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Loss of Nfkb1 leads to early onset aging

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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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Differentially expressed genes and gene networks involved in pig ovarian follicular atresia

TL;DR: The present study enlists key upstream regulators in follicle atresia based on results and on a literature review and identifies novel gene candidates and gene networks identified to lead to a better understanding of the molecular regulation of ovarian follicular atResia.
Journal ArticleDOI

Epigenetic alterations in blood mirror age-associated DNA methylation and gene expression changes in human liver

TL;DR: Age-associated DNA methylation and expression changes in human liver that are partly reflected by epigenetic alterations in blood are identified and identified 151 genes whose liver expression also correlated with age.
Journal ArticleDOI

"Cell Membrane Theory of Senescence" and the Role of Bioactive Lipids in Aging, and Aging Associated Diseases and Their Therapeutic Implications.

Undurti N Das
TL;DR: In this article, it was shown that the deficiency of polyunsaturated fatty acids (PUFAs) may indicate malnutrition and deficiency of several minerals, trace elements and vitamins some of which are also much needed co-factors for the normal activity of desaturases.
References
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Journal ArticleDOI

Cellular senescence: when bad things happen to good cells

TL;DR: Understanding the causes and consequences of cellular senescence has provided novel insights into how cells react to stress, especially genotoxic stress, and how this cellular response can affect complex organismal processes such as the development of cancer and ageing.
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Clearance of p16 Ink4a -positive senescent cells delays ageing-associated disorders

TL;DR: Data indicate that cellular senescence is causally implicated in generating age-related phenotypes and that removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan.
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A DNA damage checkpoint response in telomere-initiated senescence

TL;DR: It is proposed that telomere-initiated senescence reflects a DNA damage checkpoint response that is activated with a direct contribution from dysfunctional telomeres.
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Senescent Cells, Tumor Suppression, and Organismal Aging: Good Citizens, Bad Neighbors

TL;DR: The senescence response may be antagonistically pleiotropic, promoting early-life survival by curtailing the development of cancer but eventually limiting longevity as dysfunctional senescent cells accumulate.
Journal ArticleDOI

The essence of senescence

TL;DR: The various features of cellular senescence are reviewed and their contribution to tumor suppression is discussed and the power and limitations of the biomarkers currently used to identify senescent cells in vitro and in vivo are highlighted.
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