Posted 09 March 2009 - 03:39 AM
According to Aubrey's book, centrophenoxine doesn't work either. It seems that people were mistakenly calling ceroid lipofuscin. Here are some of what he cites.
Ann N Y Acad Sci. 2002 Apr;959:57-65.
Pigments in aging: an overview.
Department of Pathology, University of Hawaii, School of Medicine, Honolulu, Hawaii 96822, USA. email@example.com
Although during the normal aging process there are numerous pigmentary changes, the best recognized are those of melanin and lipofuscin. Melanin may increase (e.g., age spots, senile lentigo, or melanosis coli) or decrease (e.g., graying of hair or ocular melanin) with age, while lipofuscin (also called age pigment) always increases with age. In fact, the time-dependent accumulation of lipofuscin in lysosomes of postmitotic cells and some stable cells is the most consistent and phylogenetically constant morphologic change of aging. This pigment displays a typical autofluorescence (Ex: approximately 440; Em: approximately 600 nm), sudanophilia, argyrophilia, PAS positiveness, and acid fastness. Advances on its biogenesis, composition, evolution, and lysosomal degradation have been hampered by the persistent confusion between lipofuscin and the large family of ceroid pigments found in a variety of pathological conditions, as evidenced by the frequent use of the hybrid term lipofuscin/ceroid by investigators mainly working with in vitro systems of disputable relevance to in vivo lipofuscinogenesis. While lipofuscin and ceroid pigments may share some of their physicochemical properties at one moment or another in their evolutions, these pigments have different tissue distribution, rates of accumulation, origin of their precursors, and lectin binding affinities. Although it is widely believed that lipofuscin is a marker of oxidative stress, and that it can be, therefore, modified by antioxidants and prooxidants, these assumptions are mainly based on in vitro experiments and are not generally supported by in vivo studies. Another common misconception is the belief that lipofuscin can be extracted from tissues by lipid solvents and measured spectrofluorometrically. These and other disturbing problems are reviewed and discussed in this presentation.
Exp Gerontol. 1985;20(6):333-40.
Quantitative studies of the effects of aging, meclofenoxate, and dihydroergotoxine on intraneuronal lipopigment accumulation in the rat.
Intraneuronal lipopigment accumulation is associated with ageing and certain diseases, and there are many claims that this can be influenced by drugs, particularly meclofenoxate (centrophenoxine). The various unsubstantiated or conflicting reports of the effects of this drug in animal studies indicate the need for methods for the demonstration of lipopigment accumulation in adequately defined, easily-identified, and relatively homogeneous neuronal populations; this study has validated two such methods by demonstrating significant differences between groups of rats at different ages in respect of measured lipopigment autofluorescence intensity from the most heavily pigmented regions of a subpopulation of Purkinje cells, and of the area overlying intraneuronal lipopigment in a region of the hippocampus. These methods were then used to investigate the effects of daily (5 days per week) intraperitoneal injections of meclofenoxate or dihydroergotoxine, over a period of 12 weeks, before sacrifice at 13.5 months. No significant effects of meclofenoxate were detected, but dihydroergotoxine administration was associated with a significant increase in mean area overlying intraneuronal lipopigment in the CA3a region of the hippocampus. The results do not confirm that meclofenoxate can induce a reduction in intraneuronal lipopigment, but suggest that chronic dihydroergotoxine administration was associated with an increase in intraneuronal volume of lipopigment in the cell bodies of CA3a hippocampal neurones.
Neurobiol Aging. 1986 Mar-Apr;7(2):107-13.
Lipofuscin in retinal pigment epithelium of rhesus monkey: lack of diminution with centrophenoxine treatment.
Andrews LD, Brizzee KR.
An experiment was performed to test the ability of Centrophenoxine to reduce the amount of lipofuscin (age pigment) in the retinal pigment epithelium (RPE) of aged rhesus monkeys. Centrophenoxine is reputed to have this action in neurons of lower mammals. Quantitative electron microscopic analysis was performed on sections from the perifovea of ten rhesus monkeys, all approximately 20 years of age. Four of the animals received 80 mg/kg Centrophenoxine (IM injection) daily for 12 weeks. No significant difference between the treated and control groups could be demonstrated statistically (Mann-Whitney U-test) either in the fraction of RPE cell cytoplasm occupied by lipofuscin granules or in the average size of the granules.
J Gerontol. 1983 Sep;38(5):525-31.
Lipofuscin response to the "aging-reversal" drug centrophenoxine in rat retinal pigment epithelium and frontal cortex.
Katz ML, Robison WG Jr.
The effects of centrophenoxine on the lipofuscin contents of the retinal pigment epithelium (RPE) and frontal cortex of the brain were examined in senescent female Fischer rats. Rats (106 weeks old) were injected daily for 11 weeks with centrophenoxine (80 to 120 mg/kg body weight) or saline, and then sacrificed along with untreated 28- and 46-week-old controls. The number of lipofuscin granules seen in the RPE by light microscopy increased by 70% between 28 and 117 weeks of age in control animals. There was a concomitant age-related increase in lipofuscin specific fluorescence in the RPE. Centrophenoxine treatment neither reduced the amount of lipofuscin, nor altered the ultrastructural appearance of lipofuscin granules in the RPE. Between 28 and 117 weeks of age, there was an almost nine-fold increase in the lipofuscin content of the frontal cortex of control animals; centrophenoxine treatment failed to reverse this pigment accumulation.