Cure Aging or Die Trying

Telomerase seems to increase the cancer risk among mice, but what about men. People seem willing to try anything except consuming balanced meals with fruits and vegetables.


Before We Can Add Years to Life, We Must Add Life to Years from Jeriaska on Vimeo.

Tomás-Loba A, Flores I, Fernández-Marcos PJ, Cayuela ML, Maraver A, Tejera A, Borrás C, Matheu A, Klatt P, Flores JM, Viña J, Serrano M, Blasco MA.

Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre CNIO, Madrid, Spain.

Telomerase confers limitless proliferative potential to most human cells through its ability to elongate telomeres, the natural ends of chromosomes, which otherwise would undergo progressive attrition and eventually compromise cell viability. However, the role of telomerase in organismal aging has remained unaddressed, in part because of the cancer-promoting activity of telomerase. To circumvent this problem, we have constitutively expressed telomerase reverse transcriptase (TERT), one of the components of telomerase, in mice engineered to be cancer resistant by means of enhanced expression of the tumor suppressors p53, p16, and p19ARF. In this context, TERT overexpression improves the fitness of epithelial barriers, particularly the skin and the intestine, and produces a systemic delay in aging accompanied by extension of the median life span. These results demonstrate that constitutive expression of Tert provides antiaging activity in the context of a mammalian organism.

Astragalus saponins (AST) modulate mTOR and ERK signaling with
NF-kappa B as target in native and cytokine-induced HT-29 colon
cancer cells

J.K.S. Ko1, N.L. Mok1, C.M. Wong1, K.K.W. Auyeung1. 1Hong Kong
Baptist University, School of Chinese Medicine, Hong Kong, Hong Kong

Background: The total saponins of Astragalus membranaceus (AST)
possess potential anti-tumorigenic effects in human colon cancer cells
and tumor xenograft (Carcinogenesis 28:1347–1355, 2007). In the present
study, the proapoptotic effects of AST were investigated in native or TNFalpha
treated HT-29 cells to further unveil its mechanism of action.
Materials and Methods: The growth-inhibitory action of AST (60 mg/ml)
was evaluated in HT-29 cells using MTT viability assay. For cytokineinduced
cells, TNF-a (5 ng/ml) was added 1 h following AST treatment.
Western immunoblotting had been used to assess the protein expression
of apoptotic and transcription factors. Electrophoretic mobility shift assay
was conducted to reveal NF-kappa B DNA binding activity. Modulation of
cell proliferation by phase-specific cycle arrest was tested by flow cytometry.
Apoptotic analysis and detection of NF-kappa B subunit translocation were
determined by immunofluorescence nuclear staining.

Herbal (Astragalus) saponins inhibit HepG2 cell growth and promote apoptosis through NF- B and ERK signaling

Joshua Ko and Kathy Auyeung
Hong Kong Baptist University, Hong Kong, Hong Kong

We have recently reported that the total saponins of the Chinese medicinal herb Astragalus membranaceus (AST) possess promising anti-tumorigenic effects in human colon cancer cells and tumor xenograft through inhibition of cell proliferation and promotion of apoptosis (Carcinogenesis 28:1347-1355, 2007). In the present study, the anti-carcinogenic effects of AST were further studied in HepG2 human hepatocellular carcinoma cells. We focused on the involvement of both extracellular signal-regulated kinases (ERK) and nuclear factor-kappa B (NF- B) signaling pathways in AST-induced apoptosis. Our results have shown that AST could suppress HepG2 cell growth, while at the same time downregulate expression of the liver tumor marker -fetoprotein. Furthermore, apoptosis was induced through caspase 3 activation and subsequent poly(ADP-ribose) polymerase (PARP) cleavage, leading to the appearance of nuclear chromatin condensation. Besides, downregulation of the anti-apoptotic proteins bcl-2 and bcl-xL were also observed following AST treatment. In order to unveil the underlying mechanism of action, DNA binding activity of the transcription factor NF- B was examined by electrophoretic mobility shift assay. Data have demonstrated that NF- B DNA binding activity was significantly decreased after AST treatment. On the other hand, expression of the phosphorylated form of ERK was found to be prominently increased in a dose-dependent manner. Pretreatment of PD98059, a strong inhibitor of ERK, facilitated the cleavage of PARP, indicating an active involvement of the ERK signaling pathway in AST-induced apoptotic activity. Taken together, our findings suggest that AST has the potential to be developed as an effective chemotherapeutic agent in treating liver cancers, with known molecular targets and precise mechanism of action.