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May 27
Drawing of Purkinje cells (A) and granule cell...
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I have written previously about it is all about information and energy, when talking about life and the brain.

Well, I came across a poster that provided some raw data regarding this subject at the Canadian Neuroscience meeting.

The lead author was C. Howarth, and the senior author, Attwell. This group was trying to calculate the energy and information cost of Purkinje cells, which are found in the cerebellum. Their conclusion was this:

… for each Purkinje cell (and associated other neurons and glia) approximately 10 to the 11th power molecules of ATP/s are used per 5 kb of retrievable motor information, corresponding to an information storage cost of 1 mW/Gb.

Now off the top of my head I don’t know how this compares with the computers of today, and don’t have the time today to look it up, for I need to head to the last day of the conference. But I sometime find this type of data a good reminder (though I shouldn’t need one) is that our brain is just a processor of information from the outside and inside environment for the purpose of enhancing our survival and propagation.

Maybe someone with more in-depth knowledge of computers/information processing could compare and contrast this above neuronal data with computers.

May 25

I wrote a post last week about, what to do with your peak 5 years? In it I wondered if we need to identify when the average person peaks in various endeavors; from sports, musical playing ability, to numerous mental specialties.

If you asked me in my early 20s when does peak in mental abilities occurs I would have said mid to late 20s. Maybe I tied the physical with the mental a little too much (not to mention over the last 20 years we see many athletes peaking in their mid to late 30s). The question is when do we reach our peak mentally?

Hedden and Gabrieli 2004, in a very nice Nature Reviews Neuroscience article, provide an informative graph of a longitudinal study on mental ability as we age (which in this case provide more interesting data than a cross-sectional study).

You can see that perceptual speed has the quickest drop off as we age. An example of perceptual speed would be you are given a large square of numbers (20 X 40) and you are asked to circle all the 6s as fast as you can. You have to scan the numbers quickly, identify all the 6s, and circle them. And yes from 25 onwards it is all downhill. This might have been the raw processing ability I was thinking about when I was in my early 20s, that quickness - mental and physical.

Numeric ability starts dropping around the age of 39. Though mathematics is far beyond ‘numeric ability’ this general math decline goes along with the long held notion in the mathematical world that very few math breakthroughs occur in people beyond their 30s (e.g. mathematics is a young man’s game - see “A Mathematician’s Apology” - highly recommended for anyone thinking of going into math - or just curious - a classic).

But all the other mental tasks plotted in the graph; inductive reasoning, spatial orientation, verbal ability, and verbal memory, continue to increase for people in their 30s and 40s - and peaking in the 50 to 60 year old range.

Now of course these listed mental abilities are not all inclusive, but you get the general idea, which is for many mental abilities the peak might be far later than you normally thought.

Take home message:

If you are in your 20s or 30’s you can look forward to continued improvement in many, but not all, of your mental abilities. For those in your 40s or 50s you still can look forward to your ‘peak’ but you better prepare to take advantage of this apex. As for those in your 60s or later, you need to remember the data from the above graph is the ‘average’ there are still going to be many that peak at a later point in their life. The trick is to make sure you look after yourself (eat right and exercise would be a good start) so you can maintain, or even continue to improve, your mental ability as you age.

And why does knowing when the average peak mental ability occur matter - see - What to do with your peak 5 years?

May 21
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I have previously written a piece about what would you do if given the gift of an extra 5 years, but what about using your ‘peak’ years to the best of their possibilities?

What spurred the original idea was from the question of what to do if you only had 5 years left to live, but since I post some pieces on longevity then the question was reformed to, ‘what would you do with an extra 5 years’? In both cases do we fully utilize those 5 years or waste them away?

Now the question is, what to do with your peak 5 years. This could be your 5 peak athletic years, social years, travel years, intellectual years, partying years, work/earning years, musical years, philosophical years,  etc? We all have different priorities. The first question might be on average at what age do peak years usually occur in the various endeavors? I might at another time write a piece that gives some data for various things we would like know when peak years occur. Obviously for most athletic events peak years occur at a fairly young age, but can range from teens for female gymnastics to mid to late 30s for some endurance sports, and other sports such as baseball pitchers. For quite a few intellectual pursuits peak years occur later in life than for athletics (with math tending to be on the young side 20s to mid 30s).

For argument sake let us say we have tons of data and we have a table that shows on average what are the peak 5 years for everything you can imagine, from juggling to classical musical composition (and there would be a bell curve of ages in which this peak occurs for each of these pursuits).

Now with this information from this hypothetical table what would you do? Now a side note is that in most cases to reach our individual peak you have to put in 10,000 hour of deliberate practice (so roughly 6-8 hour per day 350 days per year) for 5 years would get you up to 10,000 hours). I will be writing more about this subject soon.

