Researchers find that Sirtuin1 may boost memory and learning ability

Jul 11, 2010
Crystallographic structure of yeast sir2 complexed with ADP and a histone H4 peptide.

The same molecular mechanism that increases life span through calorie restriction may help boost memory and brainpower, researchers at MIT's Picower Institute for Learning and Memory report in the July 11 issue of Nature.

Resveratrol, found in wine, has been touted as a life-span enhancer because it activates a group of enzymes known as sirtuins, which have gained fame in recent years for their ability to slow the aging process. Now MIT researchers report that Sirtuin1 — a protein that in humans is encoded by the SIRT1 gene — also promotes and brain flexibility.

The work may lead to new drugs for Alzheimer's disease and other debilitating .

"We demonstrated previously that Sirtuin1 promotes neuronal survival in age-dependent neurodegenerative disorders. In our cell and mouse models for Alzheimer's disease, SIRT1 promoted neuronal survival, reduced neurodegeneration and prevented learning impairment," said Li-Huei Tsai, director of the Picower Institute and lead author of the study.

"We have now found that SIRT1 activity also promotes plasticity and memory," said Tsai, Picower Professor of Neuroscience and a Howard Hughes Medical Institute investigator. "This result demonstrates a multi-faceted role of SIRT1 in the brain, further highlighting its potential as a target for the treatment of neurodegeneration and conditions with impaired cognition, with implications for a wider range of disorders."

In separate work at MIT, researchers discovered that the sir2 (silent information regulator) gene is a key regulator of longevity in both yeast and worms. Ongoing studies are exploring whether this highly conserved gene also governs longevity in mammals.

The mammalian version of the gene, SIRT1, seems to have evolved complex systemic roles in cardiac function, DNA repair and genomic stability. SIRT1 is thought to be a key regulator of an evolutionarily conserved pathway that allows organisms to cope with adversity. These genes and the enzymes they produce are part of a feedback system that enhances cell survival during times of stress, especially a lack of food.

Recent studies linked SIRT1 to normal brain physiology and neurological disorders. However, it was unknown if SIRT1 played a role in higher-order brain functions.

The Picower Institute study shows that SIRT1 enhances synaptic plasticity, the connections among neurons, and memory formation. These findings demonstrate a new role for SIRT1 in cognition and a previously unknown mechanism by which SIRT1 regulates these processes.

MicroRNAs are small RNA molecules encoded in the genomes of plants and animals. These gene regulators are involved in many aspects of normal and abnormal brain function. The Picower study found that SIRT1 aids memory and synaptic plasticity through a previously unknown microRNA-based mechanism: SIRT1 keeps a specific microRNA in check, allowing key plasticity proteins to be expressed.

In addition to helping neurons survive, SIRT1 also has a direct role in regulating normal brain function, demonstrating its value as a potential therapeutic target for the treatment of the central nervous system.

Explore further: How nerve cells communicate with each other over long distances

More information: "A novel pathway regulates memory and plasticity via SIRT1 and miR-134," Jun Gao Wen-Yuan Wang, Ying-Wei Mao, Johannes Gräff, Ji-Song Guan, Ling Pan, Gloria Mak, Dohoon Kim, Susan C. Su and Li-Huei Tsai, in the July 11 issue of Nature. www.nature.com/nature/journal/… ull/nature09271.html

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User comments : 9

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Birger
3 / 5 (2) Jul 11, 2010
We need genetically modified plants with genes to boost their output of Resveratrol. That way we can provide it at a scale sufficient to use it as a food additive.
docjape
5 / 5 (3) Jul 11, 2010
'...Hunger concentrates the mind!...'
prash_n_rao
not rated yet Jul 11, 2010
odd... this directly contradicts a previous report released in some other journal just this month!

http://www.physor...331.html
bottomlesssoul
not rated yet Jul 11, 2010
I think this isn't about hunger per se but sustained stress when the body is making serious decisions about what to sacrifice over weeks of stress. I guess the disabling brain plasticity during famine is an unsuccessful experiment. What I find surprising is during this stress plasticity is favored because it's so biologically expensive.

I get it if the stress were coming from chasing down prey. High levels of exercise are known to favor brain plasticity and it makes sense because at the end of the day there is more food (in a normal environment).

I wonder if they share the same circuit or are they different and so possibly additive? Does exercise and resveratrol favor higher plasticity than either alone?
GaryB
4.5 / 5 (2) Jul 12, 2010
odd... this directly contradicts a previous report released in some other journal just this month!

http://www.physor...331.html


It's all resolved by just drinking more red wine. Even if it doesn't extend life, it will extend pleasant times in life.
Au-Pu
not rated yet Jul 12, 2010
Because these proteins play so many roles perhaps there are other factors that determine the final result. It may be as simple as a surplus or shortage of something else that the researchers have not as yet detected.
But full marks to prash n rao for being on the ball
kevinrtrs
1 / 5 (2) Jul 12, 2010
SIRT1 is thought to be a key regulator of an evolutionarily conserved pathway that allows organisms to cope with adversity


Does this mean that previously "junk DNA" is now suddenly coming into use? Will some expert please enlighten us? Thanks.
Skeptic_Heretic
not rated yet Jul 12, 2010
Does this mean that previously "junk DNA" is now suddenly coming into use? Will some expert please enlighten us? Thanks.
Care to define "junk" DNA for us as you understand it? I'll be happy to answer your question once I know to what you are referring.
Djincs
not rated yet Jul 17, 2010
We need genetically modified plants with genes to boost their output of Resveratrol. That way we can provide it at a scale sufficient to use it as a food additive.

I agree but now gm is used for the purpous of the profit, it can help to develop even heltier foods but the majority of the people are so convinsed in how bad gm is that even if crops produsing more good stuf is developed, people wont buy it....