What a roller coaster ride! The dogma for many years was that the structure of the adult brain was relatively static throughout an individuals life - we were born with all the neurons we were going to have and the circuits those neurons formed during our childhood and teenage years were maintained till death.
Then in 1962 Altman demonstrated neurogenesis in the adult rodent brain. In 1964 Bennett demonstrated how environmental enrichment could increase cortical mass in the adult rodent brain. In 1969 Raisman demonstrated axonal plasticity in the adult rodent brain and in 1984 Purves showed dendritic plasticity in the adult rodent brain. In 1988 reservoirs of brain stem cells were found in the hippocampus and at the lateral brain ventricles. With the discovery of neural and glial progenitor stem cells one could state that the brain, barring any disease, was able to repair itself and maintain its capability to learn far into the twilight years.
Now a new discovery that looks at the regulation of genes associated with neurons in the brain sends us plummeting once more and raises new issues about cognitive competence - after the age of 40.
As per the CNN article Brain genes start to slow at 40 , (or for those with a full subscription to Nature see Gene regulation and DNA damage in the ageing human brain for the original research article) it has been shown that after the age of 40 a number of important cognitive function related genes start to malfunction.
Considering all of the other waning physiological functioning that occurs at or before this age, it should come as no surprise that cognitive performance is also affected. The diminishing returns on investment of exercise and dietary moderation are all too apparent as we get older, yet mental impairment is something we prefer not to, pardon the pun, think about. Yet as the above research so compellingly makes obvious it is something which is very real.
For those interested in the science of how this discovery was made, DNA microarray analysis methods were used to monitor the activity of approximately 460 age regulated genes in a group of 30 people with an age span from 26 to 104 years. It was found that after the age of 40, a number of genes associated with neuron function in the brain become down-regulated, in other words they either stopped or slowed down in their capacity to produce the proteins they encode. What is striking about this study is WHY they became down-regulated: accelerated DNA damage. To test if they could stop this DNA damage they cultured neuron cells that showed the same aging effect but inserted into these cells extra copies of a DNA repair gene, OGG1. Astonishingly, the cells with extra OGG1 did not show down-regulation and were able to maintain their pre-40 year old state.
Ok. So now we finally have empirical evidence. Life does not begin at 40. The brain begins to malfunction at 40 - due to ineffective DNA repair. This is scary. However, knowing why it happens provides us with vital clues on a therapeutic strategy. By increasing NER (nucleotide excision repair) function, using modern gene therapy techniques, DNA damage can be substantially reduced and gene regulation does not have to direct the cell to the aging pathway. The problem is that you wont get FDA approval for genetic therapies in seemingly healthy 40 plus year old brains just to maintain cognitive virility. But that's another story.
Back to scary. Not only is it scary for all those over 40 but for those under 40 as well - and not just because their own brain is getting older due to DNA damage. It has become indoctrinated across all cultures since time immemorial that the elderly were wise and thus became leaders or advisers of leaders. The definition of elderly 2000 years ago would be anyone over 35 (you could easily be a grandfather at 32 if your sired your first at 16). It made sense that an individual with a more extensive set of experiences would be more able to survive and be a superior leader than those with lesser experience.
These days however, thanks to some antibiotics and anti-inflammatories, we have pushed the numbers of those whose life-span exceeds 60 quite easily. Bearing in mind that at 40 the damage begins, can you imagine just how much damage has occurred to the brains of most individuals by this age? Its scary. Here's what even more scary. Actually the implications are terrifying. Do you know the age bracket of most individuals in positions of senior responsibility? Im talking about judges, senior medical doctors, politicians, etc... Do you know the average age of the supreme court justices? Would you like a biopsy of their brain so we can run a gene activity analysis? I sure would.
We are talking about competence, judgment and reasoning capacity. These are people that directly or indirectly will one day if they have not already, influence our lives. I'm not talking having your grandmother's sweet words of wisdom here. I'm talking about decisions being made everyday that require precision, competent analysis of all available information and objective consideration. These are being made by people with age-related, undiagnosed, and I will not mince words, age related brain damage!
Before you start laughing, have a think about it. If you wanted to hire someone to run as fast as possible you would not choose a 70 year old. So if you wanted to hire someone to think as sharply as possible you would not choose a 70 year old either.
To those over 40 out there... We will not always need to use a procedure as invasive as taking a biopsy to measure your neural gene regulation activity. The technology is already available to measure mRNA levels from a blood sample. Soon we should be able to measure neural genetic damage indirectly, say using methylation patterns in other cells derived from saliva, or from the DNA of hair or nail clippings. And I'm not kidding.
So, most venerable gentlemen... If you wish to keep your lofty positions in a near future of complete genetic regulation exclosure, it would be prudent to look at the benefits of NER, particularly OGG1.
How old is Rummy again?
Harold Brenner (prometheus)
Athens, Greece
Edited by prometheus, 21 June 2004 - 11:21 AM.