Yet another confirmation that cortisol, while being life-saving in acute stress situations, can shorten lifespan if chronically elevated. In fact, according to the study below, antagonizing the effects of even normal cortisol levels may extend lifespan. This corroborates Ray’s statement that all the symptoms of aging (and thus every chronic disease) can be reliably reproduced in even youthful organisms by the administration of sufficiently high doses of cortisol. An interesting finding of the study was that the anti-aging effects was due to improved mitochondrial function, so this suggests (again) that any benefit or risk from a specific substance is likely ultimately due to its effects on metabolism/mitochondria. And it just so happens that cortisol does suppress mitochondrial function, while simultaneously enhancing both fatty acid synthesis and fatty acid oxidation, as well as lipolysis. Finally, the study compared the effects of cortisol blocking to the effects of the well-known life-extension drug rapamycin, which works by blocking the mTOR protein. In fact, blocking cortisol extended lifespan by 40%+ more, compared to rapamycin and without the known (and very dangerous) side effects of rapamycin (immunosuppression). The two drugs were not synergistic when used together, suggesting they work through the same pathway.
The anti-cortisol drug the study used was the well-known Mifepristone/RU486. However, there is plenty of evidence that progesterone, DHEA, testosterone, DHT, etc are also capable of antagonizing the effects of cortisol. As a curious example, I would point to both Elon Musk and (especially) Jeff Bezos, who are some of the most well-known users of testosterone (TRT). Both have had doctors and the general public commenting that since starting TRT they have able to “age in reverse” and that is readily visible by comparing pictures from their younger years (20s and 30s) to recent ones. While medicine will probably attribute those beneficial effects on testosterone (T) being an “anabolic” steroid, in reality most of the “anabolism” stems from the anti-catabolic effects of T (it is a cortisol blocker at the receptor level, just like RU486). As such, OTC alternatives with known anti-cortisol effects such as progesterone/DHEA or pregnenolone may also be able to achieve the same effect.
https://doi.org/10.1080/19336934.2024.2419151
“…The University of Southern California scientists directly compared the effects of mifepristone on female fruit flies with another drug that has shown anti-aging potential, the immunosuppressant rapamycin. They found that both drugs taken separately improved the flies’ longevity, though mifepristone performed a bit better, extending the flies’ lifespan by a median 114% compared to 81% for rapamycin. However, when both drugs were used together on the flies, the flies actually went on to have a slightly lower lifespan than normal—indicating that the drugs work in a very similar way to boost longevity, the researchers said. The team’s other experiments suggest that both drugs do this by improving the cells’ ability to clean up their damaged or dysfunctional mitochondria…”
