NF-κB Signaling in the Aging Process

Salminen, Antero; Kaarniranta, Kai

doi:10.1007/s10875-009-9296-6

Cited by 114 publications

(89 citation statements)

References 98 publications

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“…SIRT1 has been reported to deacetylate the lysine residues of a number of nuclear proteins, such as p53 (Yuan et al., 2011), NF‐κB (Salminen & Kaarniranta, 2009), PGC‐1a (Amat et al., 2009), CBP/p300 (Das, Lucia, Hansen & Tyler, 2009), and forkhead family proteins (Brunet et al., 2004). Several recent studies demonstrated that Sirt1 could inhibit TGF‐β signaling and ameliorate fibrosis (Huang et al., 2014; Kume et al., 2007; Zerr et al., 2014).…”

Section: Discussionmentioning

confidence: 99%

Activation of DNA demethylases attenuates aging‐associated arterial stiffening and hypertension

Chen

Sun

2018

Aging Cell

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Summary DNA methylation increases with age. The objective of this study was to investigate whether compound H, a potential activator of DNA demethylases, attenuates aging‐related arterial stiffness and hypertension. Aged mice (24–27 months) and adult mice (12 months) were used. Pulse wave velocity (PWV), a direct measure of arterial stiffness, and blood pressure (BP) were increased significantly in aged mice. Notably, daily treatments with compound H (15 mg/kg, IP) for 2 weeks significantly attenuated the aging‐related increases in PWV and BP. Compound H abolished aging‐associated downregulation of secreted Klotho (SKL) levels in both kidneys and serum likely by enhancing DNA demethylase activity and decreasing DNA methylation. Aging‐related arterial stiffness was associated with accumulation of stiffer collagen and degradation of compliant elastin which are accompanied by increased expression of MMP2, MMP9, TGF‐β1, and TGF‐β3. These changes were effectively attenuated by compound H, suggesting rejuvenation of aged arteries. Compound H also rescued downregulation of Sirt1 deacetylase, AMPKα, and eNOS activities in aortas of aged mice. In cultured smooth muscle cells (SMCc) Klotho‐deficient serum upregulated expression of MMPs and TGFβ which, however, was not affected by compound H. In conclusion, compound H attenuates aging‐associated arterial stiffness and hypertension by activation of DNA demethylase which increases renal SKL expression and consequently circulating SKL levels leading to activation of the Sirt1‐AMPK‐eNOS pathway in aortas of aged mice.

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Section: Discussionmentioning

confidence: 99%

Activation of DNA demethylases attenuates aging‐associated arterial stiffening and hypertension

Chen

Sun

2018

Aging Cell

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“…However, since rapamycin is a strong immunosuppressive drug (408) that, on the one hand, inhibits type-1 IFN (41), modulates T cell trafficking (345), and regulates expression of Foxp3 in Tregs (138,326), but on the other, upregulates and improves the quality of CD8 memory T cell differentiation (13), it is not yet clear how this feeding regimen impacts immune senescence. Given the counter regulatory role of NFkB in inhibiting autophagy, a cross-talk between the inflammatory and autophagy pathway is likely to occur, since inducers of autophagy such as FOXO3a and sirtuin 1 (SIRT1) can inhibit NFkB signaling (28,(315)(316)(317)(318) and enhance autophagic degradation. Increased inflammatory responses observed during advanced age and increased inflammatory disease onset and progression during aging may well be an outcome of this cross-talk.…”

Section: H Autophagy Aging and Immune Responsementioning

confidence: 99%

Aging and Immune Function: Molecular Mechanisms to Interventions

Ponnappan

2011

Antioxidants & Redox Signaling

279

266

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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 NFkB 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.

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“…13,14 Activated NF-kB translocation into the nucleus is associated with agerelated pathologies. 15 Previous studies showed that the transcriptional activity of NF-kB is regulated by SIRT6. SIRT6 can suppress the NF-kB activity by deacetylating the histone H3K9 of NF-kB dependent genes 16 as well as the Lys 310 (K310) of NF-kB p65 (RelA) subunit.…”

Section: Introductionmentioning

confidence: 99%

Calorie restriction-induced SIRT6 activation delays aging by suppressing NF-κB signaling

Zhang

et al. 2016

Cell Cycle

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Calorie restriction (CR) extends lifespan from yeast to mammals. SIRT6 is a member of the sirtuin family of NAD C -dependent histone deacetylases, which is responsible for mediating the effects of CR. The transcription factor NF-kB, which is involved in inflammation and aging, has been shown to be regulated by SIRT6. Here we describe the crucial role of SIRT6 in aging and inflammation. We show that CR had improved renal insufficiency and enhanced SIRT6 expression after 6-month treatment in aged mice. Culture cells in low glucose (LG) conditions also showed resistance to cell senescence and enhanced SIRT6 expression compared to normal glucose (NG) group, showing beneficial effects of the CR-mimic cultural conditions. Moreover, SIRT6 overexpression is sufficient to delay the replicative senescence of WI38 by attenuating NF-kB signaling, while SIRT6 knockdown results in accelerated cell senescence and overactive NF-kB signaling. These findings confirm the key status of CR and disclose the critical role of SIRT6 on aging and inflammation.

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NF-κB Signaling in the Aging Process

Cited by 114 publications

References 98 publications

Activation of DNA demethylases attenuates aging‐associated arterial stiffening and hypertension

Activation of DNA demethylases attenuates aging‐associated arterial stiffening and hypertension

Aging and Immune Function: Molecular Mechanisms to Interventions

Calorie restriction-induced SIRT6 activation delays aging by suppressing NF-κB signaling

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