Rapamycin: Does it Actually Help You Live Longer?

Rapamycin: Does it Actually Help You Live Longer?

Today's most discussed longevity and anti-aging medication is Rapamycin. Surprisingly, Rapamycin was discovered in soil bacteria from Easter Island and was originally used as an antibiotic and antifungal. has become a compelling focus of longevity research. More recently, it was discovered to inhibits a key aging protein called mTOR (mechanistic target of rapamycin). But does Rapamycin actually help you live longer and healthier?

Rapamycin and Life Limiting Diseases

Living longer means reducing the risks of diseases that will ultimately lead to our death. The 4 key diseases we'll discuss are:

• Cancer
• Cardiovascular disease (the most common cause of death)
• Neurogenerative disease
• Sarcopenia (loss of muscle mass, which is highly correlated with premature death)

Additionally, Rapamycin also reduces early senescence, or cell death, of stem cells.

Rapamycin and Cancer

Cancer incidence increases significantly with age, making it critical in longevity medicine protocols. Rapamycin has shown promise in extending lifespan partly through its cancer-suppressive properties. This is believed to be through MTOR-inhibition causing an arrest of cell growth and an increase in cell death. Rapamycin also reduces the rate of new blood vessel growth, which facilitates metastases. In the setting of cancer, this "slow down" of cellular proliferation is desired.

In fact, the following cancers are likely suppressed by Rapamycin:

• Skin cancer
• Kaposi's sarcoma
• Kidney cancer metastases (provoked in mice)

Cardiovascular Disease and Rapamycin

Cardiovascular diseases (CVD) is the most common life-limiting disease and is closely linked to the aging process. Emerging data supports Rapamycin's beneficial effects with inflammation, calcium regulation, mitochondrial metabolism, and cardiac hypertrophy - all of which are negatively impacted with aging. These effects appear to result from its inhibition of mTORC1, thereby decreasing inflammation and oxidative stress - two central contributors to cardiovascular aging.

In addition to increasing mammalian lifespan, MTORC-1 inhibition facilatates the following cardioprotective benefits:

1. Reduce harmful overgrowth of heart muscle that could lead to heart failure
2. Minimize heart muscle damage after heart attacks
3. Lessen impact of heart problems from metabolic disorders

While studies are typically done in mammals, such as this fascinating study showing less heart cell death after heart attack, there studies ongoing in humans.

Rapamycin for Neurodegenerative Disease

Neurodegenerative diseases such as Alzheimer's and Parkinson’s also increase markedly with age.

Alzheimer's Disease and MTOR Hyperactivation

mTOR activity (which is suppressed by Rapamycin) appears hyperactivated in Alzheimer's with many consequences:

• Increased deposition and reduced clearance of amyloid-beta (Aβ) oligomers
• Suppressed autophagy, thereby reducing clearance of toxic proteins like Aβ and hyperphosphorylated tau
• Exacerbated tau pathology by promoting hyperphosphorylation and aggregation through mTOR-driven kinases
• Increased neuronal insulin resistance, possibly contributing further to impaired neuronal function and cognitive deficits

Rapamycin, by inhibiting mTOR may reverse these:

• Restore autophagic processes
• Enhance the clearance of Aβ and tau aggregates
• Improve insulin signaling, and potentially rescues synaptic function and cognitive performance

Parkinson's Disease and Rapamycin

Like in Alzheimer's, Parkinson's disease also appears to alter mTOR signaling. Oxidative stress appears to be a key driver in Parkinson's disease, likely from mitochondrial dysfunction and reduced electron transport Complex I activity. This oxidative damage appears to alter the mTOR/Akt signaling pathway, leading to dopaminergic neuron loss (the main type of neuron loss in Parkinson's).

Rapamycin appears to rebalance mTOR hyperactivation in Parkinson's, similar to in Alzheimer's models:

• Enhances autophagic clearance of harmful protein aggregates like α-synuclein
• Restores insulin resistance
• May promote neuronal survival pathways (through Akt phosphorylation)
• Protects neurons from reactive oxygen species (ROS) damage

Sarcopenia and Rapamycin

Rapamycin may help extend longevity by protecting against sarcopenia, the age-related loss of muscle mass and strength. This is crucial for longevity because sarcopenia increases the risk of fractures, which may be life-limiting in the elderly. Normally, chronic activation of the cellular growth pathway mTORC1 leads to muscle damage through oxidative stress, mitochondrial dysfunction, and impaired autophagy, ultimately causing muscle atrophy and fiber loss. Rapamycin, as an mTORC1 inhibitor, prevents these harmful effects, preserving muscle integrity during aging. Experimental evidence from mice and rats demonstrates that rapamycin treatment significantly reduces muscle fiber loss, maintains muscle size, and enhances survival, suggesting that carefully optimized rapamycin protocols could be beneficial against age-related muscle deterioration and frailty

Balancing Potential Benefits and Risks of Rapamycin

Despite promising results in early clinical studies, Rapamycin is not without risks. Long-term mTOR inhibition could lead to side effects, including impaired wound healing, mouth sores, potential immunosuppression, metabolic disturbances, and other complications. Medical supervision is very important, and your longevity doctor should monitor your labs throughout treatment and tailor your protocol based on your individual health assessment. Speak with an expert at Clarus Health today to learn if Rapamycin may be helpful for your longevity goals.