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[Mixter]

Mech Ageing Dev. 1978 Aug;8(2):131-8.Links
    Lipofuscinogenesis in mice early treated with centrophenoxine.
    Nandy K.

    Previous studies in our and other laboratories indicated that there is a reduction in the neuronal lipofuscin in old rodents after several weeks of treatment with centrophenoxine. The present study investigates whether this chemical can prevent pigment formation if given early in life before the onset of pigmentogenesis. The study shows that the drug did not stop lipofuscin formation in 1 month old mice. But there was a consistent decrease in the pigment in the neurons of cerebral cortex and hippocampus of the treated animals compared to the age-matched controls. The degree of reduction was largely dependent on the duration of the treatment and a significant diminution was noted after treatment for five months or more.

    PMID: 357853 [PubMed - indexed for MEDLINE]

This study (and about 100 others, look at "Related Studies" at pubmed) demonstrates that centrophenoxine has a mechanism to remove lipofuscin. I haven't found any details on the how this mechanism could work, yet, only on effectiveness. Does anyone know? If there are non-enzymatic ways of breaking up this pigment (chemically and/or by gene activating/downregulating substances), it would be very interesting to know how this works, so one could search for analogs.

Centrophenoxine comprises a DMAE part and a "pCPA" part which is very similar to plant auxines. Auxines are known to extensively regulate genes and induce hormonal changes. (ref. Wikipedia) If an epigenetic or second-messenger mechanism could be confirmed in centrophenoxine's (or pCPA's) lipofuscin removal, that would encourage experimenting a lot more with synthetic auxine derivates to activate/amplify 'hidden garbage-cleaning genes'. Perhaps it is already documented in a study I don't know about (which is mainly why I'm asking). If not, experimenting with bioavailable/BBB-crossing pCPA derivatives to experimentally reduce lipofuscin plaque, might be an interesting option to at least confirm the mechanism.

Btw, is there a complete (according to current knowledge) list of the types of aging related and irremovable extra-/intracellular 'garbage'? I know of: AGEs (is there any open list of the AGE subtypes?), pigments (lipofuscin, neuromelanin...), modified proteins (beta amyloid, modified transthyretin...), lipids (5 alpha-OH-6keto-cholesterol).

[John Schloendorn]

Centrophenoxine - I don't know anything about this compound. All I can say is that one "non-catalytic" way in which lipofuscin could get removed in theory is by exocytosis, and then in the blood via cells or hdl to kidney. In particular in Hippocampus I think there's some evidence for it, using other interventions.

AGE subtypes -- see the "update on a puzzle nearing solution" (this is not complete, but a good start)

Other junk - your list is pretty complete in terms of classes of junk, except vitamin-a derived fluorophores in retinal pigment epithelium which might be seen as an extra class (pubmed "A2E").