RE: specific amino acid restriction does the same thing as calorie restriction?

From: Rafal Smigrodzki (rafal@smigrodzki.org)
Date: Mon Apr 21 2003 - 17:17:23 MDT

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    owner-extropians@extropy.org wrote:
    > Subject: Re: specific amino acid restriction does the same thing as
    > calorie restriction?
    >
    >
    >
    > Robert Bradbury wrote:
    >
    >> The working hypothesis that others (and I) have had is that if
    >> you increase protein recycling one gets a greater ratio of
    >> "new" proteins vs. "old" proteins. The new proteins are less
    >> damaged than the old proteins (from say oxidative or deamidation
    >> damage) and thus function more reliably/efficiently. An increase
    >> in the protein turnover rate may also cause proteins to be broken
    >> down before they accumulate sufficient damage that the normal
    >> recycling mechanisms will not work and they end up accumulating
    >> as lipofuscin.
    >
    > Yes. However, as with all aspects of aging, the best solution is
    > not to slow down the progression of the problem (by methods such as
    > stimulating protein recycling), but to *reverse* that progression.
    > In this case, our best bet is to find bacterial or fungal enzymes
    > that can break down lipofuscin and introduce them transgenically
    > with modifications to target them to lysosomes. The same approach
    > can be used to treat atherosclerosis, neurodegenerative diseases,
    > and macular degeneration -- all of these are caused by aggregates
    > of stuff that the lysosome lacks the enzymatic machinery to degrade.

    ### Do you think that protein aggregation is causative in sporadic AD or PD,
    or that it is involved in the pathomechanism at some later stage, perhaps
    amplifying the damage caused by other factors? Recently it turned out that
    APP has a direct toxic effect on mitochondria, and mutant alpha-synuclein
    has also been implicated in diminished mito function.

    Also, are protein aggregates in AD and PD really lysosomal, or cytoplasmic
    (or even extracellular)?

    Atheromas are not aggregates of lysosomally indigestible material, so
    improving cellular digestion is not likely to be of help.

    Is there any indication that lipofuscin is indeed causally involved in cell
    death?

    BTW, I agree that the best way of fighting aging is reversing it by genetic
    engineering (once you get it to work). I like your idea of transferring
    mtDNA-encoded function to the nucleus. Any more information on this project?

    Rafal



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