j-147 - The Anti-Aging Nootropic?
As you take a deep dive into the world of nootropics, you begin to see that not all nootropics are created with equal benefits and applications. For example, some might promote sleep or relieve anxiety, while others act as stimulants or provide laser focus. Even then, they will act on different neurotransmitters such as dopamine, adrenaline, or serotonin ro name a few so truly this is a category with a vast scope. However, one relatively new frontier in the field is looking at their anti-aging effects.
After puberty, the brain is fully developed and ages from this point onwards. The point of actual decline may begin in your 20s or 30s in some individuals. This can be accelerated or slowed by the lifestyle choices we make, such as alcohol, drugs, sleep, and stress. While cycloastragenol is highly regarded in the anti-aging field for its ability to combat inflammation and age related shortening of telomeres, this is only one of the ways in which aging causes a deterioration in physical and cognitive status.
One new compound which has been investigated as a potential anti-aging compound is J-147 and it works in a completely different way to cycloastragenol. Here’s what we know about it so far.
What is J-147 and how does it work?
J-147 is derived from curcumin, the active ingredient in turmeric. Unlike curcumin, it can cross the blood-brain barrier very successfully.
J-147 works by binding to ATP synthase. The overproduction of ATP has links to the aging process. J-47 can control this in addition to increasing levels of the neurotransmitters NGF and BDNF.
Several studies with J-147 have been conducted in mice. A human trial was carried out in 2020, however, full results have not yet been shared.
J-147 and Dementia
Mice with rapidly aging brains were treated with CMS121 and J147. The researchers found that it reduced cognitive decline as well as metabolic and transcriptional markers of aging in the brain. Both compounds preserved mitochondrial homeostasis by regulating acetyl-coenzyme A (acetyl-CoA) metabolism. CMS121 and J147 increased the levels of acetyl-CoA in cell culture and mice via the inhibition of acetyl-CoA carboxylase 1 (ACC1), resulting in neuroprotection and possible memory enhancement. 
Another mouse study found that, by targeting ATP synthase, J147 causes an increase in intracellular calcium leading to sustained calcium/calmodulin-dependent protein kinase β (CAMKK2)-dependent activation of the AMPK/mTOR pathway, a canonical longevity mechanism. 
J-147 and Diabetic Neuropathy
Diabetic peripheral neuropathy is a condition where nerve damage occurs as a result of chronically raised blood glucose levels, as can be seen in poorly managed diabetes. J-147 may help treat this complication.
In rats, it was concluded that J147 could ameliorate DPN via negative regulation AMPK on TRPA1 in vivo and in vitro. J147 has been suggested as an alternative to the polypharmaceutical approaches required to treat the multiple pathogenic mechanisms that contribute to diabetic neuropathy. 
J-147 and Depression
J-147 has been investigated for anti-depressant-like effects. This seems to work through 5-HT 1A-mediated cAMP signaling, with improvements seen in rats in just 3 days. In another rat study, up-regulated pCREB and BDNF levels lasted for 3h after 10 mg/kg of J147. 
Benefits of J-147
- Improves mitochondrial function and longevity
- Improves memory and cognition
- May help neurogenesis
- Might improve anxiety symptoms
J-147 Risks and Side Effects
J-147 successfully passed the toxicology testing in animal trials as required by the Food and Drug Administration (FDA), and no negative effects have been reported in humans when taken at an appropriate dosage (discussed later).
J-147 - A Personal Review
I have been using J-147 now for several weeks in conjunction with IDRA-21, also by Limitless Nootropics. While running both concurrently does make it more difficult to identify what benefit is coming from which, the benefits of IDRA-21 and J-147 seem to complement each other well for the effect I wanted (mental clarity and enhanced focus without stimulation).
I have been very happy with the results I’ve seen from using J147. As a healthy adult in my 20's, I wasn’t expecting a dramatic effect, but the neuroprotective benefits and the possibility that this supplement will allow me to continue to perform at my best in work and learning into old age was enough to sell me.
I have stuck to 10mg per day, taken after my first meal, throughout my experience of using the supplement. I have not had any negative side effects and would be keen to keep this in year-round for longevity reasons!
I would keep the supplements that you take alongside this simple. A high quality fish oil would be a great start for brain health!
J-147 Dose and Stacking Guide
A typical daily J-147 dosage lies between 5mg and 30mg, with Limitless Nootropics opting for 10mg per capsule. Limitless recommend starting with one capsule daily, which you may then progress to a second capsule midday for a total of 20mg. It is not recommended to take it late at night, and there is no data yet on whether it needs to be cycled. J-147 has a half-life of 2.5 hrs in the brain, hence the logic in splitting dose if using over 10mg.
Some of the benefits will become apparent quickly once you begin use. In mice, J-147 induces rapid antidepressant-like effects during a 3-day treatment period without inducing drug tolerance and increased cognition even with short-term treatment.
J147 has not been popular amongst healthy individuals for long enough for us to confidently recommend any stacks. Not all nootropics can be ‘mix and matched’ safely.
J-147 is one of the most promising anti-aging nootropics around right now. While it might not be the best choice when taken alone for wakefulness or motivation, it is an excellent one to take long-term for the longevity benefits it might bring about. We would also strongly recommend it for older nootropic users.
 Currais, A., Huang, L., Goldberg, J., Petrascheck, M., Ates, G., Pinto-Duarte, A., Shokhirev, M., Schubert, D. and Maher, P., 2019. Elevating acetyl-CoA levels reduces aspects of brain aging. eLife, 8.
 Goldberg, J., Currais, A., Prior, M., Fischer, W., Chiruta, C., Ratliff, E., Daugherty, D., Dargusch, R., Finley, K., Esparza-Moltó, P., Cuezva, J., Maher, P., Petrascheck, M. and Schubert, D., 2018. The mitochondrial ATP synthase is a shared drug target for aging and dementia. Aging Cell, 17(2), p.e12715.
 Lv, J., Cao, L., Zhang, R., Bai, F. and Wei, P., 2018. A curcumin derivative J147 ameliorates diabetic peripheral neuropathy in streptozotocin (STZ)-induced DPN rat models through negative regulation AMPK on TRPA1. Acta Cirurgica Brasileira, 33(6), pp.533-541.
 Daugherty, D., Marquez, A., Calcutt, N. and Schubert, D., 2018. A novel curcumin derivative for the treatment of diabetic neuropathy. Neuropharmacology, 129, pp.26-35.
 Li, J., Chen, L., Li, G., Chen, X., Hu, S., Zheng, L., Luria, V., Lv, J., Sun, Y., Xu, Y. and Yu, Y., 2020. Sub-Acute Treatment of Curcumin Derivative J147 Ameliorates Depression-Like Behavior Through 5-HT1A-Mediated cAMP Signaling. Frontiers in Neuroscience, 14.
 Lian, L., Xu, Y., Zhang, J., Yu, Y., Zhu, N., Guan, X., Huang, H., Chen, R., Chen, J., Shi, G. and Pan, J., 2018. Antidepressant-like effects of a novel curcumin derivative J147: Involvement of 5-HT1A receptor. Neuropharmacology, 135, pp.506-513.