A List of 15 Compounds to Extend Lifespan

Not so long ago I discovered a crowd-funded project on longevity. A Ph.D. student from U.S.C. and her team decided to write a comprehensive book called Longevity Cookbook. The project has been successfully funded about a year ago (~$58,000). The book is in the making.

Earlier this year, in March 2016, they had published their first chapter for free online. In it they talk about the current pharmacological means that we could use to increase longevity. It's a long-read and my purpose here is to give you the short summary.

15 Compounds for Lifespan Extension

1. Bisphosphonates

• to prevent bone mass loss
• used as industrial water softeners, they help prevent the precipitation of calcium carbonate
• in living organisms they could inhibit osteoclasts (cells that degrade bone tissue)

2. Rapamycin

• it targets mTOR, a nutrient sensing pathway
• when mTOR is off, cells become more resistant to stress
• mTOR off - lifespan increase in many organisms
• mTOR - mostly turned on by protein intake

3. Ubiquinone (Q10)

• for higher redox potential

In the mitochondria of your cells, Q10 works as an electron acceptor, thus protecting against free radical damage

• Q10 products are still not as good as desired (poor absorbability), but better ones are coming to the market

4. Metformin

• for higher insulin sensitivity: reduces liver gluconeogenesis (production of glucose in the liver)
• it's positively associated with increased lifespan and healthspan in many animal models and in humans
• it's cheap and it can be obtained without prescription in many countries

5. Aspirin

• it inhibits COX1 and COX2 => reduction of pain and inflammation
• it has been shown to inhibit cancer development (different forms)
• it has been shown to reduce heart attack risk
• positive effects on lifespan in animal models

6. Ibuprofen

• it has been shown to reduce the risk of developing Alzheimer's by 40%
• it has been shown to reduce the risk of developing Parkinson's by 30-40%
• positive association with median lifespan in model organisms

7. Acarbose

• reduces after-meal blood glucose levels; anti-diabetes medication
• well tolerated by most people
• positive association with lifespan extension in mice
• potential drawback: 78% of the subjects who use it have increased flatulence

8. 17-a-estradiol

• non-feminizing estrogen
• confers protection to the brain and the mitochondria
• positive association with lifespan in mice (males, not females)

9. NDGA (Nordihydroguaiaretic acid)

• positive association with lifespan in animal models
• major drawback: in humans it's associated with higher liver toxicity

10. STACs - Sirtuin Activating Compounds

• Sirtuins have been associated with extended lifespan in model organisms
• activating Sirtuins simulates caloric restriction
• resveratrol (from red wine) activates Sirtuins, but it may have poor absorbability
• there are new, more efficient, compounds in the making (for activation of sirtuins)

11. Alagebrium (ALT-711)

• some claims suggest it could reverse age related damage
• possible mechanism of action: breakdown of advanced glycation end products (AGEs)
• it is currently not under active development

12. Lithium

• it has been shown to offer brain protection in animal models
• it may work by reducing inflammation and increasing new neuron creation
• BPD (bipolar disorder) patients who use lithium have thicker cortex and more grey matter compared to patients who don't use it

13. Glucosamine

• it may inhibit glycolysis => creates energy deficit => increases mitochondrial biogenesis
• it has been positively associated with higher lifespan in animal models

14. C60 Fullerenes

• 60 carbons bound together make up a Buckminsterfullerene (C60)
• adding carboxyl groups to C60 => formation of SOD (superoxide dismutase) mimetics - a part of the cellular defense system

15. Telomerase Activators

• telomeres are like end caps on chromosomes inside the cell nucleus
• when cells divide, they shorten
• when they get too short, the cell stops dividing (becomes senescent)
• telomerase (an enzyme) lengthens telomeres => more cell division

As I wrote in the past:

"Some propose that telomere lengthening could increase lifespan. Thus, using telomerase activators would make sense. There is a big debate on this topic since one may not want to indiscriminately increase telomerase activity (think of cancer cells). Studies have been conducted with mixed results."

My Thoughts

Aging is a very controversial topic and it's not easy to find good data about it. There's a lot of misinformation (on purpose) especially with the whole detox/cleanse/rejuvenation fads. But as a scientific field, it starts getting more active interest from serious researchers.

Still, it's hard to get human data on aging because it's not easy to carefully conduct long term research studies. That's why we currently mostly rely on data from animal models, which have shorter lifespan.

From a metabolic perspective though, healthy lifespan has been associated with the following:

• lower mTOR
• lower insulin and IGF-1
• higher AMPk activity
• lower T3 levels (active thyroid hormone)
• lower growth hormone activity (mixed results)
• and a few others.

For that matter, my current personal interventions are:

• nutrient rich caloric restriction
• protein restriction
• fasting and intermittent fasting
• frequent intense exercise
• use of supplements like alpha lipoic acid

I also experimented with metformin and I was pleased with the results in term of higher ketosis, higher satiety and better gut function (motility).

NMN (the future of sirtuin activation) is one compound that I'm very excited about.

If you have questions or additions to this list, leave me a comment below.

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Credits for Images: Katy Tresedder

#extreme #longevity #science

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Cristi Vlad, Self-Experimenter and Author