Are there human studies on the use of Sirolimus (Rapamycin) for senescence?

From the Guidelines

Yes, there are human studies on the use of Sirolimus (Rapamycin) for senescence, with evidence suggesting its potential to improve adaptive immune function and reduce markers of senescence in peripheral blood mononuclear cells (PBMCs) 1.

Key Findings

• A study published in Cell in 2024 found that short-term treatment with rapamycin can improve adaptive immune function and reduce markers of senescence and SASP in PBMCs 1.
• The study also noted that an assay based on analysis of CDKN2A mRNA in PBMCs or selected subsets such as CD3+ T cells can be used to detect the senescence-like state in immune cell populations 1.
• Another study published in Nature Reviews Nephrology in 2024 found that sirolimus (also known as rapamycin) may be an alternative to everolimus for mTORC1 inhibition in TSC, with similar dosing strategies and efficacy 1.

Dosage and Administration

• The optimal dosage of rapamycin for senescence is not established, but studies have used dosages ranging from 1mg daily to 5-10mg once weekly 1.
• Intermittent dosing regimens may provide potential benefits while minimizing side effects, but more research is needed to determine the best dosing strategy 1.

Mechanism of Action

• The mechanism behind rapamycin's potential anti-aging effects involves inhibition of mTOR (mechanistic target of rapamycin), a cellular pathway that regulates growth, metabolism, and cellular aging 1.

Side Effects and Safety

• Common side effects of rapamycin include mouth sores, elevated blood lipids, and potential immunosuppression at higher doses 1.
• Careful monitoring and individualized dosing are necessary to minimize side effects and ensure safe use 1.

From the Research

Human Studies on Sirolimus (Rapamycin) for Senescence

• There are human studies on the use of Sirolimus (Rapamycin) for senescence, with a focus on its potential as an anti-aging therapeutic 2.
• A clinical trial found that topical rapamycin reduced markers of senescence and aging in human skin, with significant reductions in p16INK4A protein levels and increases in collagen VII protein levels 2.
• The study suggests that rapamycin treatment may be a potential anti-aging therapy with efficacy in humans, with improvements in clinical appearance of the skin and histological markers of aging 2.
• Other studies have discussed the potential of rapamycin as a geroprotector, with ongoing or upcoming clinical trials aiming to address outstanding questions regarding its safety, pharmacokinetics, pharmacodynamics, and efficacy in humans 3, 4, 5.
• The specificity of rapamycin as an mTOR inhibitor has also been evaluated, with results indicating a striking specificity towards mTOR 6.

Key Findings

• Topical rapamycin has been shown to reduce senescence and markers of aging in human skin 2.
• Rapamycin has been found to have a high specificity towards mTOR, with minimal effects on other cellular processes 6.
• Clinical trials are ongoing or upcoming to investigate the safety and efficacy of rapamycin as an anti-aging therapeutic in humans 3, 4, 5.

Study Limitations

• The current evidence for rapamycin in lifespan extension and organ aging is fragmented and scattered 4.
• Concerns over the risk of potentially serious side effects in humans, including immunosuppression and metabolic disruptions, have limited the translation of rapamycin as a treatment for aging-associated conditions 3, 5.