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Hi All,

How closely is the altered expression of genes affected by CR shown by its

memetics?

The results may impress.

See the not pdf-available abstract of the paper below.

Dhahbi JM, Mote PL, Fahy GM, Spindler SR.

Identification of potential caloric restriction mimetics by microarray

profiling.

Physiol Genomics. 2005 Sep 27; [Epub ahead of print]

PMID: 16189280

To facilitate the development of assays for the discovery of pharmaceuticals

capable

of mimicking the effects of caloric restriction on life- and healthspan (CR

mimetics), we evaluated the effectiveness of glucoregulatory and putative cancer

chemopreventatives in reproducing the hepatic gene-expression profile produced

by

long-term CR (LTCR) using Affymetrix microarrays. We have shown that CR

initiated

late in life begins to extend lifespan, reduce cancer as a cause of death, and

reproduce ~three quarters of the genomic effects of LTCR in 8 weeks (CR8). Eight

weeks of metformin treatment was superior to CR8 at reproducing LTCR-like gene

expression changes, maintaining a superior number of such changes over a broad

range

of statistical stringencies, and producing more gene ontology terms overlapping

those produced by LTCR. Consistent with these results, metformin has been shown

to

reduce cancer incidence in mice and humans. Phenformin, a chemical cousin of

metformin, extends lifespan and reduces tumor incidence in mice. Taken together,

these results indicate that gene-expression biomarkers can be used to identify

promising candidate CR mimetics.

Al Pater, PhD; email: old542000@...

__________________________________

- PC Magazine Editors' Choice 2005

http://mail.

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Hi Al:

Of course we would all be delighted if we could take a supplement

that would have the same effects on lifespan as CR.

But given all the bad things that are being said about what body fat,

just by way of its existence, does to cause all kinds of trouble, one

wonders whether the mimetic would also have to reduce body

fat ............ without restraint of food intake.

That would seem to be a tall order if the -Benedict kind of

analyses of the relationship between food intake a body weight are

meaningful - I.E. that for any level of caloric intake sustained on

average over a long period there is a corresponding equilibrium body

weight AEE (all else equal).

How can we eat as much as we want, take a CR mimetic supplement, and

not have excessive body fat? If there's a way I'd sure like to know

about it.

Rodney.

--- In , Al Pater <old542000@y...>

wrote:

> Hi All,

>

> How closely is the altered expression of genes affected by CR shown

by its memetics?

> The results may impress.

>

> See the not pdf-available abstract of the paper below.

>

> Dhahbi JM, Mote PL, Fahy GM, Spindler SR.

> Identification of potential caloric restriction mimetics by

microarray profiling.

> Physiol Genomics. 2005 Sep 27; [Epub ahead of print]

> PMID: 16189280

>

> To facilitate the development of assays for the discovery of

pharmaceuticals capable

> of mimicking the effects of caloric restriction on life- and

healthspan (CR

> mimetics), we evaluated the effectiveness of glucoregulatory and

putative cancer

> chemopreventatives in reproducing the hepatic gene-expression

profile produced by

> long-term CR (LTCR) using Affymetrix microarrays. We have shown

that CR initiated

> late in life begins to extend lifespan, reduce cancer as a cause of

death, and

> reproduce ~three quarters of the genomic effects of LTCR in 8 weeks

(CR8). Eight

> weeks of metformin treatment was superior to CR8 at reproducing

LTCR-like gene

> expression changes, maintaining a superior number of such changes

over a broad range

> of statistical stringencies, and producing more gene ontology terms

overlapping

> those produced by LTCR. Consistent with these results, metformin

has been shown to

> reduce cancer incidence in mice and humans. Phenformin, a chemical

cousin of

> metformin, extends lifespan and reduces tumor incidence in mice.

Taken together,

> these results indicate that gene-expression biomarkers can be used

to identify

> promising candidate CR mimetics.

>

> Al Pater, PhD; email: old542000@y...

>

>

>

> __________________________________

> - PC Magazine Editors' Choice 2005

> http://mail.

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Share on other sites

Hi Al:

Of course we would all be delighted if we could take a supplement

that would have the same effects on lifespan as CR.

But given all the bad things that are being said about what body fat,

just by way of its existence, does to cause all kinds of trouble, one

wonders whether the mimetic would also have to reduce body

fat ............ without restraint of food intake.

That would seem to be a tall order if the -Benedict kind of

analyses of the relationship between food intake a body weight are

meaningful - I.E. that for any level of caloric intake sustained on

average over a long period there is a corresponding equilibrium body

weight AEE (all else equal).

How can we eat as much as we want, take a CR mimetic supplement, and

not have excessive body fat? If there's a way I'd sure like to know

about it.

Rodney.

--- In , Al Pater <old542000@y...>

wrote:

> Hi All,

>

> How closely is the altered expression of genes affected by CR shown

by its memetics?

> The results may impress.

>

> See the not pdf-available abstract of the paper below.

>

> Dhahbi JM, Mote PL, Fahy GM, Spindler SR.

> Identification of potential caloric restriction mimetics by

microarray profiling.

> Physiol Genomics. 2005 Sep 27; [Epub ahead of print]

> PMID: 16189280

>

> To facilitate the development of assays for the discovery of

pharmaceuticals capable

> of mimicking the effects of caloric restriction on life- and

healthspan (CR

> mimetics), we evaluated the effectiveness of glucoregulatory and

putative cancer

> chemopreventatives in reproducing the hepatic gene-expression

profile produced by

> long-term CR (LTCR) using Affymetrix microarrays. We have shown

that CR initiated

> late in life begins to extend lifespan, reduce cancer as a cause of

death, and

> reproduce ~three quarters of the genomic effects of LTCR in 8 weeks

(CR8). Eight

> weeks of metformin treatment was superior to CR8 at reproducing

LTCR-like gene

> expression changes, maintaining a superior number of such changes

over a broad range

> of statistical stringencies, and producing more gene ontology terms

overlapping

> those produced by LTCR. Consistent with these results, metformin

has been shown to

> reduce cancer incidence in mice and humans. Phenformin, a chemical

cousin of

> metformin, extends lifespan and reduces tumor incidence in mice.

Taken together,

> these results indicate that gene-expression biomarkers can be used

to identify

> promising candidate CR mimetics.

>

> Al Pater, PhD; email: old542000@y...

>

>

>

> __________________________________

> - PC Magazine Editors' Choice 2005

> http://mail.

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