World Health Organization

On Friday 17th April 2009 you could attend a one day course at Aston University on drug metabolism.

Drug metabolism exerts a powerful influence on drug action - from complete failure of a drug’s effectiveness to life-threatening toxicity. This course focuses on the aims, responses and processes of human drug biotransformation systems. As a result, it will assist health care professionals - particularly new prescribers (e.g. nurses, podiatrists or optometrists) to develop their drug therapy practices.

It’s hosted by Prof Michael Coleman, who combines academia with being cool and witty in equal measure.

This is more common than you think, although superglue is the usual culprit.

Paula Griffin, 29, squirted the hazardous liquid into her right eye by mistake after waking up with blurred vision.

Her eye was glued shut for eight hours and was only prised open again when doctors cut off her lashes.

Miss Griffin was warned she could have lost her sight forever and is still waiting to be told if there is any lasting damage.

The accident happened when she woke up and reached for a bottle of eyedrops in a bathroom cupboard.

But in her confused state she grabbed an identical-sized bottle of nail glue that was next to it.

Miss Griffin is worried about being seen as a dumb blonde, but she finds herself in the company of an Abbot of a Thai monastery - who further compounded his error by putting thinners in his eyes to try and rectify the problem. The earliest case of superglue-eyedrop confusion seems to have occurred in 1982. One publication (including management advice) describes finding 14 cases in 12 months at one emergency clinic.

Getting into the newspapers, if that rate of occurrence is typical, is a real achievement.

John Rentoul has been running an occasional series based on headlines to which the answer is “no”. These include:

He’s the outcast bishop who denies the Holocaust - yet has been welcomed back by the Pope. But are Bishop Williamson’s repugnant views the result of a festering grudge against Marks & Spencer?

No.

Is This Atlantis?

No.

And today’s

Is Gordon Brown Insane?

No.

John suggests that the accusation of madness when you are in disagreement with a politician is “a standard refuge of the over-expressive commentator”, but it’s far more common than that.

Over at Ouroboros, you'll find a look at what emerges from a very large comparative analysis of gene expression changes with aging. By finding the most important differences, and tracing back to the biological mechanisms associated with these genes, we should learn something about the validity of various theories of aging, and the importance of various potential strategies for slowing or reversing aging.

The core of the thing:

We performed a meta-analysis of age-related gene expression profiles using 27 datasets from mice, rats and humans. Our results reveal several common signatures of aging, including 56 genes consistently overexpressed with age, the most significant of which was APOD, and 17 genes underexpressed with age.

We characterized the biological processes associated with these signatures and found that age-related gene expression changes most notably involve an overexpression of inflammation and immune response genes and of genes associated with the lysosome. An underexpression of collagen genes and of genes associated with energy metabolism, particularly mitochondrial genes, as well as alterations in the expression of genes related to apoptosis, cell cycle and cellular senescence biomarkers, were also observed.

If you've been reading Fight Aging! for a while, you'll have seen most of these processes and systems mentioned in connection to the damage of aging. The failing immune system, the role of chronic inflammation, the biochemical junk cluttering the lysosome, mitochondrial DNA damage, senescent cells, and so forth.

As they point out at Ouroboros:

While this approach will likely fail to identify those genes that are age-regulated only in a single tissue, the advantage is that those genes that do come out of this analysis are likely to be the really interesting ones - components of a common aging program that operates in multiple tissues.

Centenarians get to be centenarians by surviving or not suffering the diseases that kill everyone else. So what kills centenarians? This isn't an academic question, as we'd like to engineer a future in which none of us suffer the major diseases of aging, and all of us make it past a century in good health. Understanding the processes that slay those who survive everything else the failing body can throw at us is just as essential to the future of longevity medicine as curing cancer and repairing mitochondria.

If forced to make an educated guess today, I'd have to say that the best evidence is for amyloidosis to be the killer of the oldest old - a buildup of metabolic byproducts that eventually clogs the body's systems to the point of failure. The Supercentenarian Research Foundation outlines some of the case for that conclusion:

Coles argues [that supercentenarians] aren't perishing from the typical scourges of old age, such as cancer, heart disease, stroke, and Alzheimer's Disease. What kills most of them, he says, is a condition, extremely rare among younger people, called senile cardiac TTR Amyloidosis. TTR is a protein that cradles the thyroid hormone thyroxine and whisks it around the body. In TTR Amyloidosis, the protein amasses in and clogs blood vessels, forcing the heart to work harder and eventually fail. "The same thing that happens in the pipes of an old house happens in your blood vessels," says Coles.

Folk from the Biogerontology Research Foundation (formed "to support the application of our knowledge of the mechanisms of ageing to the relief of disability, suffering and disease in old age") were kind enough to direct my attention today to a recent update from the amyloidosis research community:

Prof Pepys’s persistence pays off

Amyloidosis is caused by the build up of abnormal "amyloid" proteins in body tissues. Prof Pepys has long believed that the key to understanding the disease is a related blood protein called SAP, which sticks to amyloid fibres and stops enzymes removing them.

The FT has covered his work several times. My predecessor David Fishlock described in 1990 Prof Pepys’s discovery of a way to image SAP and amyloid fibres. I wrote in 1995 and 2002 about progress in developing a drug called CPHPC, which aimed to clear the destructive amyloid deposits from patients by removing the protective SAP from their blood.

Prof Pepys was working then in collaboration with Roche. But the Swiss pharmaceutical giant eventually pulled out.

"While we had promising early results [with CPHPC] they were not enough to benefit patients with advanced disease," he says. "Something more dramatic is needed."

That something turns out to a combination of CPHPC with an antibody - a molecular guidance system designed to seek out amyloid deposits in vital organs.

Now Prof Pepys has reached an agreement with another big pharmaceutical group, UK-based GlaxoSmithKline, to collaborate on producing a treatment for amyloidosis based on the CPHPC-antibody combination.

Those of us interested in progress towards the tools needed to remove or repair changes in our tissues that accumulate with age should follow amyloidosis research with interest. Some fraction of the degenerations of aging is caused by just this sort of buildup of unwanted chemical aggregates. Strategies under development for dealing with specific aggregates may turn out be more broadly applicable to future engineered longevity therapies.