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May 25, 2012

Treating Amyloidosis could extend maximum human lifespan

Extreme Longevity - Supercentenarians and transthyretin amyloidosis: The next frontier of human life extension (Preventitive Medicine Journal, 3 pages)

Supercentenarians are persons who have lived beyond the age of 110. Currently there are only about 80 such known individuals in the world whose age is verified.

In a newly published review Drs. Stephen Coles and Thomas Young of the UCLA Gerontology Research Group point out what it may be that is killing supercentenarians: amyloidosis.

Amyloidosis is a disease state hallmarked by the deposition of fibers of abnormally clumped masses of transthyretin. The protein transthyretin normally acts to carry thyroid and other hormones. Mutations in the gene make the fibers abnormally sticky and they tend to clump into long fibers which are deposited in multiple organs.

Through early onset amyloidosis leads to disease, it is of interests that supercentanarians all seem to have significant amounts of it. Though not proven it is possible the amyloid is killing them.

These persons have already escaped the typical causes of death however they have lived for so long, the normally innocuous amounts of amyloid that increase with age may actually become toxic to them because they have lived so many years.

Where this line of reasoning gets exciting is that experimental drugs exists which may eliminate amyloid.

These drugs are being studied for young persons with pathological amyloidosis. If they work, what would happen if they were adminstered to persons over age 95? Perhaps it is possible they could become the first drugs to extend human lifespan beyond current theoretical limits.

Is amyloidosis a part of the aging process, or is it merely one more chronic disease that can be treated? Will treating amyloidosis lead to increases in human lifespan? Both first-generation and second-generation drugs, such as Diltiazem, Verapamil, Celastrol, 4-PDA, taurine-conjugated ursodeoxycholic acid, and CHPHC, are under development for the management of the disease (Coelho et
al., 2008; Balch et al., 2008). It seems to us that these questions may lead us to the next frontier in the extension of human lifespan. At the very least, the recognition that amyloidosis is a common and treatable condition in the oldest old should lead supercentenarians to having a better quality of life in the future, a further confirmation of what has been called the “Compression of Morbidity”





Amyloidosis is defined as “a disorder in which insoluble protein fibers systematically infiltrate multiple tissues and organs, progressively impairing their function.” It occurs when native or mutant polypeptides misfold and aggregate as fibrils. Amyloidosis can take several forms: primary (or idiopathic) amyloidosis is seen as localized to certain organs (such as the liver or the heart) and not associated with other diseases except for multiple myeloma, while secondary amyloidosis is linked to chronic disease. In addition, as stated earlier, some types of amyloidosis are found to be hereditary. Essentially, amyloidosis causes death through a clogging of blood vessels: just as a drain pipe in an old house eventually becomes blocked, impeding the flow of water. So the buildup of long chains of extra-cellular amyloid proteins eventually choke off the function of vital organs (such as the heart and liver), ultimately leading to death. Just as plaque build-up in coronary arteries can lead to Myocardial Infarction (an MI), so the buildup of sticky amyloid fibers (or ‘lardaceous’ tissue) leads to the failure of the affected organs. Physicians have distinguished at least 27 different types of proteins associated with amyloid formation. The most commonlyknown
type, beta amyloid (Aβ or A-beta) is a polypeptide of amino acids which appears as the primary constituent of plaques in the brains of patients with Alzheimer's disease. Other common
types include fibrils derived from monoclonal immunoglobulin light chains (such as kappa or lambda) caused by Multiple Myeloma (a cancer of the plasma cells in the blood), which can be distinguished by immunohistochemical staining following Congo-Red staining.

Ironically, it is only after the gains made in other fields have slowed that the patients now demand that the problem of amyloidosis no longer be ignored; with longevity gains made in other aspects of human aging (such as atherosclerosis and hypertension), the law of diminishing returns suggests that more improvements can be made in areas largely unexplored or untreated. Certainly, amyloidosis, long an apparent but overlooked cause of death in extreme old age (and in a few younger individuals with a genetic propensity for amyloid buildup) is now a major problem on the frontier of extending human lifespan. For those who have claimed that ‘eliminating cancer and heart disease would only add about ten years to the human lifespan’ because people would die of something else, it seems increasingly likely that the ‘something else’ could well be amyloidosis.

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