X-Message-Number: 25680
Date: Sat, 12 Feb 2005 22:02:25 -0800 (PST)
From: Doug Skrecky <>
Subject: diet containing protease inhibitors

[...is probably not a good diet!]

Arch Gerontol Geriatr. 1991 Mar-Jun;12(2-3):119-31
The protease inhibitor leupeptin induces several signs of aging in brain,
retina and internal organs of young rats.
  The protease inhibitor leupeptin was administered to brain, retina and
internal organs of young rats for up to two weeks in order to determine
if specifically decreased proteolysis could cause symptoms of cellular
aging in a variety of tissues. Electron microscopy showed that leupeptin
induced the formation of dense substances with fine morphologies similar
to and, in many cases, apparently identical with those of natural
lipofuscin from aged tissues. Leupeptin also caused increased
immunoreactivity to ubiquitin in cerebellar Purkinje cells and presumed
Bergmann glia perikarya of brain tissue as well as in hepatocytes of liver
tissue. Both of these effects were found in aged tissues as well.
Finally, both leupeptin treatment and normal aging led to the onset of
immunoreactivity in Purkinje cells to antibodies to the abnormal tau
molecule of paired helical filaments from Alzheimer's disease brain.
Together, these results indicate that inhibition of thiol (and possibly
some serine) proteases by leupeptin is sufficient to cause obvious
morphological manifestations of aging in several tissues, and are thus
consistent with the hypothesis that lipofuscinogenesis as well as a
build-up of ubiquilinated proteins with age is caused by decreased or
defective proteolysis. These effects are likely secondary to the
mechanism(s) interfering with proteolysis itself.

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