MAP Kinase Kinase Kinases

Publication Title: 
Age (Dordrecht, Netherlands)

The pathways that regulate energy homeostasis, the mechanisms of damage repair, and the signaling response to internal environmental changes or external signals have been shown to be critical in modulating lifespan of model organisms and humans. In order to investigate whether genetic variation of genes involved in these pathways contribute to longevity, a two-stage case-control study in two independent sets of long-lived individuals from Calabria (Italy) was performed. In stage 1, 317 SNPs in 104 genes were analyzed in 78 cases (median age 98 years) and 71 controls (median age 67 years).

Di Cianni, Fausta
Campa, Daniele
Tallaro, Federica
Rizzato, Cosmeri
de Rango, Francesco
Barale, Roberto
Passarino, Giuseppe
Canzian, Federico
Gemignani, Federica
Montesanto, Alberto
Landi, Stefano
Rose, Giuseppina
Publication Title: 
Cell Cycle (Georgetown, Tex.)

Here I overview the accompanying three reports on suppression of cellular senescence with inhibitors of mTOR, PI-3K and MEK. How can growth inhibitors suppress senescence? May these aging-suppressants decelerate organismal aging? To answer these questions, we need to reconsider the meaning of aging.

Blagosklonny, Mikhail V.
Publication Title: 
Cancer Research

Patients with chronic inflammatory bowel disease have a high risk of colon cancer. The molecules that initiate and promote colon cancer and the cancer pathways altered remain undefined. Here, using in vitro models and a mouse model of colitis, we show that nitric oxide (NO) species induce retinoblastoma protein (pRb) hyperphosphorylation and inactivation, resulting in increased proliferation through the pRb-E2F1 pathway.

Ying, Lei
Hofseth, Anne B.
Browning, Darren D.
Nagarkatti, Mitzi
Nagarkatti, Prakash S.
Hofseth, Lorne J.
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

Exercise/joint mobilization is therapeutic for inflammatory joint diseases like rheumatoid and osteoarthritis, but the mechanisms underlying its actions remain poorly understood. We report that biomechanical signals at low/physiological magnitudes are potent inhibitors of inflammation induced by diverse proinflammatory activators like IL-1beta, TNF-alpha, and lipopolysaccharides, in fibrochondrocytes.

Madhavan, Shashi
Anghelina, Mirela
Sjostrom, Danen
Dossumbekova, Anar
Guttridge, Denis C.
Agarwal, Sudha
Publication Title: 

Transforming growth factor-beta (TGF-β) has a dual role in epithelial malignancies, including head and neck squamous cell carcinoma (HNSCC). Attenuation of canonical TGF-β signaling enhances de novo tumor development, whereas TGF-β overexpression and signaling paradoxically promotes malignant progression. We recently observed that TGF-β-induced growth arrest response is attenuated, in association with aberrant activation of nuclear factor-κB (NF-κB), a transcription factor, which promotes malignant progression in HNSCC.

Freudlsperger, C.
Bian, Y.
Contag Wise, S.
Burnett, J.
Coupar, J.
Yang, X.
Chen, Z.
Van Waes, C.
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