“If we completely cured cancer, average lifespan would only increase by 2.8 years. That’s why we need explicit anti-aging research.” @elidourado

How do we solve aging given what we know?

To solve aging we need to inhibit/activate one of four pathways:
- AMP-activated protein kinase (AMPK)
- Insulin/ Insulin Growth Factor
- mTOR
- Sirtuins

AMPK- When cellular energy is low, AMPK is activated. AMPK has the ability to combine some signaling and transcriptional pathways known to promote longevity. While the direct role of AMPK in aging is unclear, activating AMPK is sufficient to extend lifespan in model organisms.

Insulin/ Insulin Growth Factor- IGF-1 is a risk factor in several tumors due to its proliferative activity. In C. Elegans, when IGF-1 signaling is lost (by knocking out the receptor, DAF2) worms have an extended lifespan. This down-regulation has been found to prolong lifespan.

mTOR (target of rapamycin)- By inhibiting mTOR, one can upregulate autophagy and possibly suppresses the senescence phenotype. Senescence is when damaged cells decide to stick around. Therefore mTOR increases the rate of clearance of damaged cellular components, essentially junk.

Sirtuins- The 7 sirtuins in humans are believed to protect against deterioration and diseases. Sirtuins basically sense when we’re hungry/exercising, and send out the troops to defend. When you put more sirtuins into a yeast cell or a mouse, it lives 5-20% longer.

When studying these pathways, it is important that scientists study long-lived mutants (not short-lived) in order to look for ways to increase lifespan and healthspan.

Can we solve aging?

@davidasinclair “It’s a matter of when, not if.”

Applying findings from mouse studies, there are several proposed interventions on how to slow down (maybe even eventually stop?) the rate of human aging. Here are a few:

1. Calorie restriction
Low levels of insulin and IGF-1, two factors activating mTOR, induced by caloric restriction are associated with a health span improvement and longevity increase. One of the best things you can do to increase your chances of living longer: don’t overeat.

2. Metformin- Metformin is a drug that activates AMPK and inhibits mTOR, resulting in a decrease of oxidative damage accumulation. Metformin mimics some of the benefits of CR, such as improved performance, increased insulin sensitivity, and reduced cholesterol levels.

3. Resveratrol- Resveratrol affects the activity of enzymes called sirtuins. Sirtuins control several biological pathways and are known to be involved in the aging process. Additionally, it activates AMPK, a potential action to promote longevity and healthy aging

4. Nicotinamide Mononucleotide (NMN)- NMN is a sirtuin-activating compound that increases the activity of sirtuins.

@davidasinclair- “You can think of resveratrol as the accelerator pedal for the sirtuin genes, and NMN as the fuel.”

5. Parabiosis- In mice, parabiosis is a surgical union that allows blood to flow between two mice. The blood from the younger increases lifespan in the older mice. In humans, perhaps there are a few key factors that can be isolated to convey the “parabiosis effect” in the elderly

The ideas here have been simplified and much of it is still being studied.

Both @LauraDeming and @ArtirKel have written informative beginner guides to longevity research that expound more on these interventions: https://www.ldeming.com/longevityfaq  https://nintil.com/longevity/ 

Why should you care about longevity research?

Aging is a threat to the healthcare system. A lot of money is spent on the older population.... We need to care about old people before they get old!

“The way doctors treat illness today is simple. As soon as a disease appears, attack that disease as if nothing else is present; beat the disease down, and once you succeed, push the patient out the door until he or she faces the next challenge. Repeat until failure.”