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:
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.