AGEMAP: A Gene Expression Database for Aging in Mice

Zahn, Jacob M.; Poosala, Suresh; Owen, Art B.; Ingram, Donald K.; Lustig, Ana; Carter, Arnell; Weeraratna, Ashani T.; Taub, Dennis D.; Gorospe, Myriam; Mazan-Mamczarz, Krystyna; Lakatta, Edward G.; Boheler, Kenneth R.; Xu, Xiangru; Mattson, Mark P.; Falco, Geppino; Ko, Minoru S.H.; Schlessinger, David; Firman, Jeffrey; Kummerfeld, Sarah; Wood, William H.; Zonderman, Alan B.; Kim, Stuart K.; Becker, Kevin G.

doi:10.1371/journal.pgen.0030201

Cited by 356 publications

(298 citation statements)

References 36 publications

(38 reference statements)

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“…Several studies, most notably the groundbreaking AGEMAP (Atlas of Gene Expression in Mouse Aging Project) study, have examined the effect of age on gene expression in C57BL/6J.Nia mice (Zahn et al ., 2007) in tissues including liver, muscle, and heart. Notably, neither the AGEMAP study, nor a study published by Pearson et al .…”

Section: Resultsmentioning

confidence: 99%

“…Notably, neither the AGEMAP study, nor a study published by Pearson et al . (2008) comparing the effect of dietary interventions on the aging C57BL/6J.Nia male transcriptome, identified the mTOR pathway as significantly affected (Zahn et al ., 2007; Pearson et al ., 2008). …”

Section: Resultsmentioning

confidence: 99%

“… Table S1 GSEA of AGEMAP data (Zahn et al ., 2007) from liver, muscle, and heart using 23 mTOR‐related gene sets. The false discovery rate is shown for each gene set.…”

Section: Supporting Informationmentioning

confidence: 99%

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Sex‐ and tissue‐specific changes in mTOR signaling with age in C57 BL /6J mice

et al. 2015

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SummaryInhibition of the mTOR (mechanistic Target Of Rapamycin) signaling pathway robustly extends the lifespan of model organisms including mice. The precise molecular mechanisms and physiological effects that underlie the beneficial effects of rapamycin are an exciting area of research. Surprisingly, while some data suggest that mTOR signaling normally increases with age in mice, the effect of age on mTOR signaling has never been comprehensively assessed. Here, we determine the age‐associated changes in mTORC1 (mTOR complex 1) and mTORC2 (mTOR complex 2) signaling in the liver, muscle, adipose, and heart of C57BL/6J.Nia mice, the lifespan of which can be extended by rapamycin treatment. We find that the effect of age on several different readouts of mTORC1 and mTORC2 activity varies by tissue and sex in C57BL/6J.Nia mice. Intriguingly, we observed increased mTORC1 activity in the liver and heart tissue of young female mice compared to male mice of the same age. Tissue and substrate‐specific results were observed in the livers of HET3 and DBA/2 mouse strains, and in liver, muscle and adipose tissue of F344 rats. Our results demonstrate that aging does not result in increased mTOR signaling in most tissues and suggest that rapamycin does not promote lifespan by reversing or blunting such an effect.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Sex‐ and tissue‐specific changes in mTOR signaling with age in C57 BL /6J mice

et al. 2015

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“…In addition, several reports have found progerin, and increasing levels of progerin, in normal cells over the course of normal aging (Scaffidi & Misteli, 2006; McClintock et al ., 2007; Cao et al ., 2007; Rodriguez et al ., 2009), which suggests a similar genetic mechanism in HGPS and normal aging. Moreover, genome‐scale expression profiling in cells from HGPS patients, as well as in physiological aging, has revealed widespread transcriptional misregulation in multiple mammalian tissues (Ly et al ., 2000; Csoka et al ., 2004; Zahn et al ., 2007; Scaffidi & Misteli, 2008; Cao et al ., 2011; McCord et al ., 2013). …”

