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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?

Apr 14

Encephalon # 68 carnival, which covers neuroscience and psychology  is up at Ourborous. Chris uses a nice question and answer format for presenting the various submissions.

There are a couple of submissions I would like to point out. Daniel Lende at neuroanthropology takes a critical look at the recent popularity of research examining how poverty affects the brain.

Sandy G at mousetrap discusses an evolutionary theory of how low mood might lead people to become risk averse to avoid further loses. This also suggests that a series of personal failures would lead to risk averse behavior, and hence depressive like symptoms.

Don’t just accept my limited selection, go check out the entire carnival.

The aging and longevity blog carnival, Hourglass, will be coming online today at Psique (updated: here is the link) which is written by Laura Kilarski. I am looking forward to her write up, so check out her blog later today for the 9th edition of the hourglass carnival.

Dec 11
Transmission electron micrograph of a myelinat...
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The progressive loss of myelin as we age is now thought to be an important component of brain aging (see here) - so the last thing you want is to take a drug that might interfere with the turnover and remyelination that occurs naturally (though at a reduced level as we age). The new paper I discuss below indicates the widely prescribed drug statin may inhibit myelination - which could have serious consequences for the aging brain.

Statins are prescribed for a large group of patients at risk for cardiovascular disease (CVD) to improve blood lipid profiles - and hopefully lower their chance of CVD. In 2004 it was estimated that more than 25 million people worldwide are taking statins (probably far higher numbers now).

Previously, I wrote a piece  (is long-term statin use bad for your long-term health) suggesting that there could be long term negative consequences of statin use. The post basically described a paper that indicated statins pushed glial progenitor cells into differentiating into oligodendrocytes. The concern is that the faster rate of differentiation of progenitors cells into mature cells may lead to the ‘running out’ of progenitors when we get older.

The new paper by Klopfleisch et. al., 2008 wanted to more directly examine the effect of statins on myelin formation. Interestingly, statins, due to its anti-inflammatory function, has been tested clinically for multiple sclerosis - a progressive demyelinating disease (Volmer et. al., 2004). However, the results presented below raises concern for the use of statins to treat a demeylination disease.


First the group looked in vitro and found that statins reduced activated p21Ras and its downstream target Erk1/2 by 60-65% in oligodendrocytes. Additionally, Rho-A and ROCK activity was increased by 150-170% (interestingly, these two molecules are also important to axonal regeneration/growth). Previous work had indicated that inhibition of ROCK activity resulted in increased oligodendroglial process formation (indicating a move toward remyelination). Therefore, the increased ROCK activity observed with statin application suggested the possibility of decreased myelination (which the authors were not suspecting).

Now, with their surprising in vitro findings the researchers moved to an in vivo model to test how statins might effect myelination. Mice were fed cuprizone which results in demyelination of the corpus callosum. When you stop feeding the animals cuprizone there is spontaneous remyelination of this same brain region.

Long story made short is the animals that additionally received statins had significantly worse remyelination (both percentage of axons remyelinated and degree of myelination as measured by g-ratio, and measurements of the key components of mature myelin: e.g. myelin basic protein) compared to the control group.


While statins improves outcome of animal models of MS called EAE and also has been tested clincally in humans (though not sure on the current clinical use of statins for MS) this paper raises some concerns for the long term use of statins. The author addresses these issue in their discussion suggesting that the anti-inflammatory action of statins may help MS at one level and produce favourable results - but their work still raises a concern of statins negative effect on remyelination.

However, what I am more interested in is that there is growing awareness that the loss of white matter (myelin) which is composed of oligodendrocytes wrapping of axons is an important component of brain aging (review article). If as described in the above paper taking the statin drug result in reduced spontaneous remyelination what would this mean to the aging brain. Throughout life there is spontaneous remyelination as part of a normal turnover and repair process. As we age there is probably more myelin loss and a reduced ability to spontaneously remyelinate. What would be the result of long-term use of the statin drugs you are taking to reduce your cardiovascular risk? Would it be a reduced rate of spontaneous remyelination and hence an overall increase of demyelination - and would this then increase the rate of cognitive decline which is observed with age induced loss of white matter?

It appears we need to take a closer examination of statins effect in brain aging studies (first in animals - though we could investigate deceased human brain samples and compare chronic statin users versus non-users) to get a more complete picture.

Another obvious answer is to make sure you are doing all the things possible that you have control over, such as exercise and healthy eating so you do not fall into the group with serious CVD risk factors and therefore have no need to take statins (or other similiar drugs).

Update: I recently posted about a paper which suggest that statin use reduces the risk of dying (from all causes of death).

Update II: maybe statins do not decrease mortality

Nov 27
DNA damage, due to environmental factors and n...

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A new paper just out in Cell by the Sinclair group gives us some intriguing but sobering information about aging and genomic integrity.

The new twist to the ever evolving story is the Sirt1 protein might have at least two primary roles in the cell. The first role is to locate itself on DNA to inhibit these particular genes that it is situated on for they are not needed by this particular cell at this time. The second role though is to help repair DNA damage caused by such things as oxidative stress. Sirt1 leaves its original location in which it was suppressing specific genes to where the DNA is damaged and hence they are no longer doing their gene suppressing job.

As the short review article in Science pointed out - this is a catch-22 situation (the catch-22 of aging).

In the paper when they induced oxidative stress there was a Sirt1 dependent dsregulation of gene expression - which resembles that of an aging mouse brain (see below). With the oxidative stress Sirt1 was relocated (from its original sites of action) to the DNA double-strand breaks. If Sirt1 was reduced there was less efficient repair of these DNA breaks. Interestingly, overexpression of Sirt1 repressed 85%  of the formerly deregulated gene expression.

Next the researchers irradiated mice to induce cancer in a specific mouse strain prone to developing cancer (p53 +/-) and found the Sirt1 activator resveratrol if fed 3 weeks prior to the irraditation increased survival by 24%. Since resveratrol might not be just working through increased Sirt1 activity they used a transgenic aniamal that allowed temporal and tissue specific overexpression of Sirt1. A 2-4 fold increase of Sirt1 expression in bone marrow lymphocyte progenitors and mature B and T cells was induced 2 weeks prior to exposure of the mice to irradiation. Survival in the Sirt1 induced animals increased by 46%. Finally, they found that overexpression of Sirt1 in the mouse brain could repress the age related deregulation of certain genes.

I am only give you brief outline of the paper, I encourage you to read the full thing if you are a scientist for even if this is not your particular scientific interest it is thorough and involves many interesting techniques.

Take home messages:

Aging could be a catch-22 situation - Sirt1 steadfastly performs its normal function of suppressing inappropriate gene expression but when there is DNA damage it abandons the castle to fight off genomic instability - but at the cost of deregulation back on the home front. However, overexpression of Sirt1 (via resveratrol and/or more direct genetic manipulations) can at least partially rescue the adverse affects of the accelerated irradiation induced ‘aging’ (genomic instability - increased cancer). Think of it as if you have enough soldiers you can both defend the home castle and fight wars in far off lands (though I am not a big fan of war like analogies).

Remember dietary restriction (in the form of calorie restriction or every-other-day fasting) has been reported to increase Sirt1 expression and dramatically decrease the incidences of cancer (tested numerous ways including radiation induced cancer), and increase genomic stability. Sounds famliar doesn’t it.