https://t-nation.com/t/healthspan-the-new-caffeine-connection/291475

Healthspan: The new caffeine connection
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Healthspan: The new caffeine connection
articles,diet-nutrition,indigo-3g

T_Nation 11

Activate a certain enzyme in your body and you’ll live longer and look better. Here’s a buzzy way to do it.
If you’re a person who likes to dig deeper into the science of building muscle, losing fat, and increasing healthspan, then you know about AMPK, your body’s powerhouse enzyme. AMPK is like a master switch that senses when energy levels are low and flips on processes to keep things running smoothly. Here’s a quick refresher:
- AMPK signals your body to produce more ATP (the body’s energy currency) by burning fats and sugars more efficiently. It activates fat breakdown to use stored fat as fuel.
- AMPK helps cells respond better to insulin and lowers blood sugar levels, supporting metabolic health.
- AMPK boosts mitochondrial production, providing energy for muscle contractions. It also activates pathways like mTOR, which helps build muscle.
- AMPK dials down inflammatory signals in the body, which can damage tissues and cause chronic diseases.
- AMPK activates stress response pathways, which protect cells from damage and slow aging. That helps increase lifespan and reduce age-related diseases.
Endurance and high-intensity workouts (HIIT) activate AMPK naturally, as does severe calorie restriction, but that’s no fun. Drugs like metformin do too, but they can cause conditions like lactic acidosis, and they interfere with training-induced muscle protein synthesis.
What else can we do to activate AMPK? A recent study came across something new: consuming caffeine.

The study
This study, published in Microbial Cell, investigates how caffeine affects cell cycle regulation, DNA damage sensitivity, and chronological lifespan in fission yeast.
Wait, yeast? Yep. Fission yeast shares key cellular pathways with humans, such as AMPK, TORC1, and cell cycle regulation, which control energy, growth, and DNA repair. In short, yeast reliably models human biology, plus it’s fast and ethical to use in studies.
The study gets complex, with mind-melting terms like Ssp2 phosphorylation, Rad3 inhibition, and Cdc25 stability. So let’s jump to what they discovered and its implications for us:
- Caffeine activates AMPK.
- Fission yeast cells exposed to caffeine had a longer lifespan, up to 24%.
- Cells aged more slowly and became more resistant to genetic damage.
- Caffeine’s modulation of AMPK mirrors the effects of metformin.
- For humans, moderate caffeine intake (roughly 200-400 mg) activates similar pathways.
If you’re already taking a preworkout like Biotest Igniter (Buy at Amazon), you’re covered.

What else activates AMPK?
C3G (cyanidin-3 glucoside) is a powerful AMPK activator. This anthocyanidin, found in dark berries and black rice, works as well or better than prescription glucose-disposal drugs and doesn’t interfere with protein synthesis.
How? Well, get ready for some more mind-melting terminology. C3G raises AMPK levels primarily by stimulating CaMKKβ to phosphorylate AMPK at Thr-172, amplified by mimicking energy stress (higher AMP/ATP ratio). This activates AMPK, which then modulates downstream targets like ACC to enhance energy efficiency.
Here’s all you really need to know: Activating AMPK leads to a longer, healthier life with more muscle and less body fat. Exercise, caffeine, and C3G activate AMPK. So enjoy your coffee and take supplemental C3G, found in Indigo-3G Nutrient Partitioning Agent (Buy at Amazon). Take 4 capsules about 30 minutes before your largest meal of the day.

Note: Indigo-3G is now formulated with glycerol monostearate (GMS) to enhance the absorption and bioavailability of C3G.
Reference
- Alao, John-Patrick, et al. “Dissecting the Cell Cycle Regulation, DNA Damage Sensitivity and Lifespan Effects of Caffeine in Fission Yeast.” Microbial Cell, vol. 12, no. 6, 24 June 2025, pp. 141-156, doi:10.15698/mic2025.06.852


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