Is it Possible to Reverse Alzheimer's Disease?
Rapamycin, Ageing and the lies David Sinclair told us
Neuro Athletes,
If you like the idea of living as long as possible, rapamycin may be the drug for you. Originally developed as an immunosuppressant for organ transplant patients, it has found a new lease on life as a potential anti-ageing drug and as a treatment for Dementia.
On this note, how annoying is it when scientists make huge bold claims, marketing companies go out and market a product then to have another scientist disprove the paper and theory of that claim? How many times do we have to put up with this?
Frankly, I am tired of it…
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mTOR
Aging, a process none of us can escape, is characterized by the ‘gradual deterioration of functional characteristics’. Aging affects all parts of our bodies, including our microbiome. It is, in other words, very complicated.
mTOR is a protein kinase (an enzyme that modifies other proteins) that regulates cell growth and metabolism. It’s a complex pathway that’s critical to many cellular processes. But, in short, it’s a survival mechanism that signals to the body and cells that they should grow during times of plenty and not grow when food is scarce. It’s a bit like the central processing unit of a computer that makes all the complex decisions relating to cellular growth and it’s one of the longevity pathways.
Too much mTOR has been linked to a shortened lifespan, cancers, and many chronic health conditions, and too little mTOR could cause other health issues such as liver problems, muscle atrophy, delayed healing, and disrupted insulin sensitivity. That should confuse you and make you a bit frustrated right? I often wonder why many things in biology are like Goldielocks - too little is bad and too much is bad.
Primer on Rapamycin
The compound rapamycin is proposed as a major life extension approach, but what do we really know? Rapamycin was isolated in 1972 from a bacterium found on Easter Island, aka Rapa Nui – hence the name. Rapamycin is thought to exert its life-extending properties by mimicking the effect of caloric restriction, one of the most reliable ways to extend lifespan in non-human animals. It targets a signalling molecule called mTOR (an acronym for mechanistic target of rapamycin) which is an important node in our nutrient-sensing pathways.
Lack of food switches mTOR off and activates emergency systems that enable us to survive periods of starvation.
These pathways include autophagy, the process by which cells scavenge dysfunctional organelles and molecules for energy. This reduces the accumulation of the detritus that normally clog up our tissues as we get older, and hence slows or even reverses the ageing process.
Doing a clinical trial of rapamycin in humans is considered almost impossible – it would take decades to detect any longevity effects. But a trial has just begun in pet dogs, which suffer similar age-related decline as humans but live much shorter lives.
Rapamycin and Alzheimer’s Disease: a double-edged sword?
Numerous studies have reported that inhibition of MTOR (mechanistic target of rapamycin kinase) clearly reduces Alzheimer disease neuropathological hallmarks in mouse models. This has resulted in calls for the use of the MTOR inhibitor rapamycin for the treatment of dementia in humans.
Unfortunately, intervention with rapamycin in these mouse studies commenced before or early in the appearance of these pathological hallmarks. Later in Alzheimer disease, when dementia actually manifests, the brain's lysosomal system is severely damaged and treatment with rapamycin is likely to exacerbate this damage.
The Truth about Resveratrol
Resveratrol — an antioxidant found in foods and drinks such as red wine, chocolate and grapes — has been purported to have anti-aging effects, but a new study suggests the compound may not help people live longer after all.
In the study of about 800 older adults in Italy, people who ate a resveratrol-rich diet were just as likely to die over a nine-year period, compared with those who consumed small amounts of the compound.
In addition, consuming high amounts of resveratrol was not linked with a reduced risk of heart disease or cancer.
In my latest episode of The Neuro Experience Podcast, Dr Matt Kaeberlein, PhD said that David Sinclair’s paper on Resveratrol increasing lifespan was disproved.
The bottom line on resveratrol
To take the most evidence-based approach, it is important to acknowledge that more research is needed to determine how or when resveratrol activates sirtuins, whether or not this activation occurs in humans and the exact impact of this to human health. It is also important to acknowledge that research takes years. More research is needed.
We know that resveratrol has been shown to extend lifespan among an array of organism and animal models and also shown to provide benefits to humans through numerous human RCT’s, especially with normal and safe dosages. Activation of SIRT1 is still a potential mechanism for resveratrol’s health benefits. However, it is not the only one.
Much of the controversy has resulted from individuals cherry-picking studies which have not had favorable results, although credible science requires a more holistic overview of the research to reach a conclusion: looking into systematic reviews and meta-analysis regarding the compound is important to the story. With that in mind, results from systematic reviews and meta-analysis’, such as the one mentioned above, have a much less controversial take on resveratrol.
When making a decision to take a supplement, always reach out to your doctor, read through research and weigh in the pros and cons.
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