relative to young. These findings support the strong link between the NF-κB pathway and mammalian aging.

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Senescence-associated inflammatory responses: aging and cancer perspectives

TL;DR: It is proposed that controlling senescence-associated inflammation by targeting specific inflammatory mediators may have a beneficial therapeutic effect in treatment of cancer and aging-related diseases.
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Senescent cell clearance by the immune system: Emerging therapeutic opportunities.

TL;DR: The more that can be understood about the interplay between SCs and the immune system, the faster new interventions may be developed to delay, prevent, or treat age-related dysfunction and the multiple senescence-associated chronic diseases and disorders.
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NFKB1: a suppressor of inflammation, ageing and cancer.

TL;DR: Recent results reveal that the nuclear factor of kappa light polypeptide gene enhancer in B‐cells 1 (NFKB1) (p105/p50) subunit is an important regulator of NF‐κB activity in vivo, potentially revealing new strategies for targeting this pathway in inflammatory diseases and cancer.
References
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Journal ArticleDOI

Induction of transcriptional activity of AP-1 and NF-κb in the gastric mucosa during aging

TL;DR: The observation of increased activation of ERKs and JNK1 in the gastric mucosa of aged rats suggests a role for these MAPKs in regulating AP-1 and NF-kappaB transcriptional activity, which may be responsible for the age-related rise in Gastric mucosal proliferative activity.
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p50 (NF-κB1) Is an Effector Protein in the Cytotoxic Response to DNA Methylation Damage

TL;DR: The p50 subunit of NF-κB is identified as a central target in the response to O(6)-MeG and it is demonstrated that p50 is required for S(N)1-methylator-induced cytotoxicity.
Journal ArticleDOI

Age-related neural degeneration in nuclear-factor κB p50 knockout mice

TL;DR: Analysis of developmental degeneration changes in wild type and nuclear factor-κB p50 subunit knockout mice suggests that nuclear-factor κB may play an important role in neurovascular development, cell survival, and the aging process in the CNS.
Journal ArticleDOI

Development of spontaneous optic neuropathy in NF‐κΒp50‐deficient mice: requirement for NF‐κΒp50 in ganglion cell survival

TL;DR: The results show that p50 deficiency induced age‐related RGC death, indicating a new insight into the role of p50 in the pathophysiology of neuropathy, and further experiments with p50‐deficient mice may provide new targets for therapeutic intervention for human glaucoma.
Journal ArticleDOI

The c-Rel Subunit of NF-κB Regulates Epidermal Homeostasis and Promotes Skin Fibrosis in Mice

TL;DR: A role for p50 and c-Rel in regulating epidermal proliferation and homeostasis is revealed and a profibrogenic role for c- Rel in the skin is identified, and a link betweenEpidermal c-rel expression and systemic sclerosis is identified.
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