A Brace of Items of Interest

Some days there are more items of interest than I care to choose between; here are some that caught my eye today:

Does a component of niacin point the way to anti-aging drugs?

Using the techniques of structural biology, the Wistar team demonstrated that a component of the common vitamin B3, also known as niacin, binds to a specific site on the sirtuin molecule to inhibit its activity. This observation suggests that drugs designed to prevent the vitamin B3 component, nicotinamide, from binding at this site could have the effect of activating sirtuins. Any such drug would, in essence, inhibit the inhibitory effect of nicotinamide. As in mathematics, the two negatives would create a positive result – activation of sirtuins.

"Our findings suggest a new avenue for designing sirtuin-activating drugs," says Marmorstein. "The jury is still out as to whether a drug of this kind might result in longer life in humans, but I'm equally excited by the possibility that such interventions might help counteract age-related health problems like obesity and type II diabetes."

This is an insight into the way in which modern biotechnology can aid the search for more mechanisms of interest associated with any new discovery; it also illustrates the way in which any line item that is heavily funded (e.g. sirtuin research) will attract ever more funding around the peripheries. People flock to funded areas, as more conservative funding organizations tend to grant more readily to well-known, low-risk explorations. I leave it up the reader to decide whether this is a good thing or not; we're stuck with it either way, at least until human nature undergoes some radical change.

As I'm sure many of you know by now, I think this business of manipulating metabolism into a better mode of running is a poor path - the slow, expensive, low-yield way - to achieve meaningful results in enhanced longevity. Leave metabolism the way it is, and learn how to repair the accumulating damage that causes aging - that'll cost just as much time and money, and the results will be far more effective in terms of extending our healthy life spans.

Meanwhile, cancer and stem cell researchers continue to forge ahead with the tools of modern biotechnology - learn, and then turn that learning into a tool to strike at the problem. It's rare for a week to pass these days without the news of a new mechanism documented and understood:

Cold Spring Harbor Laboratory scientists discover new gene that prevents multiple types of cancer

Specifically, Mills' discovery identifies CHD5, a protein that prevents cancer, as a novel tumor suppressor, mapping to a specific portion of chromosome 1 known as 1p36. When CHD5 is not doing its job, the machinery within our cells that normally prevents cancer is switched off. The ability of CHD5 to function as a master switch for a tumor suppressive network suggests that this gene is responsible for a large number of diverse forms of human cancers. "CHD5 functions like a circuit breaker that regulates the tumor-preventing power in our cells - when it blows, cancer occurs," explains Mills. Modulation of CHD5 activity may provide novel strategies for better design of more effective cancer therapies.

...

The findings of Mills' study will influence the future of cancer research. It shows that deletion of a part of 1p36 causes cancer and increased "dosage" of CHD5 triggers extra tumor suppression. One extra dose, or copy, caused cells to either stop dividing or to undergo cell suicide by switching on a battery of potent tumor protective machinery. This work indicates that pharmaceuticals that switch on CHD5 may provide a way to treat many types of human cancer.

New protein inhibitor impedes growth of cancerous cells

Because cancer cells are typically fast growing and can mutate to adapt to new growth conditions, effective drug-based therapies will likely succeed in part by impeding multiple functions required for cell division and survival. One particular class of proteins, known as kinases, is known to play especially critical roles in the division of healthy cells, and appears to also be important for cell division in cancer cells, even though these cells are diseased and have lost some of the restraints on division that normal cells impose on themselves. Because central aspects of cell division are under the control of just a few key kinases, these proteins represent potentially important targets for new cancer therapeutics, but few if any effective inhibitors have been identified as acting specifically and effectively against one particular cell-division kinase, known as Plk1.

In the new work, Steegmaier et al. isolated a chemical compound, which they term BI 2536, that they demonstrate to be a potent inhibitor of Plk1, and show that BI 2536 can indeed effectively halt the growth of cancerous cells, both in cell culture and in an animal model for human tumor growth. BI 2536 caused growth arrest and cell death in cell lines derived from a variety of human cancers, and it inhibited the growth of human tumor grafts in mice, resulting in the death of tumor cells and regression of large tumors. The authors report that BI 2536 has now been brought into use in clinical studies of patients with locally advanced or metastatic cancers in order to address the therapeutic potential of the compound.

Master switches found for adult blood stem cells

Johns Hopkins Kimmel Cancer Center scientists have found a set of "master switches" that keep adult blood-forming stem cells in their primitive state. Unlocking the switches' code may one day enable scientists to grow new blood cells for transplant into patients with cancer and other bone marrow disorders.

The scientists located the control switches not at the gene level, but farther down the protein production line in more recently discovered forms of ribonucleic acid, or RNA. MicroRNA molecules, once thought to be cellular junk, are now known to switch off activity of the larger RNA strands which allow assembly of the proteins that let cells grow and function.

"Stem cells are poised to make proteins essential for maturing into blood cells, but microRNAs keep them locked in their place"

It's a revolution out there, as you may have noticed; the next few decades will see an explosion of knowledge and technology to better the human condition. But that won't be enough to greatly extend our healthy life spans - as opposed to a slow, incidental lengthening through advances across the board in medical technology - without far more interest and investment in the most efficient, direct paths to making rejuvenation a reality. It would be a real shame if we missed this golden opportunity to see a great deal more of the future in good health and vigor.

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