Targeting ageing with rapamycin and its derivatives in humans: a systematic review

Area of Science:

• Gerontology and Pharmacology
• Molecular Biology and Aging Research

Background:

• The mechanistic target of rapamycin (mTOR) pathway is a key regulator of the aging process.
• Rapamycin and its analogs (rapalogs) are known inhibitors of mTOR.
• Understanding the impact of rapalogs on age-related physiological decline is crucial for developing interventions.

Approach:

• A systematic literature search was conducted across five databases.
• 18,400 unique articles were identified, and 19 studies met the inclusion criteria.
• The review synthesized data on the effects of rapamycin and rapalogs on aging-related physiological changes and diseases in adults.

Key Points:

• Rapalogs demonstrated improvements in immune, cardiovascular, and integumentary system parameters in healthy individuals and those with age-related diseases.
• No significant effects were observed on endocrine, muscular, or neurological systems.
• Adverse events in healthy individuals were minimal, but increased infections and adverse lipid profiles were noted in patients with age-related diseases.

Conclusions:

• Rapalogs show potential for mitigating specific age-related physiological changes, particularly in the immune, cardiovascular, and integumentary systems.
• Further research is needed to explore effects on unexamined systems (respiratory, digestive, renal, reproductive) and long-term outcomes.
• Careful consideration of potential adverse effects, such as infections and lipid changes, is warranted in patient populations.