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title="Dismiss find">✘</a></nav><nav id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK2331_"><span class="title" itemprop="name">Do brains have a freshness date?</span></h1><div class="subtitle whole_rhythm">the effect of aging on the human brain</div><p class="contribs">Sutton V.</p><p class="fm-aai"><a href="#_NBK2331_pubdet_">Publication Details</a></p></div></div><div class="body-content whole_rhythm" itemprop="text"><p>As humans age, many bodily functions and abilities change. Scientists have long been interested in discovering how aging produces a decline in brain function and contributes to the development of certain diseases. To investigate the molecular shifts that occur in the brain during aging, some recent studies have focused on changes in gene expression patterns, both in humans and in other animals.</p><p>
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</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figA665" co-legend-rid="figlgndA665"><a href="/books/NBK2331/figure/A665/?report=objectonly" target="object" title="Figure" class="img_link icnblk_img figpopup" rid-figpopup="figA665" rid-ob="figobA665"><img class="small-thumb" src="/books/NBK2331/bin/cb28_big.gif" src-large="/books/NBK2331/bin/cb28_big.jpg" alt="The gene expression in human brains changes with age, with some genes decreasing expression while others increase" /></a><div class="icnblk_cntnt" id="figlgndA665"><h4 id="A665"><a href="/books/NBK2331/figure/A665/?report=objectonly" target="object" rid-ob="figobA665">Figure</a></h4><p class="float-caption no_bottom_margin">The gene expression in human brains changes with age, with some genes decreasing expression while others increase. This is illustrated by a chart of the expression of the gene MAP1B, which shows high levels expression in the young, variable levels of <a href="/books/NBK2331/figure/A665/?report=objectonly" target="object" rid-ob="figobA665">(more...)</a></p></div></div><p>A recent study by Lu et al. (<a class="bibr" href="#A655" rid="A655">1</a>) compared the levels of gene expression in postmortem brain samples from young and old human subjects. The gene expression profiles were clustered into three broad groups: young (below 40 years), intermediate (40-70 years), and old (70+ years) (see data at the <a href="/geo/gds/gds_browse.cgi?gds=707" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Gene Expression Omnibus</a>) (<a class="bibr" href="#A656" rid="A656">2</a>). Whereas the young and old subjects were relatively homogeneous in their gene expression profiles, the intermediate group was much more heterogeneous, with vastly different rates of progression through the transition from the young gene expression profile to the old profile. </p><p>In older brains, the expression of genes involved in learning and memory, neuronal survival, and maintenance was decreased. Among these were the genes coding for microtubule-associated protein MAP1B, which stabilizes microtubules and promotes axonal growth (<a class="bibr" href="#A657" rid="A657">3</a>,<a class="bibr" href="#A658" rid="A658">4</a>) (see <a href="/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4131" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Entrez Gene</a> entry, <a href="/entrez/query.fcgi?CMD=search&DB=geo&term=41373_s_at%20AND%20gds707" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GEO data</a>); MEF2C (see <a href="/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4208" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Entrez Gene</a> entry, <a href="/entrez/query.fcgi?CMD=search&DB=geo&term=37712_g_at%20AND%20gds707" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GEO data</a>), which promotes the survival of neurons (<a class="bibr" href="#A655" rid="A655">1</a>); subunit 2A of the glutamate receptor NMDAR (see <a href="/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=2903" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Entrez Gene</a> entry, <a href="/entrez/query.fcgi?CMD=search&DB=geo&term=38236_at%20AND%20gds707" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GEO data</a>), which is centrally involved in synaptic plasticity, the brain-restructuring process used in learning and memory; and calmodulin 1 (see <a href="/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=801" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Entrez Gene</a> entry, <a href="/entrez/query.fcgi?CMD=search&DB=geo&term=41144_g_at%20%20AND%20gds707" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GEO data</a>), which is a central regulator of calcium-mediated signaling and plays an important role in memory. In contrast, the expression of genes coding for proteins involved in sensing and responding to cellular stresses increased, suggesting that older brains are exposed to higher levels of damaging stressors than are young brains (<a class="bibr" href="#A655" rid="A655">1</a>). For example, one of the genes more highly expressed in older brains was the DNA repair enzyme OGG1 (see <a href="/entrez/query.fcgi?db=gene&cmd=retrieve&dopt=default&list_uids=4968" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Entrez Gene</a> entry, <a href="/entrez/query.fcgi?CMD=search&DB=geo&term=38335_at%20%20AND%20gds707" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">GEO data</a>), which targets oxidatively damaged DNA.</p><p>Similar studies have been performed with a range of other animals, including <i>Caenorhabditis elegans</i>, <i>Drosophila melogaster</i>
