As far as I know, this is a confirmed first. Lipofuscin safely removed from cells. Could be very significant.
Posted 12 February 2012 - 05:52 AM
Neurobiol Aging. 2012 Jan 12. [Epub ahead of print]
Lipofuscin can be eliminated from the retinal pigment epithelium of monkeys.
Julien S, Schraermeyer U.
SourceSection of Experimental Vitreoretinal Surgery, Centre for
Ophthalmology, Tübingen, Germany.
Lipofuscin is a cytologic hallmark of aging in metabolically active postmitotic cells including neurons, cardiac muscle cells, and the retinal pigment epithelium (RPE). High levels of lipofuscin are involved in the pathogenesis of age-related macular degeneration (AMD), the main cause of blindness in the elderly population in the western world. Degradation and exocytosis of lipofuscin by RPE cells have not been observed in vivo until now, and no drug is known to eliminate the intracellular amount of lipofuscin. Here, we show that in monkeys treated with a small molecule belonging to the tetrahydropyridoethers class (n = 36 of 48 monkeys), RPE cells significantly release lipofuscin. In 4 eyes, macrophages were detected which had taken up lipofuscin. They were located between the Bruch's membrane and the RPE, and in the choroid. The quantification of pigment granules was performed by transmission electron microscopy. Our findings open the way to develop therapeutic strategies to remove lipofuscin from RPE cells, which may have implications for the treatment of age-related macular degeneration in which lipofuscin accumulation in cells is a causative factor.
Edited by Michael, 08 May 2012 - 07:58 PM.
Posted 12 February 2012 - 02:26 PM
Posted 12 February 2012 - 02:26 PM
Tetrahydropyridoethers Eliminate Lipofuscin From Retinal Pigment Epithelium of Monkeys
<nobr>U. Schraermeyer</nobr>, <nobr>S. Schultheiss</nobr>, <nobr>S. Hofmeister</nobr> and <nobr>S. Julien</nobr>
Experimental Vitreoretinal Surgery, Institute for Ophthalmic Research, Tubingen, Germany
Commercial Relationships: U. Schraermeyer, None; S. Schultheiss, None; S. Hofmeister, None; S. Julien, None.
Purpose:To test the effect of tetrahydropyridoethers (THPE) on pigment granules of the retinal pigment epithelium (RPE), monkeys (Macaca fascicularis) were orally treated with this drug for up to one year.
Methods:54 monkeys were daily treated with different concentrations of (7R, 8R, 9R)-2,3-dimethyl-8-hydroxy-7-(2-methoxyethoxy)-9-phenyl-7,8,9,10-tetrahydro-imi-dazo [1,2-h] [1,7] naphthyridine between 4 weeks and one year by oral administration. 12 monkeys served as controls. Right eyes were investigated by electron microscopy, left eyes were used for immunocytochemistry and fluorescence light microscopy.
Results:After exposure to THPE, focal depigmentation of RPE cells was observed. These sites were about 100 - 1000 µm long and their numbers were dose-dependent. Lipofuscin granules, melanosomes as well as melanolipofuscin granules disintegrated within the RPE cells and/or were released to macrophages. Different stages of pigment lysis were detected under the electron microscope. There were areas of 1000 µm2 or more in which the RPE was completely free of melanin and lipofuscin granules. Close to such depigmented RPE cells, highly pigmented macrophages identified by CD68 staining were located between Bruch’s membrane and the RPE and in the subretinal space or within the choroid.The total number of lipofuscin granules was counted in the cytoplasm of RPE cells from untreated and treated monkeys. Per 10 µm of RPE length, 7.2 ± 3.6 versus 0.07 ± 0.26 lipofuscin granules were found in RPE cells of untreated versus treated animals respectively ( p = 9,9E-08). Photoreceptors facing depigmented RPE appeared normal.
