The idea that Parkinson's Disease (PD) is an accelerated form of brain aging has been around for quite a long time. However, as with aging more generally any hypothesis as to the mechanisms behind Parkinson's needs to explain all the known research data.
I have been discussing PD with a number of people over the past few months. The results from research indicate that Parkinsons is not primarily caused by genetic factors. That is because there are studies where individual twins get Parkinsons, whilst their twin does not. I was wondering, therefore, what might be an alternative cause.
This paper is one that substantiates the argument that normally the brain does not age as fast as the rest of the body.
What we need to look at is what might cause this to happen. If we start with the assumption from my previous posts that aging results from the mutation of mitochondrial DNA (mtDNA) then we need to find something that prevents the mutation of mtDNA in the brain that does not operate elsewhere. That is easy to find. It is the existance of Cerebro Spinal Fluid CSF. When people go to sleep the blood pressure goes down and CSF becomes more available to the brain. Within CSF there is a high concentration of melatonin and melatonin protects mtDNA from damage. The pineal gland generates melatonin as part of the daily circadian cycle and injects some of that directly into the CSF. Hence we know why the brain is more protected from mtDNA damage (aging) than the rest of the body. The question then is why people with PD find that their brain is less protected.
It is also quite clear that there is evidence that the level of melatonin in the third ventricle of people with PD is lower than people who don't have PD.
The table below is from this article Significance of High Levels of Endogenous Melatonin in Mammalian Cerebrospinal Fluid and in the Central Nervous System
What is not immediately obvious from this table is that the last line (Leston et Al) is from Patients with PD. It demonstrates a much lower level of melatonin in the third ventricle.
There are two possible causes for this:
a) A higher proportion goes into serum than in non-PD patients
b) Less melatonin is generated.
It does not immediately matter although in rectifying this may lie part of the solution to PD. What matters is that brain cells are getting less melatonin than in non-PD people. Hence their mitochondrial DNA has less protection. This to me seems to be the cause of the accelerated brain aging that is seen with PD.
nb the penultimate line is Traumatic Brain Injury.
I have been discussing PD with a number of people over the past few months. The results from research indicate that Parkinsons is not primarily caused by genetic factors. That is because there are studies where individual twins get Parkinsons, whilst their twin does not. I was wondering, therefore, what might be an alternative cause.
This paper is one that substantiates the argument that normally the brain does not age as fast as the rest of the body.
What we need to look at is what might cause this to happen. If we start with the assumption from my previous posts that aging results from the mutation of mitochondrial DNA (mtDNA) then we need to find something that prevents the mutation of mtDNA in the brain that does not operate elsewhere. That is easy to find. It is the existance of Cerebro Spinal Fluid CSF. When people go to sleep the blood pressure goes down and CSF becomes more available to the brain. Within CSF there is a high concentration of melatonin and melatonin protects mtDNA from damage. The pineal gland generates melatonin as part of the daily circadian cycle and injects some of that directly into the CSF. Hence we know why the brain is more protected from mtDNA damage (aging) than the rest of the body. The question then is why people with PD find that their brain is less protected.
It is also quite clear that there is evidence that the level of melatonin in the third ventricle of people with PD is lower than people who don't have PD.
The table below is from this article Significance of High Levels of Endogenous Melatonin in Mammalian Cerebrospinal Fluid and in the Central Nervous System
Summary of the Presumed Physiological Concentrations of Melatonin in Human CSF
| Reference | Year | Melatonin (pg/ml) | |||||
|---|---|---|---|---|---|---|---|
| Collection Time | Collection Site | Ages (Yr) | Method | Melatonin Form | |||
| Rousseau et al. [54] | 1999 | 08:00-09:00h | Lumbar cistern | 25.3 ± 4.5 | RIA | Free | 32.5 ± 25.5 |
| Rousseau et al. [54] | 1999 | 08:00-09:00h | Lumbar cistern | 25.3 ± 4.5 | RIA | Free | 32.5 ± 25.5 |
| Rousseau et al. [54] | 1999 | 08:00-09:00h | Lumbar cistern | 25.3 ± 4.5 | RIA | Free | 32.5 ± 25.5 |
| Liu et al.[31] | 1999 | 1-12 h after death | Ventricular | 76 ± 1.4 | RIA | Free | 273 ± 47 |
| Rizzo et al. [53] | 2002 | Night | Lumbar cistern | N/A | HPLC | Free + bound | 28.6 ± 7.0 |
| Rizzo et al. [53] | 2002 | Night | Lumbar cistern | N/A | HPLC | Free + bound | 28.6 ± 7.0 |
| Zhou et al. [72] | 2003 | 1-12 h after death | Ventricule | 76 ± 2 | RIA | Free | 280 ± 64 |
| Longatti et al.[34] | 2004 | Day time | Third ventricule | N/A | N/A | Free | 542 |
| Longatti et al. [35] | 2007 | Day time | Third ventricule | 60.3 ± 17.9 | HPLC | Free + bound | 442 ± 45 |
| Seifman et al. [34] | 2008 | 09:00h | ventricule | 30-74 | ELISA | Free | 1.47 ± 0.35 |
| Leston et al.[30] | 2010 | 08:10-11:10 h | Third ventricule | 26-68 | RIA | Free | 8.69 ± 2.75 |
What is not immediately obvious from this table is that the last line (Leston et Al) is from Patients with PD. It demonstrates a much lower level of melatonin in the third ventricle.
There are two possible causes for this:
a) A higher proportion goes into serum than in non-PD patients
b) Less melatonin is generated.
It does not immediately matter although in rectifying this may lie part of the solution to PD. What matters is that brain cells are getting less melatonin than in non-PD people. Hence their mitochondrial DNA has less protection. This to me seems to be the cause of the accelerated brain aging that is seen with PD.
nb the penultimate line is Traumatic Brain Injury.
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