Hormesis does not make sense except in the light of TOR-driven aging

Area of Science:

• Gerontology
• Molecular Biology
• Cellular Stress Response

Background:

• Hormesis, the concept that weak stresses extend lifespan, is controversial in gerontology.
• The prevailing view links aging to accumulated molecular damage, which contradicts hormesis if stresses cause damage.
• An alternative hypothesis suggests hormesis works by activating repair mechanisms to counteract damage.

Purpose of the Study:

• To resolve the paradox of hormesis and aging.
• To propose an alternative model for aging mechanisms.
• To categorize hormetic conditions based on their effects on aging pathways.

Main Methods:

• Challenging the molecular damage theory of aging.
• Proposing that aging is driven by overactivated signal-transduction pathways, particularly the TOR pathway.
• Classifying hormetic conditions into two groups: 'Hormesis A' (TOR inhibition) and 'Hormesis B' (increased aging tolerance).

Main Results:

• Aging is not primarily caused by molecular damage accumulation but by overactivated signaling pathways like TOR.
• 'Hormesis A' conditions (e.g., calorie restriction, rapamycin) inhibit the TOR pathway.
• 'Hormesis B' conditions (e.g., ischemic preconditioning) enhance the ability to survive aging-related complications.

Conclusions:

• Hormesis offers a new perspective on lifespan extension and aging.
• The TOR pathway is a key target for understanding and potentially modulating aging.
• Understanding the dual nature of hormesis (TOR inhibition vs. aging tolerance) is crucial for gerontological research.