DNA MICROARRAYS AS A SCREENING TOOL FOR CALORIC RESTRICTION MIMETIC INTERVENTIONS
R. Weindruch* and T.A. Prolla
Departments of Medicine [RW] and Genetics [TAP]
University of Wisconsin-Madison
Madison, WI 53706
To examine the molecular events associated with aging in mammals, we
employed oligonucleotide based arrays to define the transcriptional
response to the aging process in mouse gastrocnemius muscle and in two
regions of the brain (cerebellum, neocortex). We also studied the
influence of retarded mammalian aging induced by caloric restriction
(CR) on transcriptional patterns in these tissues. Our choice of
tissues was guided by the fact that skeletal muscle and the brain are
primarily composed of long-lived, high oxygen-consuming postmitotic
cells, a feature shared with another critical aging target (the heart).
We observed two types of changes in mice subjected to CR:
1) Prevention of age-associated changes in gene expression. For
example, in the gastrocnemius ~70% of the largest changes in gene
expression observed with aging were prevented (either totally or
partially) by CR.
2) Shifting the level of expression of genes which did not show changes
with age. This type of effect can be thought of as CR induced
"transcriptional reprogramming" and involved many genes that encode
proteins with metabolic functions.
These two types of transcriptional effects induced by CR can be used to
create panels of molecular markers for evaluating the extent to which
an intervention mimics CR at the level of gene expression. This
approach may facilitate the development of interventions which retard
the rate of aging in individual organs.
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