Shc Signaling Adaptor Proteins

Publication Title: 
PLoS genetics

In Caenorhabditis elegans (C. elegans), the promotion of longevity by the transcription factor DAF-16 requires reduced insulin/IGF receptor (IIR) signaling or the ablation of the germline, although the reason for the negative impact of germ cells is unknown. FOXO/DAF-16 activity inhibits germline proliferation in both daf-2 mutants and gld-1 tumors. In contrast to its function as a germline tumor suppressor, we now provide evidence that somatic DAF-16 in the presence of IIR signaling can also result in tumorigenic activity, which counteracts robust lifespan extension.

Author(s): 
Qi, Wenjing
Huang, Xu
Neumann-Haefelin, Elke
Schulze, Ekkehard
Baumeister, Ralf
Publication Title: 
Free Radical Biology & Medicine

Steroid hormones exhibit diverse biological activities. Despite intensive studies on steroid function at the genomic level, their nongenomic actions remain an enigma. In this study, we investigated the role of reactive oxygen species (ROS) in androgen-stimulated prostate cancer (PCa) cell proliferation. In androgen-treated PCa cells, increased cell growth and ROS production correlated with elevated p66Shc protein, an authentic oxidase. This growth stimulation was blocked by antioxidants.

Author(s): 
Veeramani, Suresh
Chou, Yu-Wei
Lin, Frank C.
Muniyan, Sakthivel
Lin, Fen-Fen
Kumar, Satyendra
Xie, Yan
Lele, Subodh M.
Tu, Yaping
Lin, Ming-Fong
Publication Title: 
PLoS genetics

In Caenorhabditis elegans (C. elegans), the promotion of longevity by the transcription factor DAF-16 requires reduced insulin/IGF receptor (IIR) signaling or the ablation of the germline, although the reason for the negative impact of germ cells is unknown. FOXO/DAF-16 activity inhibits germline proliferation in both daf-2 mutants and gld-1 tumors. In contrast to its function as a germline tumor suppressor, we now provide evidence that somatic DAF-16 in the presence of IIR signaling can also result in tumorigenic activity, which counteracts robust lifespan extension.

Author(s): 
Qi, Wenjing
Huang, Xu
Neumann-Haefelin, Elke
Schulze, Ekkehard
Baumeister, Ralf
Publication Title: 
Methods in Molecular Biology (Clifton, N.J.)

Nutrient availability and nutrient-dependent biochemical signals represent major determinants of cellular senescence and organismal aging. The present chapter describes simple procedures to reliably evaluate the response of cultured cell to nutrients through the longevity protein p66(SHC1) and the mTOR/S6K cascade, which might be used to study cellular senescence and its chemical modulation by pharmaceutical agents in vitro.

Author(s): 
Ranieri, Sofia Chiatamone
Pani, Giovambattista
Publication Title: 
Scientific Reports

The physiological roles of the protease inhibitor SERPINB3 (SB3) are still largely unknown. The study was addressed to assess the biological effects of this serpin in vivo using a SB3 transgenic mouse model. Two colonies of mice (123 transgenic for SB3 and 148 C57BL/6J controls) have been studied. Transgenic (TG) mice showed longer survival than controls and the difference was more remarkable in males than in females (18.5% vs 12.7% life span increase). In TG mice decreased IL-6 in serum and lower p66shc in the liver were observed.

Author(s): 
Villano, Gianmarco
Ruvoletto, Mariagrazia
Ceolotto, Giulio
Quarta, Santina
Calabrese, Fiorella
Turato, Cristian
Tono, Natascia
Biasiolo, Alessandra
Cattelan, Arianna
Merkel, Carlo
Avogaro, Angelo
Gatta, Angelo
Pontisso, Patrizia
Publication Title: 
Pfl¸gers Archiv: European Journal of Physiology

Hyperinsulinemia and metabolic diseases are known to be associated with a reduction in life span. In the presence of insulin resistance, insulin signaling is selectively impaired, contributing to longevity shortening. Insulin indeed activates a complex web of intracellular downstream pathways, which are involved in mechanisms regulating longevity, primarily affecting cellular proliferation and apoptosis. Insulin resistance promotes reactive oxygen species (ROS) formation and favors a pro-inflammatory milieu, both these conditions playing a critical role in the reduction of life span.

Author(s): 
Avogaro, Angelo
de Kreutzenberg, Saula Vigili
Fadini, Gian Paolo
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