If you were a drawing artist and you knew that the peak years occurred in your late 20s (and obviously there is going to be a bell curve of ‘peakness’ that might be quite wide ranging) and you are currently 25 would you ponder the idea of dropping everything and spending the next 5 years somewhere, be it in some prototypical artistic city like Paris, or your hometown, and devote yourself to becoming the best artist you can be?

Or you are a 23 year old triathlete would you drop your bank clerk job and go to live your dream of becoming a professional triathlete? At the other end maybe you are 40+ but realize that there are still various intellectual pursuits in which peak years do not occur until late 40s or mid 50s - are you willing to drop your cushy mid profession income, and social position, to take the high risk of trying one of these ‘peak’ endeavors?

How much do you really care about following your dreams, or just keeping your comfortable lifestyle?

You might have or had various dreams in which some of those potential peak years are coming up, and in some cases they might have slipped away. How many more ‘peaks’ are still in front of you? How many can you afford to let pass by? Or you can take pleasure in your comfortable lifestyle and live a normal life - it is your choice.

May 19
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A new paper (Renthal et al., Neuron 2009) that was examining the genome-wide chromatin regulation that occurs in the nucleus accumbens (an important area in the brain for reward) during cocaine addiction turned up some interesting results. The researchers took a closer look at some of the specific changes including sirtuin 1 and 2 (Sirtuins are believed to be involved in the positive effects of the potential longevity treatment resveratrol.)

To manipulate sirtuin 1 and 3 they turned to the widely studied sirtuin activator - resveratrol. Now most of you are probably quite familiar with resveratrol because it is investigated as a potential dietary restriction mimicker to potentially increase life span (see: Resveratrol for better brain health, Resveratrol improves heart health but not lifespan of mice (on normal diet), The testing of a new sirt activator: SRT1720, Sirt1 and aging: fighting wars on two fronts, 60 minutes coverage of potential longevity treatments). Now if increasing sirtuin proteins with resveratrol (or similar derivatives) is a dietary restriction mimicker we might expect some of the same overall positive and negative effects.

A bit of background:

Dietary restriction (DR), in the form of straight calorie restriction (CR), or every-other-day fasting (EODF)(which can also lead to calorie restriction depending on the species), with adequate nutrients, has been reported to increase life span in a wide range of organisms (they have been studying this for 80 years).

Interestingly, a number of studies have demonstrated an increase propensity for addiction in dietary restricted animals (both straight CR, or EODF). When I tell people about dietary restriction I always caution them about the one of the downsides of DR, which is a potential for increased addiction (for review see: Carr 2007). DR appears to notch up the reward system in an attempt to give the organism more incentive, more reward, for going to seek food (and maybe many other rewards). However, with this increase of gain in the reward system, it appears the organism is more easily develops addiction to rewarding drugs. But I also give the flip side that a notched up reward system with CR or EODF may make the average sunset more rewarding.

the question then is resveratrol invokes some of the same positive molecular changes as DR does - since it is hoped to be a DR mimicker - then maybe it makes sense it might also play a role in addiction.

New paper results: Resveratrol and cocaine addiction

Renthal et al., Neuron 2009 among a host of other genes changes with the intake of cocaine found an increased expression of sirt 1 and 2, as mentioned earlier.

We identified Sirt1 and Sirt2 from our ChIP-chip analyses of delta FosB target genes that also were regulated by histone acetylation. We then identified significant increases in both Sirt1 and Sirt2 mRNA and protein activity in the NAc after chronic cocaine administration.

Now having found an interesting target they manipulated it using resveratrol (a sirtuin activator) and an inhibitor of the pathway, sirtinol. Resveratrol increased the rewarding effects of cocaine, and sirtinol (sirtuin inhibitor) decreased the rewarding effect (in the conditioned place preference paradigm). Inhibiting sirtuins with sirtinol also decreased the amount of self administered cocaine by the animals (less addictive). Activating sirtuins with resveratrol increased the electrical excitability of nucleus accumbens neurons and potentiated the rewarding effects of cocaine.

The authors concluded in their discussion:

Thus, sirtuins appear to act downstream of  delta FosB and may contribute
to a positive-feedback loop in which repeated drug exposure
increases levels of delta FosB and sirtuins, which in turn enhances
the motivation to take additional drug. These findings raise the
possibility of using SIRT1/2 inhibitors as potential treatment
agents for cocaine addiction.

So they are talking about inhibiting sirtuins as a treatment for cocaine addiction. Combined with their presented data that resveratrol accentuates cocaine’s reward would suggest that this dietary restriction mimicker may increase the potential for drug addiction (or lower the threshold). This would be consistent with the other similarities that resveratrol and dietary restriction have in common - both good and bad.

Take home message:

Activating the sirtuin pathway either via the intake of the potential pharmaceutical treatment to increase life span resveratrol appears to increase the rewarding effects of addictive drugs, and therefore may increase the potential for addiction (which is similar to the effects of dietary restriction). I guess a word of caution should be noted for anyone contemplating either resveratrol or dietary restriction (know thyself).

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