The Hypoxic Response Versus Cellular Aggregates

If you've been following along for the past couple of years, you'll recall that one important part of aging is the build-up of damaging biochemicals both within and between our cells. These by-products of metabolism eventually grow to a level at which they greatly interfere with the functioning of our cells, tissues, and organs - or even kill us.

What we'd really like to see developed over the next decade or two is an outgrowth of the targeted nanotechnology, immune therapies, and viral therapies presently in the laboratory aimed at these aggregates. Given that we make it to 30 years of age without too much harm resulting, getting the build-up cleaned out every decade should prevent it from contributing to aging in any way.

Of course that's much easier to say than accomplish, and there are many, many different forms of unwanted biochemical involved in this part of the aging process. Fortunately for us, I think that the parallel labor of listing and then figuring out how to safely break down many different biochemicals is a task well suited to the years ahead, in which biotechnology becomes very cheap, and many new hands join the workforce.

Meanwhile, a wide range of potential strategies for attacking, slowing, or preventing the build up of specific biochemicals are emerging. I noted a couple not so long ago. Here's another recent line of work.

Survival mode that protects cells when oxygen is low also slows aging:

A cell's protective reaction to a drop in oxygen is called the hypoxic response. Researchers at the University of Washington (UW) have found that nematode worms live longer if their genetic make-up permits their cells to turn on the hypoxic response under normal oxygen conditions.


"The research findings suggest that the hypoxic response promotes longevity and reduces the accumulation of toxic proteins by a mechanism that is distinct from both dietary restriction and insulin-like signaling. It appears to be an alternative pathway, "Kaeberlein said. "However, we don't know if future studies might reveal that all of these different genetic pathways converge somewhere down the line into a common mechanism for delaying the effects of age."


The key factor that controls the hypoxic response is called HIF. HIF is regulated by another protein called VHL-1 ... animals lacking VHL-1 were resistant to the toxic proteins known to cause Alzheimer's disease and Huntington's diseases, and that their cells accumulated less of an age-pigment called lipofuscin. Lipofuscin is thought to be one indicator of an animal's health during aging. According to Kaeberlein, "these observations may suggest that the hypoxic response not only increases life span, but also lengthens health span and protects against the molecular processes that lead to neurodegenerative diseases in people".


The authors note that the hypoxic response, including HIF and VHL-1, is very well conserved in organisms from nematodes to humans, raising the possibility that modulating HIF activity may be useful for treating some age-associated diseases, and perhaps even slowing aging, in people.

Which is interesting, but assume that it's going to be a decade before a good answer emerges as to how this all hangs together. Meanwhile, researchers could be done with figuring out a way to break down lipfuscin safely on that same time scale - progress is all a question of research priorities, and at the present time all too few resources are directed towards turning what is known about aging into therapies that will enhance healthy longevity.


Hypoxia occurs in cyanide poisoning. Can a safe daily dose of amygdalin (vitamin B17) that can be found in bitter almonds produce this condition. Amydaline didn't work for cancer but maybe it can be a supplement that extends life. Could the consumption of a right amount of bitter almonds spread over a day be life-prolonging?

Posted by: braekmans herman at April 20th, 2009 5:19 AM

I can tell you that thinking at the level of "should I eat almonds" is a waste of time. If anything that trivial actually extended life, someone would have noticed over the past few thousand years. After you've ensured basic nutritional completeness in your diet, how much you eat and your level of exercise are the only thing that can be demonstrated to affect health and longevity in any significant way.

But of course the vast industry selling supplements and foods isn't going to tell you that, and has spent decades falsely educating people to think in terms of supplements. It's a false trail, a dead end, a red herring.

Stop wasting your time and focus on (a) calorie restriction, (b) exercise, (c) supporting research that will produce better results than (a) and (b).

Posted by: Reason at April 20th, 2009 9:51 AM
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