How Are Aging Signals Dysfunctional?

The chronic conditions associated with aging are caused by and feed unhealthy aging pathways. But what creates the environment for unhealthy aging? Experts in anti-aging research have identified some of the key factors that promote an unhealthy cellular environment, including: ^{(iii.80, 82)}

• Obesity
• Toxins
• Genetics

mTOR and AMPK

At the cellular level, the mTOR signaling pathway is thought to be a central factor in aging. It's promoted by obesity and overeating. ^(iii.70)

For example, obesity and chronic inflammation causes high insulin and blood sugar levels. These activate the mTOR nutrient pathway, which reduces insulin receptors in cells. Loss of insulin receptors which can lead to insulin resistance and type 2 diabetes. Calorie restriction and drugs that mimic its effects (CRMs such as metformin and rapamycin) all target and block the activation of mTOR. ^(iii.70)

AMPK is a kinase protein involved in metabolism of fats and carbohydrates. CRMs also target AMPK. But unlike how they block mTOR, CRMs activate AMPK. In people with the chronic conditions associated with metabolic syndrome, AMPK is beneficial. Metabolic syndrome diseases are also conditions associated with aging (e.g., heart disease and type-2 diabetes). Increasing AMPK in muscle cells reduces inflammation, insulin resistance, and triglyceride cholesterol levels. ^(iii.83)

Unhealthy Signal Pathways

The unhealthy signal pathways that lead to chronic diseases associated with aging include: ^{(iii.8, 62, 72-73, 75, 79, 81)}

Figure III.4: Pathways to Unhealthy Aging

These signaling pathways (e.g., mTOR activation, chronic inflammation, and free radical damage) also accelerate or promote cell functions that naturally occur as cells age. These include: ^{(iii.73, 81)}

• Shortening the ends of DNA strands (called telomeres) that protect against DNA errors when cells replicate.
• Decreasing the number of adult stem cells that have the ability to regenerate themselves.

Targeting mTOR

Studies show that blocking the mTOR nutrient signaling pathway helps prevent unhealthy aging. ^(iii.70)