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Phenoptosis by glycocorticoid dysregulation

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#1 olaf.larsson

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Posted 11 May 2005 - 02:18 PM

I have an idea that selegine extends life by extending neuronal lifespan in hypocampus and thus delaying glycocorticoid dysregulation onset by age. The process is following:

1. the hypothalamus releases corticotropin-releasing hormone (CRH)

2. CRH stimulates the release of ACTH from the anterior pituitary

3. ACTH causes the release of glycocorticoids from the adrenal cortex


*supress immunsystem
*Increase catabolism of protein
*Supress libido
*Supress tissuerepair ability
*Increase blood glucose
*Decrese growth
*Could injure and kill nervcells
+many decrimental effects

Levels of glycocorticoids are higher in old people and animals probebly due to dysregulation of the loop by neuronal death in hypocampus. The process is controlled by an autoregulatory loop. High levels of glycocorticoids could kill the neurons in hypothalamus regulating the levels of glycocorticoids themselves thus leading to even more dysregulation. Selegine protects neurons from death by an unknown process extending life of rats by up to 20%. I suspect the protection of hypothalamic neurons could be important since the neurons there seem control so many functions associated to aging.

The phenoptosis which happen to salomons after mating is due to total glycocorticoid dysregulation. If aging is to at least some extent similar to this phenoptosis it opens up for pharmacological interventions in the process.

Edited by wolfram, 12 May 2005 - 12:08 PM.


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Posted 15 May 2005 - 03:58 AM

Sounds interesting Wolfram. Can you provide some references for how the salmon rapid onset of senescence (as you call it phenoptosis) is brought about by glucocorticoid dysregulation - or this an assumptive part of your hypothesis of selegiline neuroprotection?

You may find the following (1) of interest as regards to neuroprotective mechanisms of a related compound.

(1) Brain Res Brain Res Rev. 2005 Apr;48(2):379-87.
Mechanism of neuroprotective action of the anti-Parkinson drug rasagiline and its derivatives.
Mandel S, Weinreb O, Amit T, Youdim MB.

#3 kevin

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Posted 15 May 2005 - 07:07 AM

Link: http://www.ncbi.nlm....t_uids=11976198

Here we see a perspective that if we consider ourselves as analgous to cells, death is a way of removing the old and damaged. Sound familiar? Is a community a living organism, subject to evolution and natural selection? [sfty]

Ann N Y Acad Sci. 2002 Apr;959:214-37. Related Articles, Links

Programmed death phenomena: from organelle to organism.
Skulachev VP.

Department of Bioenergetics, A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119899, Russia. skulach@genebee.msu.su

Programmed death phenomena appear to be inherent not only in living cells (apoptosis), but also in subcellular organelles (e.g., self-elimination of mitochondria, called mitoptosis), organs (organoptosis), and even whole organisms (phenoptosis). In all these cases, the "Samurai law of biology"--it is better to die than to be wrong--seems to be operative. The operation of this law helps complicated living systems avoid the risk of ruin when a system of lower hierarchic position makes a significant mistake. Thus, mitoptosis purifies a cell from damaged and hence unwanted mitochondria; apoptosis purifies a tissue from unwanted cells; and phenoptosis purifies a community from unwanted individuals. Defense against reactive oxygen species (ROS) is probably one of the primary evolutionary functions of programmed death mechanisms. So far, it seems that ROS play a key role in the mito-, apo-, organo-, and phenoptoses, which is consistent with Harman's theory of aging. Here a concept is described that tries to unite Weismann's hypothesis of aging as an adaptive programmed death mechanism and the generally accepted alternative point of view that considers aging as an inevitable result of accumulation in an organism of occasional injuries. It is suggested that injury accumulation is monitored by a system(s) actuating a phenoptotic death program when the number of injuries reaches some critical level. The system(s) in question are organized in such a way that the lethal case appears to be a result of phenoptosis long before the occasional injuries make impossible the functioning of the organism. It is stressed that for humans these cruel regulations look like an atavism that, if overcome, might dramatically prolong the human life span.

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#4 olaf.larsson

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Posted 16 May 2005 - 05:52 PM

Can you provide some references for how the salmon rapid onset of senescence (as you call it phenoptosis) is brought about by glucocorticoid "dysregulation".

The salomons dont die becouse of dysregulation rather by total blockage of regulation which makes glycocorticoidlevels rocket sky high. If adrenal cortex of this salomons is removed they live much longer without any problems.

The claim that phenoptosis in salomons is started by blockage of regulation is made in a book called "Why Zebras Don't Get Ulcers" by Robert M.Sapolsky professor at Stanford University California. Sapolsky also claimes that glycocorticoids have varios decrimental proaging effects on the body, and that the glycocorticoid system becomes dysregulated with age due to neuron loss in hypocampus.

Sapolsky doesn´t claim that Selegine is preventing aging by protecting neurons in hypocampus. Since I happen to know Selegine, this is a conclusion i have drawn myself, while reading Sapolsky´s very interessting book.


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Posted 16 May 2005 - 10:50 PM

Thanks wolfram, I'll look into this further.

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