Rapamycin: From Organ Transplantation To Anti-Aging Agent?
Rapamycin, a drug that has been used for decades to prevent organ transplant rejection and treat rare diseases, has gained much attention in recent years as a possible anti-aging agent.
It is a natural compound discovered in 1972 from a soil bacterium found on Easter Island, also known as Rapa Nui. The name rapamycin comes from the native name of the island. It belongs to a class of drugs called macrolides, which have antibiotic, antifungal, and immunosuppressive properties.
But how exactly does it work?
Rapamycin works by inhibiting a protein called mTOR (mechanistic or mammalian target of rapamycin), which is involved in many cellular processes, such as growth, metabolism, survival, and aging. mTOR acts as a sensor of nutrient availability and environmental stress and regulates the balance between anabolic and catabolic activities in the cell.
When mTOR is activated, it promotes cell growth and proliferation but also increases oxidative stress and cellular damage. When it is inhibited, it triggers a state of cellular stress resistance, which enhances autophagy, DNA repair, antioxidant defense, and stem cell function.
How can it help?
Several studies have shown that rapamycin can extend lifespan and delay age-related diseases in different animal models. For example, rapamycin increased the median lifespan of mice by 9% to 14% when given in late adulthood. It also improved cardiac function, cognitive performance, immune response, bone density, and muscle strength in aged mice.
Rapamycin may also have beneficial effects on human aging. It has been used to treat patients with a rare genetic disorder called Hutchinson-Gilford progeria syndrome (HGPS), which causes accelerated aging and premature death. Rapamycin improved some of the clinical features of HGPS, such as skin abnormalities, hair loss, joint stiffness, and vascular calcification.
Cancer, diabetes, obesity, neurodegeneration, and cardiovascular disease are all linked to aging in humans, and rapamycin has the potential to treat or prevent these conditions. It has anti-tumor properties by inhibiting cancer cell growth and angiogenesis (the formation of new blood vessels). It also improves insulin sensitivity, glucose metabolism, lipid profile, and inflammation by modulating mTOR signaling in various tissues.
What about side effects?
Despite its promising potential as an anti-aging drug, rapamycin has some drawbacks and limitations. It has several side effects when used as an immunosuppressant for organ transplant patients, such as the increased risk of infections, diabetes, hyperlipidemia (high blood fat levels), mouth ulcers, skin rashes, edema (swelling), anemia (low red blood cell count), and impaired wound healing.
Some aspects of aging unrelated to mTOR signaling may also be negatively affected by rapamycin. For instance, it may impair mitochondrial function and biogenesis (the formation of new mitochondria), which are essential for cellular energy production and oxidative stress resistance. Rapamycin may also interfere with hormonal balance and reproductive function by affecting the hypothalamic-pituitary-gonadal axis.
Finding the best time and dose to administer rapamycin is another difficulty when treating aging:
● It has complex pharmacokinetics (how the drug moves within the body) and pharmacodynamics (how the drug affects the body).
● It has a low bioavailability (how much of the drug reaches the bloodstream) when taken orally and varies depending on food intake and individual factors.
● It also has a long half-life (how long it takes for half of the drug to be eliminated from the body) of about 60 hours in humans.
To sum up, preliminary animal studies display that rapamycin could be a promising option for improving health span and extending lifespan by copying the effects of calorie restriction and activating cellular stress resistance mechanisms. It has shown benefits in various animal models and has also been used to treat a rare genetic disorder that causes early aging in humans. However, there are also drawbacks and limitations that leave something wanting, such as impaired mitochondrial function and hormonal balance and the best dose and timing of administration. More research is needed to find out the long-term safety and effectiveness of rapamycin in humans. To this date, cyclic administration (6 weeks on and 6 weeks off) provides more energy, quicker recovery time, increased hair growth and improved skin resilience in several clients currently on the program.
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