July 27, 2006
Ampakines Reverse Brain Aging In Rats

Ampakines reverse some aspects of brain aging in rats.

A drug made to enhance memory appears to trigger a natural mechanism in the brain that fully reverses age-related memory loss, even after the drug itself has left the body, according to researchers at UC Irvine.

Professors Christine Gall and Gary Lynch, along with Associate Researcher Julie Lauterborn, were among a group of scientists who conducted studies on rats with a class of drugs known as ampakines. Ampakines were developed in the early 1990s by UC researchers, including Lynch, to treat age-related memory impairment and may be useful for treating a number of central nervous system disorders, such as Alzheimerís disease and schizophrenia. In this study, the researchers showed that ampakine drugs continue to reverse the effects of aging on a brain mechanism thought to underlie learning and memory even after they are no longer in the body. They do so by boosting the production of a naturally occurring protein in the brain necessary for long-term memory formation.

I am surprised this was so easy to do. Some aspects of brain aging will require gene therapy, cell therapy, and other techniques to reverse. But this study's results strongly suggest that conventional drugs will play an important role in preventing and reversing brain aging.

Ampakines boosted a protein involved in memory formation and improved quality of connections between nerve cells.

The researchers treated two groups of middle-aged rats twice a day for four days with either a solution that contained ampakines or one that did not. They then studied the hippocampus region of the ratsí brains, an area critical for memory and learning. They found that in the ampakine-treated rats, there was a significant increase in the production of brain-derived neurotrophic factor (BDNF), a protein known to play a key role in memory formation. They also found an increase in long-term potentiation (LTP), the process by which the connection between the brain cells is enhanced and memory is encoded. This enhancement is responsible for long-term cognitive function, higher learning and the ability to reason. With age, deficits in LTP emerge, and learning and memory loss occurs.

Significantly, restoration of LTP was found in the middle-aged ratsí brains even after the ampakines had been cleared from the animalsí bodies. The drug used in the injections has a half-life of only 15 minutes; the increase in LTP was seen in the ratsí brains more than 18 hours later. According to the researchers, this study suggests that pharmaceutical products based on ampakines can be developed that do not need to be in the system at all times in order to be effective. Most drugs used to deal with central nervous system disorders, such as Parkinsonís disease, are only effective when they are in the body. Further studies will be needed to determine exactly how long the effect on LTP will be maintained after the ampakines leave the system.

The economic impact of drugs that reduce and reverse brain aging will be huge. People in their 50s, 60s, and 70s will be far more economically productive when brain aging can be reduced and even reversed. The question isn't whether this can be done but when it will be done.

Share |      Randall Parker, 2006 July 27 11:39 PM  Aging Reversal

James Bowery said at July 28, 2006 7:37 AM:

What is the FDA status of ampakines?

Nick said at July 28, 2006 8:32 AM:

Yes, any data on safety??

PacRim Jim said at July 28, 2006 10:52 AM:

What was the name of that drug again?

rsilvetz said at July 28, 2006 1:02 PM:

Well, they are derivatives of benzylpiperidine, which frankly, I would have expected to be a poison.

So, yeah, let's have the safety data and use them if they aren't too toxic. (Will trade small liver hit for large brain boost!)

Brett Bellmore said at July 28, 2006 3:42 PM:

Sounds like great stuff, assuming the government ever permits us to have it.

Kelly Parks said at July 28, 2006 11:05 PM:

Isn't this the same stuff as Provigil / Modafinil? They only seem to be available from internet pharmacy sites.

Lou Pagnucco said at July 29, 2006 11:46 AM:

A quick web search yields a few other approaches to increasing BDNF:
- stress reduction
- physical and mental exercise
- most antidepressants
- diets restricting saturated fats and sugars
- omega-3 fatty acids
- lithium
- Long-Term Repetitive Transcranial Magnetic Stimulation
- caloric restriction
(BTW, I found an interesting short presentation on brain development, aging and plasticity at

There are also references to nasal spray delivery of ampakines online.

Randall Parker said at July 29, 2006 2:01 PM:


Thanks for that.

Omega 3 fatty acids: I eat salmon a couple of times a week solely to get omega 3's.

Not surprised by the antidepressant result. Selective Serotonin Reuptake Inhibitors (SSRIs) such as Paxil, Prozac, and Zoloft are known to increase neural stem cell division.

Curiously, omega 3's also have an antidepressant effect. Would a BDNF boosting drug act as an antidepressant? Probably.

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