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(<a class="bibr" href="#A659" rid="A659">5</a>), and mice (<a class="bibr" href="#A660" rid="A660">6</a>,<a class="bibr" href="#A661" rid="A661">7</a>). Although the affected genes were not the same among all of the systems, the functional systems of the cells were affected in similar ways across species. For example, in the brains of both mice and humans, the expression of genes involved in synaptic function was decreased, whereas those involved in stress responses increased.</p><p>Further investigation of the genes whose expression was decreased in older human subjects showed that the promoters of these genes were more susceptible to oxidative damage than other genes tested (<a class="bibr" href="#A655" rid="A655">1</a>), suggesting a mechanism for the observed decreased gene expression. Oxidative damage is caused by oxidants such as superoxide and hydrogen peroxide, which are produced as natural by-products of cell metabolism (<a class="bibr" href="#A662" rid="A662">8</a>). The cell has response systems specifically dedicated to sensing and destroying such oxidants, as well as systems to repair any damage caused by those oxidants. It has long been hypothesized that oxidants play a role in aging processes, but this has proved difficult to demonstrate directly (<a class="bibr" href="#A663" rid="A663">9</a>). The variable gene expression profiles (<a class="bibr" href="#A655" rid="A655">1</a>) of the intermediate-age group suggest that oxidative damage may accumulate over a long period of time, with the effects occurring long after the initial oxidative damage is inflicted. </p><p>Perhaps some of the effects of aging can be slowed or lessened by controlling the level of oxidative stress in the cell; many methods are currently under investigation for reducing the creation of oxidants during metabolism. These include calorie restriction (currently being tested in <a href="http://www.clinicaltrials.gov/ct/search?term=caloric+restriction+OR+food+restriction&recruiting=false" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">clinical trials</a>, see <a href="http://www.cnn.com/2003/HEALTH/11/07/calories.aging/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">news coverage</a>) (<a class="bibr" href="#A664" rid="A664">10</a>), the use of antioxidant supplements, and a wide range of methods designed to target various cellular and molecular processes to safely and effectively reduce the production of oxidants during metabolism (<a class="bibr" href="#A664" rid="A664">10</a>). Another potentially fruitful therapeutic strategy is to enhance DNA repair in cells to slow the accumulation of oxidative damage in the DNA. Because the results outlined by Lu et al. (<a class="bibr" href="#A664" rid="A664">10</a>) show that after the age of about 40 years, humans may begin to exhibit age-related changes in gene expression, some treatments might be more effective in young patients than in those already experiencing the effects of aging. The challenge for future scientific investigation will be to find effective treatments for increasing life expectancy while ensuring high quality of life.</p><p>
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<i>This Coffee Break was contributed by Victoria Sutton, PhD, while on rotation at the National Center for Biotechnology Information as a part of the Emerging Leaders Program from the Department of Health and Human Services (DHSS).</i>
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</p><div id="A666" class="box boxed-text-box whole_rhythm hide-overflow"><h3><span class="title">Aging and the Human Brain</span></h3><p>The changes in gene expression that underlie the effects of aging in humans</p><p>
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<div class="mp-outer"><div class="mp-inner"><embed wmode="opaque" pluginspage="http://www.adobe.com/go/getflashplayer" menu="0" bgcolor="#FFFFFF" quality="high" type="application/x-shockwave-flash" width="601" height="530" src="/books/NBK2331/bin/AGING.swf" /></div></div>
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</p><p>For this tutorial, you will need the latest version of <a href="http://www.macromedia.com/go/getflashplayer" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri">Flash player</a> installed on your computer.</p></div><div id="N0x1d36590N0x35e1b58"><h2 id="_N0x1d36590N0x35e1b58_">References</h2><dl class="temp-labeled-list"><dl class="bkr_refwrap"><dt>1.</dt><dd><div class="bk_ref" id="A655">Lu T . et al. Gene regulation and DNA damage in the ageing human brain. <span><span class="ref-journal">Nature. </span>2004;<span class="ref-vol">429</span>:883–891.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15190254" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15190254</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>2.</dt><dd><div class="bk_ref" id="A656">Barrett T . et al. NCBI GEO: Mining millions of expression profiles - database and tools. <span><span class="ref-journal">Nucleic Acids Research. </span>2005;<span class="ref-vol">33</span>:D562–D566.</span> [<a href="/pmc/articles/PMC539976/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC539976</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/15608262" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15608262</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>3.</dt><dd><div class="bk_ref" id="A657">Black M M , Slaughter T , Fischer I . et al. Microtubule-associated protein 1b (MAP1b) is concentrated in the distal region of growing axons. <span><span class="ref-journal">J Neurosci. </span>1994;<span class="ref-vol">14</span>:857–870.