Research Perspective Volume 13, Issue 3 pp 3167—3175

DNA- and telomere-damage does not limit lifespan: evidence from rapamycin

Rapamycin extends lifespan in natural but not progeroid mice. (A) Natural mice. Hyperfunctional aging (green/yellow/red arrow) progresses from development (green) to diseases (red), reaching death threshold and limiting lifespan. Accumulation of molecular damage (gray arrow) is slow and does not reach death threshold in animal lifetime. It would take longer to die from molecular damage. Treatment with rapamycin (RAPA) extends lifespan by slowing down mTOR-driven aging (B) Progeroid, telomerase- or DNA-repair-deficient mice. Accumulation of molecular damage (gray arrow) is artificially accelerated to become life-limiting. Treatment with rapamycin (RAPA) cannot extend lifespan.

Figure 1. Rapamycin extends lifespan in natural but not progeroid mice. (A) Natural mice. Hyperfunctional aging (green/yellow/red arrow) progresses from development (green) to diseases (red), reaching death threshold and limiting lifespan. Accumulation of molecular damage (gray arrow) is slow and does not reach death threshold in animal lifetime. It would take longer to die from molecular damage. Treatment with rapamycin (RAPA) extends lifespan by slowing down mTOR-driven aging (B) Progeroid, telomerase- or DNA-repair-deficient mice. Accumulation of molecular damage (gray arrow) is artificially accelerated to become life-limiting. Treatment with rapamycin (RAPA) cannot extend lifespan.