Tag Archives: Rapamycin

Rapamycin May Extend Lifespan by Safeguarding Against DNA Damage

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Illustration of rapamycin (red), a drug that inhibits proteins known as MTOR (blue)

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The anti-aging benefits of rapamycin may be related, at least in part, to its ability to prevent DNA damage in immune cells.

Initially created as an immunosuppressant for organ transplant patients, rapamycin blocks the function of the MTOR protein, which is crucial for cell growth and division. Studies suggest that low doses can extend the lifespan of various organisms, including the mouse, potentially by disrupting processes associated with aging, such as inflammation, intracellular breakdown, and decline in mitochondrial function.

Recent research by Lynn Cox and colleagues at Oxford University has demonstrated that rapamycin also appears to prevent DNA damage in certain types of immune cells. DNA damage is one of the key factors contributing to aging in our immune system, accelerating the aging process throughout the body.

The researchers conducted experiments with human T cells, a type of white blood cell responsible for fighting infections. When T cells were exposed to an antibiotic named zeocin alongside rapamycin, significant DNA damage occurred.

Results showed that rapamycin lowered DNA damage and tripled cell survival rates compared to T cells exposed to zeocin alone.

The researchers found no indication that the observed effects were due to other actions of rapamycin, such as preventing cell failure. “We consistently observe this effect regardless of whether rapamycin is administered prior to, during, or post-injury,” noted team member Ghada Arsare at Oxford University.

The rapid response suggests a direct impact. “The effect is very swift, indicating it influences the DNA damage response and accumulation. The lesions observed last about four hours, so it’s unlikely that there are downstream effects impacting other processes,” explained Cox.

According to Matt Kaeberlein from Washington University in Seattle, the findings support the notion that rapamycin can directly protect DNA, but “this is not the critical mechanism.” Researchers aim to explore rapamycin-induced alterations in RNA and proteins produced in immune cells.

In a separate part of the study, nine men aged 50 to 80 were assigned to receive either 1 milligram of rapamycin or a placebo daily. Blood tests conducted eight weeks later revealed that T cells from men taking rapamycin exhibited less DNA damage. Furthermore, neither group experienced a decrease in overall white blood cell counts, indicating that rapamycin does not negatively impact immune functionality. “Our findings confirm that low doses are safe, which is crucial,” stated Cox.

Mitigating DNA damage in the immune system may provide a pathway for reducing overall aging, according to Cox. Arsare highlighted the potential for rapamycin to be used preventively, such as for astronauts exposed to cosmic radiation.

“Rapamycin is particularly promising in addressing aging-related issues where DNA damage is a significant factor, such as skin aging,” noted Kaeberlein. Referring to a study, he added that local use of rapamycin reduces aging markers in human skin. However, he cautioned against generalizing results to other types of damage, such as radiation, given that Cox’s team used antibiotics to create DNA damage.

Zahida Sultanova from the University of East Anglia emphasized the necessity for trials involving women and individuals across various age groups, as the placebo-controlled experiments were limited to older men. Evidence from non-human animal studies indicates that rapamycin may have sex-specific and age-specific effects.

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Source: www.newscientist.com

Rapamycin May Boost Lifespan More Significantly with Reduced Caloric Intake

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An illustration depicting the drug rapamycin (red) inhibiting the protein complex MTORC1, influencing cell functionality

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The drug rapamycin shows effects on life extension that are nearly comparable to calorie restriction, based on the largest study exploring the lifespan of various vertebrate species.

Researchers are probing if lifestyle changes like diet and exercise can enhance longevity while mitigating aging-related health issues. For instance, calorie restriction, when balanced with nutritional needs, has demonstrated extensions of lifespan in non-human animals of up to 40%.

“In our field, we have long recognized that calorie restriction often yields positive results,” says Matt Kaeberlein, who was not involved in the recent research from Washington University in Seattle.

Another area of interest lies with potential anti-aging medications, such as rapamycin, initially developed as an immunosuppressant. The combination of rapamycin with the cancer treatment trametinib has shown a 30% increase in mouse lifespan earlier this year.

Currently, Zahida Sultanova from the University of East Anglia, along with her collaborators, is reviewing data from 167 studies on lifespan interventions across eight vertebrate species, such as fish, mice, rats, and rhesus monkeys, though not in humans.

The findings indicated that dietary restrictions, regardless of whether they primarily involve calorie reduction or intermittent fasting, extend the lifespan of all eight species, regardless of sex. Rapamycin appears to produce effects similar to these. They also examined the type 2 diabetes medication metformin, which has been suggested as a potential longevity stimulant, but found no benefits regarding lifespan.

However, Sultanova advises against individuals self-prescribing rapamycin based on these findings. “High doses of rapamycin can have side effects, as it is designed to suppress the immune system,” she states, noting that studies in mice have indicated it might affect reproduction. Nonetheless, early data from a recent trial suggest low-dose rapamycin is relatively safe for healthy elderly individuals.

Kaeberlein also warns against using medication or limiting calories solely to combat aging, as this could be linked to physical debilitation and mental health issues. “We must better understand the ratio of risks to rewards in humans before making such decisions,” he states. “Rapamycin might be beneficial for certain individuals, and ongoing research aims to clarify who those individuals are.”

Other medications similar to rapamycin, termed Rapalogs, might offer even more promising options with fewer adverse effects for lifespan extension, claims Sultanova.

Kaeberlein adds that while these results align with existing literature, “the effect sizes observed in shorter lifespans typically surpass those in longer ones, so caution is warranted when comparing across species.”

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Source: www.newscientist.com

Rapamycin could potentially enhance the safety of epilepsy medications in pregnant women

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Sodium valproate is an effective drug for epilepsy, but its consumption is not recommended during pregnancy

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The drug rapamycin may prevent the epilepsy drug sodium valproate from causing developmental problems during pregnancy.

Sodium valproate is used to treat epilepsy, bipolar disorder, and sometimes migraines. Although effective, it is not recommended during pregnancy as it can cause birth defects such as spina bifida and lifelong learning disabilities.

Giovanni Pietrogrande Researchers from the University of Queensland in Australia wanted to understand why sodium valproate could have such an effect. So they used stem cells to create mini-spinal cords called organoids in the lab. These mimic the spine of a fetus during early pregnancy.

When organoids were exposed to sodium valproate, their cells changed in ways that may be associated with risk of congenital disease.

The researchers looked for reasons for this and found that activity in one of the cell's signaling pathways, called mTOR, indicates that cells are aging. This is a process in which cells stop growing but do not die, but instead continue to release chemicals that can cause inflammation.

Rapamycin, which was initially developed as an immunosuppressant but has some promise for anti-aging effects, also targets the mTOR pathway.

In another experiment, researchers exposed a new set of spinal cord organoids to a combination of sodium valproate and rapamycin and found that no aging occurred. They then replicated this test in zebrafish larvae and found that the cells similarly did not undergo senescence and showed no signs of the changes that occur when exposed to sodium valproate alone.

Rather than doctors discontinuing sodium valproate if an epileptic patient is pregnant or may become pregnant, someday doctors may be able to prevent the negative effects of sodium valproate by combining it with rapamycin. Pietro Grande says. Human studies are needed to make this recommendation.

Frank Vajda The University of Melbourne says sodium valproate is “a critically important drug and the single most effective treatment for generalized seizures, where abnormal electrical activity begins in both halves of the brain at the same time.”

“I think this is a very important paper that could lead to a return to the level of importance that this drug had before its side effects were discovered,” he says.

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Source: www.newscientist.com