X-Message-Number: 30097
Date: Mon, 3 Dec 2007 18:23:35 -0800 (PST)
From: 
Subject: aging processes in mice and humans may be fundamentally diffe...

Molecular Map Helps Illuminate Why Mice Only Live For Two Years
ScienceDaily (Dec. 3, 2007) - Researchers at the National Institute of Aging
and Stanford University have used gene arrays to identify genes whose
activity changes with age in 16 different mouse tissues. The study uses a
newly available database called AGEMAP to document the process of aging in
mice at the molecular level. The work describes how aging affects different
tissues in mice, and ultimately could help explain why lifespan is limited
to just two years in mice.

As an organism ages, most tissues change their structure (for example,
muscle tissues become weaker and have slow twitch rather than fast twitch
fibers), and all tissues are subject to cellular damage that accumulates
with age. Both changes in tissues and cellular damage lead to changes in
gene expression, and thus probing which genes change expression in old age
can lead to insights about the process of aging itself.
Previous studies have studied gene expression changes during aging in just
one tissue. The new work stands out because it is much larger and more
complete, including aging data for 16 different tissues and containing over
5.5 million expression measurements.
One noteworthy result is that some tissues (such as the thymus, eyes and
lung) show large changes in which genes are active in old age whereas other
tissues (such as liver and cerebrum) show little or none, suggesting that
different tissues may degenerate to different degrees in old mice.
Another insight is that there are three distinct patterns of aging, and that
tissues can be grouped according to which aging pathway they take. This
result indicates that there are three different clocks for aging that may or
may not change synchronously, and that an old animal may be a mixture of
tissues affected by each of the different aging clocks.
Finally, the report compares aging in mice to aging in humans. Several aging
pathways were found to be the same, and these could be interesting because
they are relevant to human aging and can also be scientifically studied in
mice.
Journal citation: Zahn JM, Poosala S, Owen AB, Ingram DK, Lustig A, et al.
(2007) AGEMAP: A gene expression database for aging in mice. PLoS Genet
3(11): e201. doi:10.1371/journal.pgen.0030201



http://genetics.plosjournals.org/archive/1553-7404/3/11/pdf/10.1371_journal.pgen.0030201-L.pdf

AGEMAP: A Gene Expression Database for Aging in Mice
  Jacob M. Zahn1, Suresh Poosala2, Art B. Owen3, Donald K. Ingram2, Ana
Lustig2, Arnell Carter2, Ashani T. Weeraratna2, Dennis D. Taub2, Myriam
Gorospe2, Krystyna Mazan-Mamczarz2, Edward G. Lakatta2, Kenneth R. Boheler2,
Xiangru Xu2, Mark P. Mattson2, Geppino Falco2, Minoru S. H. Ko2, David
Schlessinger2, Jeffrey Firman2, Sarah K. Kummerfeld1, William H. Wood III2,
Alan B. Zonderman2, Stuart K. Kim1,4*, Kevin G. Becker2*
1 Department of Developmental Biology, Stanford University Medical Center,
Stanford, California, United States of America, 2 National Institute on
Aging, National Institutes of Health, Baltimore, Maryland, United States of
America, 3 Department of Statistics, Stanford University, Stanford,
California, United States of America, 4 Department of Genetics, Stanford
University Medical Center, Stanford, California, United States of America
  We present the AGEMAP (Atlas of Gene Expression in Mouse Aging
Project) gene expression database, which is a resource that catalogs
changes in gene expression as a function of age in mice. The AGEMAP
database includes expression changes for 8,932 genes in 16 tissues as a
function of age. We found great heterogeneity in the amount of
transcriptional changes with age in different tissues. Some tissues
displayed large transcriptional differences in old mice, suggesting that
these tissues may contribute strongly to organismal decline. Other tissues
showed few or no changes in expression with age, indicating strong levels
of homeostasis throughout life. Based on the pattern of age-related
transcriptional changes, we found that tissues could be classified into
one of three aging processes: (1) a pattern common to neural tissues,
(2) a pattern for vascular tissues, and (3) a pattern for
steroid-responsive tissues. We observed that different
tissues age in a coordinated fashion in individual mice, such that certain
mice exhibit rapid aging, whereas others exhibit slow aging for multiple
tissues. Finally, we compared the transcriptional profiles for aging in mice
to those from humans, flies, and worms. We found that genes involved in the
electron transport chain show common age regulation in all four species,
indicating that these genes may be exceptionally good markers of aging.
However, we saw no overall correlation of age regulation between mice and
humans, suggesting that aging processes in mice and humans may be
fundamentally different.

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