[因為發現如何在實驗室內研究記憶，而得到 2000年諾貝爾獎的
Eric Kandel 又一重要的發現， “不像
Alzheimer's 病人腦內記憶細胞喪失，一般老人記憶細胞並沒消失，因此可能用蛋白質 PbAp48恢復老人的記憶力”。Kandel 現在 84歲，他的傳記在筆者的 “微生物學史”(合記出版社)，長達一頁。他如何發現在實驗室內用鼻涕蟲Aplysia研究記憶，很有趣、很有趣!!]
Eric Kandel 又一重要的發現， “不像
Alzheimer's 病人腦內記憶細胞喪失，一般老人記憶細胞並沒消失，因此可能用蛋白質 PbAp48恢復老人的記憶力”。Kandel 現在 84歲，他的傳記在筆者的 “微生物學史”(合記出版社)，長達一頁。他如何發現在實驗室內用鼻涕蟲Aplysia研究記憶，很有趣、很有趣!!]
Scientists discover key to normal memory lapses in
seniors
seniors
Sharon Begley 20 hours ago
By Sharon Begley
NEW YORK (Reuters) - Scientists have
good news for all the older adults who occasionally forget why they walked into
a room - and panic that they are getting Alzheimer's disease.
good news for all the older adults who occasionally forget why they walked into
a room - and panic that they are getting Alzheimer's disease.
Not only is age-related memory loss
a syndrome in its own right and completely unrelated to that dread disease, but
unlike Alzheimer's it may be reversible or even preventable, researchers led by
a Nobel laureate said in a study published on Wednesday.
a syndrome in its own right and completely unrelated to that dread disease, but
unlike Alzheimer's it may be reversible or even preventable, researchers led by
a Nobel laureate said in a study published on Wednesday.
Using human brains that had been
donated to science as well as the brains of lab mice, the study for the first
time pinpointed the molecular defects that cause cognitive aging.
donated to science as well as the brains of lab mice, the study for the first
time pinpointed the molecular defects that cause cognitive aging.
In an unusual ray of hope for a
field that has had almost nothing to offer older adults whose memory is
failing, the study's authors conclude that drugs, foods or even behaviors might
be identified that affect those molecular mechanisms, helping to restore
memory.
field that has had almost nothing to offer older adults whose memory is
failing, the study's authors conclude that drugs, foods or even behaviors might
be identified that affect those molecular mechanisms, helping to restore
memory.
Any such interventions would
represent a significant advance over the paltry offerings science has come up
with so far to prevent memory decline, such as advice to keep cognitively
active and healthy - which helps some people, but not all, and has only a
flimsy scientific foundation. By identifying the "where did I park the
car?" molecule, the discovery could also kick-start the mostly moribund
efforts to develop drugs to slow or roll back the memory lapses that accompany
normal aging.
represent a significant advance over the paltry offerings science has come up
with so far to prevent memory decline, such as advice to keep cognitively
active and healthy - which helps some people, but not all, and has only a
flimsy scientific foundation. By identifying the "where did I park the
car?" molecule, the discovery could also kick-start the mostly moribund
efforts to develop drugs to slow or roll back the memory lapses that accompany
normal aging.
"This is a lovely set of
studies," said Molly Wagster of the National Institute on Aging, an expert
on normal age-related memory decline who was not involved in the new study.
"They provide clues to the underlying mechanism of age-related memory
decline and will, hopefully, move us down the road toward targeted
therapeutics."
studies," said Molly Wagster of the National Institute on Aging, an expert
on normal age-related memory decline who was not involved in the new study.
"They provide clues to the underlying mechanism of age-related memory
decline and will, hopefully, move us down the road toward targeted
therapeutics."
About 40 percent of Americans age 85
and older say they experience some memory loss, a 2009 survey by the Pew
Research Center found, as did 27 percent of those 75 to 84 and 20 percent of
those ages 65 to 74.
and older say they experience some memory loss, a 2009 survey by the Pew
Research Center found, as did 27 percent of those 75 to 84 and 20 percent of
those ages 65 to 74.
BRAIN BANK
The researchers began with eight
brains from the New York Brain Bank at Columbia University donated by people
aged 33 to 88 who were free of brain disease when they died. They extracted
two structures in the hippocampus, a vital cog in the brain's memory machinery:
the dentate gyrus, a
boomerang-shaped region whose function declines with age but is not affected by
Alzheimer's, and the entorhinal
cortex, which is largely unaffected by aging but is where Alzheimer's
first takes hold, killing neurons.
brains from the New York Brain Bank at Columbia University donated by people
aged 33 to 88 who were free of brain disease when they died. They extracted
two structures in the hippocampus, a vital cog in the brain's memory machinery:
the dentate gyrus, a
boomerang-shaped region whose function declines with age but is not affected by
Alzheimer's, and the entorhinal
cortex, which is largely unaffected by aging but is where Alzheimer's
first takes hold, killing neurons.