Conclusion: Our results demonstrate that administration of THPE induces lipofuscin elimination from RPE cells in a dose-dependent manner by degradation in RPE cells and/or transfer to macrophages. Although the mechanism is still unknown, this is an important finding which disproves the dogma of undegradable and unremovable lipofuscin from RPE cells and has the potential to serve as an active ingredient in the treatment of AMD, particularly the dry form.
Edited by okok, 12 February 2012 - 03:09 PM.
Posted 12 February 2012 - 03:56 PM
Cytoprotective. Used in the treatment of ulcers.
Posted 12 February 2012 - 07:23 PM
Posted 12 February 2012 - 08:47 PM
Posted 12 February 2012 - 10:54 PM
Posted 12 February 2012 - 11:04 PM
Posted 12 February 2012 - 11:05 PM
At some point, if we can get rid of all this various age-related cellular gunk, how does an old cell differ from a young one? Indeed, how could we even tell which was which? Does aging stop then?
Posted 13 February 2012 - 12:22 AM
Posted 13 February 2012 - 02:08 PM
In their excellent properties, the compounds according to the invention surprisingly prove to be clearly superior to the compounds known from the prior art in various models in which the antiulcerogenic and the antisecretory properties are determined. On account of these properties, the compounds of the formula and their pharmacologically tolerable salts are outstandingly suitable for use in human and veterinary medicine, where they are used, in particular, for the treatment and/or prophylaxis of disorders of the stomach and/or intestine.
Posted 13 February 2012 - 11:35 PM
To summarize the article, lipofuscin as recently discovered is mainly composed of oxidized lipid fragments and bisretinoids.
Remofuscin probably works by exocytosis and subsequent macrophage clearance.
Recently, several small molecules have been shown to decrease the new formation of bisretinoid lipofuscin. Horseradish peroxidase also degrades it.
This would make for an interesting future podcast episode. Mind?
Posted 13 February 2012 - 11:41 PM
Posted 14 February 2012 - 12:00 AM
Nice to know, but the real "killer app" is getting rid of it.
Creatine inhibits lipofuscin accumulation in mice:
Posted 14 February 2012 - 01:16 AM
Posted 19 February 2012 - 02:29 AM
Well, the lipofuscin and the "cellular gunk" are not all of the changes, that happen with the cells during aging. If not anything else tt least DNA damage accumulates too. Moreover, some scientists suggest, that the damage of the DNA and the corresponding with it "wrong proteins" is a main factor for the accumulation of "all the cellular gunk", and they suppose, that even after the removal of the "gunc", it will accumulate again if the DNA remains damaged. So, the aged and the young cell will still have differences.
3. The drug is taken up by the lysosome and directly dissolves the lipofuscin. This would be the easiest to test. Put lipofuscin in a dish. Add the tetrahydropyridoethers drug. See what happens. Since the drug is over 30 years old, patent protection should have run out, correct?
Edited by steampoweredgod, 19 February 2012 - 02:33 AM.
Posted 19 February 2012 - 06:32 AM
Posted 19 February 2012 - 03:31 PM
Another possibility is to cause the lysosome to merge with the external membrane and thus expel all material within it to the extracellular environment. It may be a function that lies dormant in this cell type but other cells may use. Neurons presumably given their high metabolic activity(even while not sending messages) and century plus lifespan may be doing this, but maybe not at a sufficient rate to halt accumulation.
Edited by Mind, 19 February 2012 - 03:31 PM.
Posted 19 February 2012 - 07:50 PM
Edited by steampoweredgod, 19 February 2012 - 08:31 PM.
Posted 22 February 2012 - 12:35 AM
Posted 23 February 2012 - 10:22 PM
Posted 01 April 2012 - 12:08 AM
Posted 06 May 2012 - 07:54 PM
Posted 06 May 2012 - 09:06 PM
Posted 07 May 2012 - 02:06 AM
Wow, yes, but how can we move this research forward? I sent an email to the UKT but no response. Anyone out there willing to get some lipofuscin and the chemical and do some tests?
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