Chronic mechanistic target of rapamycin inhibition: preventing cancer to delay aging, or vice versa?

Area of Science:

• Gerontology
• Oncology
• Pharmacology

Background:

• Aging and cancer are closely linked, with limited strategies to address both concurrently.
• Diet and growth factor restriction show promise in preclinical models for mitigating aging and cancer.
• The mechanistic target of rapamycin (mTOR) pathway is implicated in both aging and cancer processes.

Purpose of the Study:

• To investigate the potential of enteric rapamycin (eRapa) as a combined therapeutic approach for aging and cancer.
• To review the role of mTOR in cancer and aging and the clinical status of mTOR inhibitors.
• To address misconceptions regarding rapamycin's immunosuppressive effects.

Main Methods:

• Chronic administration of an enteric formulation of rapamycin (eRapa) to genetically heterogeneous mice.
• Evaluation of lifespan extension and cancer amelioration in treated mice.
• Review of existing literature on mTOR, cancer, aging, and immune surveillance.

Main Results:

• Chronic eRapa treatment significantly extended maximum lifespan in both male and female mice, regardless of treatment initiation timing (mid or late life).
• eRapa demonstrated cancer amelioration effects in treated mice.
• Findings suggest eRapa's potential as a pharmacological intervention for age-related diseases, including cancer.

Conclusions:

• eRapa represents a promising pharmacological strategy for simultaneously addressing cancer and aging.
• Further research is needed to understand mTOR inhibitor responses within the tumor immune surveillance system.
• Development of comprehensive, safe cancer prevention strategies that also mitigate aging effects is crucial, especially for the aging population.