The scientists then measured which
genes had been active in each structure, and found one suspicious difference:
17 genes in the dentate gyrus became more active, or less, as the age of the
brain increased.
genes had been active in each structure, and found one suspicious difference:
17 genes in the dentate gyrus became more active, or less, as the age of the
brain increased.
The most significant change was that
the gene for a protein called RbAp48 had essentially retired: The
gene's activity tailed off dramatically the older a brain got. As a result,
old brains had about half the RbAp48 of young brains, the scientists report
online in the journal Science Translational Medicine.
the gene for a protein called RbAp48 had essentially retired: The
gene's activity tailed off dramatically the older a brain got. As a result,
old brains had about half the RbAp48 of young brains, the scientists report
online in the journal Science Translational Medicine.
The scientists then sampled 10 more
healthy human brains, ranging from 41 to 89 years at the time of death. Once
again, the amount of RbAp48 protein declined with age in the dentate gyrus. They
next confirmed that RbAp48 protein was also less abundant in the dentate gyrus
of old mice compared to young ones.
healthy human brains, ranging from 41 to 89 years at the time of death. Once
again, the amount of RbAp48 protein declined with age in the dentate gyrus. They
next confirmed that RbAp48 protein was also less abundant in the dentate gyrus
of old mice compared to young ones.
For the final step, the scientists
had to nail down whether the missing protein caused age-related memory loss.
They genetically engineered mice whose RbAp48 genes were disabled. Result: The
young mice had memories as poor as animals four times their age (the mouse
equivalent of late middle age), and they had terrible trouble navigating a water
maze or differentiating objects they had seen before from novel ones.
had to nail down whether the missing protein caused age-related memory loss.
They genetically engineered mice whose RbAp48 genes were disabled. Result: The
young mice had memories as poor as animals four times their age (the mouse
equivalent of late middle age), and they had terrible trouble navigating a water
maze or differentiating objects they had seen before from novel ones.
Crucially, the scientists also did
the reverse experiment, engineering mice so their brains had extra doses of
RbAp48. The mice's memories returned to the flower of youth.
the reverse experiment, engineering mice so their brains had extra doses of
RbAp48. The mice's memories returned to the flower of youth.
"With RbAp48, we were able
to reverse age-related memory loss in the mice," said Columbia's Dr
Eric Kandel, who shared the 2000 Nobel Prize in medicine for discoveries of the
molecular basis of memory and led the research. "Unlike in Alzheimer's,
there is no significant cell death in age-related memory loss, which gives us
hope it can be prevented or reversed."
to reverse age-related memory loss in the mice," said Columbia's Dr
Eric Kandel, who shared the 2000 Nobel Prize in medicine for discoveries of the
molecular basis of memory and led the research. "Unlike in Alzheimer's,
there is no significant cell death in age-related memory loss, which gives us
hope it can be prevented or reversed."
Exactly how RbAp48 does that is not
clear. The protein acts as a sort of genetic master key: By causing chromosomes
to loosen their hold on the molecular spool they are wound around like thread,
it allows genes to be turned on. Among the activated genes, Kandel explained,
are those involved in forming memories.
clear. The protein acts as a sort of genetic master key: By causing chromosomes
to loosen their hold on the molecular spool they are wound around like thread,
it allows genes to be turned on. Among the activated genes, Kandel explained,
are those involved in forming memories.
The emerging picture is that levels
of RbAp48 decline with age, allowing chromosomes to maintain a death grip
on their spools. Memory genes remain dormant, and you can't remember
that you promised your spouse you would make dinner.
of RbAp48 decline with age, allowing chromosomes to maintain a death grip
on their spools. Memory genes remain dormant, and you can't remember
that you promised your spouse you would make dinner.
The researchers plan to see what
social and dietary factors might boost RbAp48 in mice, said Kandel, who will be
84 in November. Pharmaceuticals, nutraceuticals, physical and cognitive
exercise are all candidates, said Columbia's Dr Scott Small, co-senior author
of the study.
social and dietary factors might boost RbAp48 in mice, said Kandel, who will be
84 in November. Pharmaceuticals, nutraceuticals, physical and cognitive
exercise are all candidates, said Columbia's Dr Scott Small, co-senior author
of the study.
Testing such interventions in mice
should be more useful to humans than tests of drugs for Alzheimer's, he said.
RbAp48 "is different," Small said. "Alzheimer's does not occur
naturally in the mouse. Here, we've caused age-related memory loss in the
mouse, and we've shown it to be relevant to human aging."
should be more useful to humans than tests of drugs for Alzheimer's, he said.
RbAp48 "is different," Small said. "Alzheimer's does not occur
naturally in the mouse. Here, we've caused age-related memory loss in the
mouse, and we've shown it to be relevant to human aging."
(Reporting by Sharon Begley; Editing
by Julie Steenhuysen and Prudence Crowther)
by Julie Steenhuysen and Prudence Crowther)
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