Fight Aging!

Much of modern medical research is a matter of following chains of causation in our biology. Studies first uncover correlations between a particular protein and a medical condition, and then later work attempts to unpick the chain of signals and causative events in search of a first cause: protein A is behaving differently in disease Y because protein B is apparently doing something odd as well, and it can be shown that changing B directly changes A. It's already known that protein B interacts with protein C, and protein C leads to a well studied network of proteins, so some people start to look there as well for causative effects. There is a certain amount of searching for the keys under the lamp that takes place - established groups with their domain knowledge are always going to follow up when a new relationship touches on their area. Meanwhile, other researchers dive into the unknown darkness to find new relationships between the millions of distinct cogs and wheels of human biology.

It's a fearsomely complex business, and progress is very incremental. Each defensible new discovery in a chain of proteins and signaling mechanisms presents a point of opportunity at which some team somewhere will set up drug development. They are seeking a way to manipulate that link in the chain - that protein - to hopefully affect the disease process in a beneficial way, and perhaps do a little better than the drugs based on previously discovered links.

Here is an example of this sort of research, an investigation into the biochemistry of Parkinson's disease. Parkinson's is a neurodegenerative condition which might be considered a runaway example of one narrow mechanism of cell loss and damage - a process that takes place in all of our brains proceeds much faster in Parkinson's patients, leading to far greater loss of function. As to why this is the case ... well, scientists are still in search of that definitive answer.

After analyzing cells and post-mortem brain tissue from animals and humans, researchers noted that oxidative stress - a known culprit in neuron death - activated a protein called tyrosine kinase c-Abl in the nigra-striatum area of the brain. Neurons in this part of the brain are particularly vulnerable to Parkinson's injury.

Activation of this protein led to changes in another protein called parkin, which is known to be mutated in hereditary Parkinson's. The altered parkin lacked the capacity to break down other proteins, leading to harmful clumps of unprocessed protein in the neuron. The scientists believe this accumulation leads to progressive neuron death, resulting in Parkinson's symptoms that worsen over time.

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"When we blocked tyrosine kinase c-Abl activation, parkin function was preserved and neurons were spared," Dr. Imam said. "We believe these studies provide sound rationale for moving forward with a preclinical trial of tyrosine kinase c-Abl inhibitors, with the goal of developing a potent therapeutic drug for slowing the progression of Parkinson's."

If preclinical trials in animal models of Parkinson's disease yield positive results, the next step would be clinical trials in human patients, Dr. Imam said.

The accumulation of unwanted molecular waste in and around cells is a common theme in aging - and many diseases of aging involve an accelerated build up of one or more forms of damaging molecule. Without developing fundamentally new technologies to clear out these waste molecules on a regular basis, however, the most likely best that can be done through manipulation of our metabolism is to slow down the fall into a disease state. This is why greater support for bioremediation as a broad technology platform would be a good thing:

Bioremediation is the process of using plants and microorganisms (or aspects of their biochemistry) to restore a damaged or polluted environment. Medical bioremediation applies this same philosophy to the aging body - many aspects of aging can be thought of as having roots in damage and pollution at the level of our cells and cellular machinery.

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The most promising approach is to enable cells to break the junk down so that they don't fill up after all. This can be accomplished by equipping the lysosome with new enzymes that can degrade the relevant material. The natural place to seek such enzymes is in soil bacteria and fungi, as these aggregates, despite not being degraded in mammals, do not accumulate in soil in which animal carcasses are decaying, nor in graveyards where humans are decaying. This suggests that the micro-organisms present in soil have enzymes capable of breaking these aggregates down, and work now being carried on at Arizona State University, has already confirmed this analysis.