</span> [<a href="/pmc/articles/PMC6576811/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC6576811</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/8301365" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 8301365</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>4.</dt><dd><div class="bk_ref" id="A658">Gonzalez-Billault C . et al. Microtubule-associated protein 1B function during normal development, regeneration, and pathological conditions in the nervous system. <span><span class="ref-journal">J Neurobiol. </span>2004;<span class="ref-vol">58</span>:48–59.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14598369" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14598369</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>5.</dt><dd><div class="bk_ref" id="A659">McCarroll S A . et al. Comparing genomic expression patterns across species identifies shared transcriptional profile in aging. <span><span class="ref-journal">Nat Genet. </span>2004;<span class="ref-vol">36</span>:197–204.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14730301" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14730301</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>6.</dt><dd><div class="bk_ref" id="A660">Lee C K , Weindruch R , Prolla T A . et al. Gene-expression profile of the ageing brain in mice. <span><span class="ref-journal"> Nat Genet. </span>2000;<span class="ref-vol">25</span>:294–297.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/10888876" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 10888876</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>7.</dt><dd><div class="bk_ref" id="A661">Jiang C H , Tsien J Z , Schultz P G . et al. The effects of aging on gene expression in the hypothalamus and cortex of mice. <span><span class="ref-journal">Proc Natl Acad Sci. </span>2001;<span class="ref-vol">98</span>:1930–1934.</span> [<a href="/pmc/articles/PMC29359/" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pmc">PMC free article<span class="bk_prnt">: PMC29359</span></a>] [<a href="https://pubmed.ncbi.nlm.nih.gov/11172053" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 11172053</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>8.</dt><dd><div class="bk_ref" id="A662">Fridovich I . et al. Mitochondria: are they the seat of senescence? <span><span class="ref-journal">Aging Cell. </span>2004;<span class="ref-vol">3</span>:13–16.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14965350" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14965350</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>9.</dt><dd><div class="bk_ref" id="A663">Van Voorhies W A . et al. Live fast--live long? A commentary on a recent paper by Speakman et al. <span><span class="ref-journal">Aging Cell. </span>2004;<span class="ref-vol">3</span>:327–330.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/15379856" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 15379856</span></a>]</div></dd></dl><dl class="bkr_refwrap"><dt>10.</dt><dd><div class="bk_ref" id="A664">Merry B J . et al. Oxidative stress and mitochondrial function with aging--the effects of calorie restriction. <span><span class="ref-journal">Aging Cell. </span>2004;<span class="ref-vol">3</span>:7–12.</span> [<a href="https://pubmed.ncbi.nlm.nih.gov/14965349" ref="pagearea=cite-ref&targetsite=entrez&targetcat=link&targettype=pubmed">PubMed<span class="bk_prnt">: 14965349</span></a>]</div></dd></dl></dl></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK2331_pubdet_">Publication Details</h2><h3>Author Information and Affiliations</h3><p class="contrib-group"><h4>Authors</h4><span itemprop="author">Victoria Sutton</span>, PhD.</p><h3>Publication History</h3><p class="small">Created: <span itemprop="datePublished">January 12, 2005</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><a href="http://www.ncbi.nlm.nih.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Center for Biotechnology Information (US)</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>Sutton V. Do brains have a freshness date?the effect of aging on the human brain. 2005 Jan 12. In: Dean L, McEntyre J, editors. Coffee Break: Tutorials for NCBI Tools [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 1999-. <span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/coffeebrk/cb29_snapper/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/coffeebrk/A643/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="fig" id="figobA665"><div id="A665" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK2331/bin/cb28_big.jpg" alt="The gene expression in human brains changes with age, with some genes decreasing expression while others increase" /></div><div class="caption"><p>The gene expression in human brains changes with age, with some genes decreasing expression while others increase. This is illustrated by a chart of the expression of the gene MAP1B, which shows high levels expression in the young, variable levels of expression at intermediate ages, and greatly reduced expression in older people. For more information about the chart, please visit the tutorial on "<a href="/books/NBK2331/box/A666/?report=objectonly" target="object" rid-ob="figobA666">Aging and the Human Brain</a>".</p></div></div></article><article data-type="boxed-text" id="figobA666"><div id="A666" class="box boxed-text-box whole_rhythm hide-overflow"><h3><span class="title">Aging and the Human Brain</span></h3><p>The changes in gene expression that underlie the effects of aging in humans</p><p>
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