Section: Introductionmentioning

confidence: 99%

Global genome splicing analysis reveals an increased number of alternatively spliced genes with aging

et al. 2015

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SummaryAlternative splicing (AS) is a key regulatory mechanism for the development of different tissues; however, not much is known about changes to alternative splicing during aging. Splicing events may become more frequent and widespread genome‐wide as tissues age and the splicing machinery stringency decreases. Using skin, skeletal muscle, bone, thymus, and white adipose tissue from wild‐type C57BL6/J male mice (4 and 18 months old), we examined the effect of age on splicing by AS analysis of the differential exon usage of the genome. The results identified a considerable number of AS genes in skeletal muscle, thymus, bone, and white adipose tissue between the different age groups (ranging from 27 to 246 AS genes corresponding to 0.3–3.2% of the total number of genes analyzed). For skin, skeletal muscle, and bone, we included a later age group (28 months old) that showed that the number of alternatively spliced genes increased with age in all three tissues (P < 0.01). Analysis of alternatively spliced genes across all tissues by gene ontology and pathway analysis identified 158 genes involved in RNA processing. Additional analysis of AS in a mouse model for the premature aging disease Hutchinson–Gilford progeria syndrome was performed. The results show that expression of the mutant protein, progerin, is associated with an impaired developmental splicing. As progerin accumulates, the number of genes with AS increases compared to in wild‐type skin. Our results indicate the existence of a mechanism for increased AS during aging in several tissues, emphasizing that AS has a more important role in the aging process than previously known.

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“…Vascular aging associates with transcriptional changes in gene expression (Zahn et al 2007) that in part are regulated by sirtuin-1 (Sirt1) (Wood et al 2004). Sirt1 belongs to the family of the mammalian homologues of the Sir2 (silent information regulator-2) of the yeast Saccharomyces cerevisiae.…”

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confidence: 99%

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

Tomada

Almeida

et al. 2011

AGE

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Aging and physiological androgen decay leads to structural changes in corpus cavernosum (CC) that associate with erectile function impairment. There is evidence that such changes relate to nitric oxide (NO) bioavailability, an endothelial compound produced by the action of endothelial NO synthase (eNOS), and is regulated by sirtuin-1 (Sirt1), a NAD + -dependent protein deacetylase. Taking into account the reduced NO synthesis observed in aging and erectile dysfunction, we aimed to characterize human CC of androgen-deprived, young, and aged individuals postulating that androgen deprivation induces modifications similar to those observed in aging. Human penile fragments were collected from young individuals submitted to male-to-female sex reassignment procedure, who undergone an androgen deprivation chemical regimen, from young organ donors and from aged patients submitted to penile deviation surgery. They were processed for histomorphometric analysis of smooth muscle (SM) and connective tissues (CT), and dual-immunofluorescence of alpha-actin/vWf or Sirt1, and endothelin-1/eNOS. Estrogen receptors were analyzed by immunohistochemistry and semiquantification of Sirt1, eNOS, and phospho-Akt was assayed by Western blotting. Androgen withdrawal, similarly to aging, leads to a noteworthy reduction of SM-to-CT ratio in CC. However, in contrast to young and aged, a significant increase in penile Sirt1 expression accompanied by an increase in total eNOS expression was observed in androgen-depleted individuals. No changes were evidenced in phospho-Akt system and estrogen receptors were undetectable. These findings indicate that Sirt1 regulates the expression of eNOS in human CC employing mechanisms influenced by androgen depletion.

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AGEMAP: A Gene Expression Database for Aging in Mice

Cited by 356 publications

References 36 publications

Sex‐ and tissue‐specific changes in mTOR signaling with age in C57 BL /6J mice

Sex‐ and tissue‐specific changes in mTOR signaling with age in C57 BL /6J mice

Global genome splicing analysis reveals an increased number of alternatively spliced genes with aging

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

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