Proto-Oncogene Proteins c-akt

Publication Title: 
Aging Cell

Dampening of insulin/insulin-like growth factor-1 (IGF1) signaling results in the extension of lifespan in invertebrate as well as murine models. The impact of this evolutionarily conserved pathway on the modulation of human lifespan remains unclear. We previously identified two IGF1R mutations (Ala-37-Thr and Arg-407-His) that are enriched in Ashkenazi Jewish centenarians as compared to younger controls and are associated with the reduced activity of the IGF1 receptor as measured in immortalized lymphocytes.

Author(s): 
Tazearslan, Cagdas
Huang, Jing
Barzilai, Nir
Suh, Yousin
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: 
Oncology Reports

SIRT1 is the human orthologue of SIR2, a conserved NAD-dependent protein deacetylase that regulates longevity in yeast and in Caenorhabditis elegans. Overexpression of SIRT1 in cancer tissue, compared with normal tissue, has been demonstrated, suggesting that SIRT1 may act as a tumor promoter. The function of SIRT1 in liver cancer has not been elucidated. In the present study, SIRT1 re-expression or knockdown was induced in hepatoma cell lines and liver normal cell lines.

Author(s): 
Wang, Hanning
Liu, Hao
Chen, Kaiyun
Xiao, Jinfeng
He, Ke
Zhang, Jinqian
Xiang, Guoan
Publication Title: 
Journal of Ethnopharmacology

ETHNOPHARMACOLOGICAL RELEVANCE: Eucommia ulmoides Oliv. Bark. (EUE), has commonly been used to fortify the muscles and lungs, lower blood pressure, prevent miscarriage, improve the tone of liver and kidneys, and promote longevity the traditional tonic medicines of Korea, China, and Japan. AIM OF THE STUDY: In this study, we investigated that the neuroprotective activities and possible mechanisms of EUE aqueous extract in hydrogen peroxide (H(2)O(2))-induced neuronal cell death in human SH-SY5Y neuroblastoma cells.

Author(s): 
Kwon, Seung-Hwan
Kim, Min-Jung
Ma, Shi-Xun
You, In-Jee
Hwang, Ji-Young
Oh, Ji-Hwan
Kim, Sun-Yeou
Kim, Hyoung-Chun
Lee, Seok-Yong
Jang, Choon-Gon
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: 
Tsitologiia

Kinase TOR (target of rapamycin), discovered as a target of antibiotic rapamycin, the evolutionarily conservative serine/threonine kinase that integrates numerous extra-cellular and intracellular signals, regulating cell growth, protein synthesis and metabolism. Mammalian kinase (mTOR) exists in two complexes: the rapamycin-sensitive TORC1 and rapamycin resistant mTORC2, controlling in the cell different programs.

Author(s): 
Zubova, S. G.
Shitikova, Zh V.
Pospelova, T. V.
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

Tumors use a wide array of immunosuppressive strategies, such as reducing the longevity and survival of dendritic cells (DCs), to diminish immune responses and limit the effect of immunotherapy. In this study, we found that tumors upregulate the expression of multiple microRNAs (miRNAs), such as miR-16-1, miR-22, miR-155, and miR-503. These tumor-associated miRNAs influenced the survival and longevity of DCs by affecting the expression of multiple molecules that are associated with apoptotic signaling pathways.

Author(s): 
Min, Siping
Liang, Xue
Zhang, Miaomiao
Zhang, Yuan
Mei, Shiyue
Liu, Jinzhe
Liu, Jingyi
Su, Xiaomin
Cao, Shuisong
Zhong, Xueqing
Li, Yueming
Sun, Jiatan
Liu, Qiaofei
Jiang, Xingran
Che, Yongzhe
Yang, Rongcun
Publication Title: 
Biochemical and Biophysical Research Communications

Cellular senescence is a tumor suppression mechanism. We previously reported that CKII downregulation induces senescence in human lung fibroblast IMR-90 and colon cancer HCT116 cells. In this study, potential longevity drugs, including rapamycin, vitamin C, and vitamin E, blocked CKII downregulation-mediated senescence through reduction of reactive oxygen species (ROS) production in HCT116 cells.

Author(s): 
Park, Ji Hye
Kim, Jin Joo
Bae, Young-Seuk
Publication Title: 
PloS One

There is increasing evidence that nutrient-sensing machinery is critically involved in the regulation of aging. The insulin/insulin-like growth factor-1 signaling pathway is the best-characterized pathway with an influence on longevity in a variety of organisms, ranging from yeast to rodents. Reduced expression of the receptor for this pathway has been reported to prolong the lifespan; however, the underlying mechanisms are largely unknown. Here we show that haploinsufficiency of Akt1 leads to an increase of the lifespan in mice.

Author(s): 
Nojima, Aika
Yamashita, Masakatsu
Yoshida, Yohko
Shimizu, Ippei
Ichimiya, Harumi
Kamimura, Naomi
Kobayashi, Yoshio
Ohta, Shigeo
Ishii, Naoaki
Minamino, Tohru
Publication Title: 
Blood Cells, Molecules & Diseases

The ability of hematopoietic stem cells (HSCs) to self-renew and differentiate into progenitors is essential for homeostasis of the hematopoietic system. The longevity of HSCs makes them vulnerable to accumulating DNA damage, which may be leukemogenic or result in senescence and cell death. Additionally, the ability of HSCs to self-renew and differentiate allows DNA damage to spread throughout the hematologic system, leaving the organism vulnerable to disease.

Author(s): 
Weiss, Cary N.
Ito, Keisuke

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