There’s multiple FDA approved drugs available today to prevent an age-related disease that most supercentenarians (110+) succumb to, approx 70%, and that’s misfolded protein accumulation of transthyretin (TTR), called wild-type TTR amyloidosis or ATTR. The rates of ATTR accumulation in elderly seems to be around 25% for 80+.
It’s a protein that transports thyroid hormones and retinol. Every protein sequence is folded into its structure which creates its physical function in the body, for some reason with aging TTR protein can be misfolded, and thus not function and get stuck in the body. In organs like the heart, kidney, etc, and cause conditions like heart failure, and increase total death.
The rates of the wild-type ATTR on autopsy in elderly at ~25%, and 70% death of supercentenarians, along with what appears to be relatively safe preventative treatment that decreases misfolding is the most bullish case for me. The accumulation seems to cause multiple diseases as well.
Prevalence:
25%, 85+ (Tanskanen, 2008).
25%, 75+ (Porcari, 2021).
From a study from 2012, let me know if you find any more recent papers or looking at cause of death of supercentenarians:
Emerging SRF autopsy data continue to strongly suggest that supercentenarians die of amyloidosis-related causes (the primary cause of death in ~70% with the balance due to aspiration pneumonia). It is still too early to draw definitive conclusions; however, these early results suggest that we need to take a second look at implicating amyloidosis as one of the major components of the aging process. As stated above, 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. …
For prevention, just looking quickly at the trial for tafamidis in NEJM it looks safe, I’m not taking it yet, going to have to research this more, but preventing most cases of ASCVD with early apoB reduction, and other therapies, this becomes more lucrative:
The overall incidence and type of adverse events were similar in the tafamidis and placebo groups. Discontinuation of the trial drug owing to adverse events that occurred during treatment was less common in patients who received tafamidis than in those who received placebo, and dose reductions were uncommon and occurred more often in the placebo group.
https://www.nejm.org/doi/full/10.1056/NEJMoa1805689
https://x.com/KarlPfleger/status/1889001506512490500#m
Please post any studies relating to ATTR or amylodosis here.
