Genes regulated by caloric restriction have unique roles within transcriptional networks

Swindell, William R.

doi:10.1016/j.mad.2008.06.001

Cited by 24 publications

(21 citation statements)

References 132 publications

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“…For instance, CR increased Mt1 expression of in GH-treated Prop1 ( df / df ) mice (P = 0.004, Tukey post-hoc comparison), but this effect was not observed in GH-treated wild-type mice (P = 0.489, two-sample t-test; P = 0.998, Tukey post-hoc comparison). Across the same treatment groups, Mt2 exhibited a very similar pattern of gene expression (data not shown), which was expected because Mt1 and Mt2 are co-expressed in most tissues (Swindell, 2008b). …”

Section: Resultssupporting

confidence: 52%

In vivo analysis of gene expression in long-lived mice lacking the pregnancy-associated plasma protein A (PappA) gene

Masternak

Bartke

2010

Experimental Gerontology

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Mice lacking the pregnancy-associated plasma protein A (PappA) gene exhibit diminished localized IGF-1 bioavailability and a 30% increase in mean life span. However, it is uncertain which tissues exhibit reduced IGF-1 signals in the PappA(−/−) mouse, and whether effects of this mutation parallel those of mutations that diminish IGF-1 in serum. Across a panel of 21 tissues, we used RT-PCR to evaluate the effects of the PappA(−/−) mutation on expression of Igfbp5, which served as an in vivo indicator of IGF-1 signaling. Among these tissues, expression of Igfbp5 was significantly reduced by PappA(−/−) only in kidney. A broader survey of IGF-associated genes in six organs identified five other genes responsive to PappA(−/−) in kidney, with stronger effects in this organ relative to other tissues. Renal expression of Irs1 and Mt1 was increased by PappA(−/−) as well as by mutations that reduce IGF-1 in serum (i.e., Ghr(−/−), Pit1(dw/dw) and Prop1(df/df)), and we demonstrate that expression of these genes is regulated by growth hormonetreatment and calorie restriction. These results provide in vivo data on an important new model of mammalian aging, and characterize both similar and contrasting expression patterns between longlived mice with reduced local IGF-1 availability and diminished IGF-1 in serum.

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Section: Resultssupporting

confidence: 52%

In vivo analysis of gene expression in long-lived mice lacking the pregnancy-associated plasma protein A (PappA) gene

Masternak

Bartke

2010

Experimental Gerontology

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“…Dhahbi et al have shown smaller cardiomyocytes and reduced collagen accumulation in caloric restricted mice 84. Interestingly, reduced expression levels of pro-collagen genes in caloric restricted mice have also been shown by other investigators 85.…”

Section: Discussionmentioning

confidence: 74%

Smaller cardiac cell size and reduced extra-cellular collagen might be beneficial for hearts of Ames dwarf mice

Helms¹,

Azhar²,

Zuo³

et al. 2010

Int. J. Biol. Sci.

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Purpose: To test the hypothesis that cardiac morphologic differences between Ames dwarf and wild-type littermates might correlate with the increased longevity observed in the Ames dwarf mice.Methods: Hearts removed from young adult (5-7 mo) and old (24-28 mo) Ames dwarf and wild-type littermates underwent histological and morphometric analysis. Measurements of cell size, nuclear size, and collagen content were made using computerized color deconvolution and particle analysis methodology.Results: In the young mice at six months of age, mean cardiomyocyte area was 46% less in Ames dwarf than in wild-type mice (p<0.0001). Cardiomyocyte size increased with age by about 52% in the wild-type mice and 44% in the Ames dwarf mice (p<0.001). There was no difference in nuclear size of the cardiomyocytes between the young adult wild-type and Ames dwarf mice. There was an age-associated increase in the cardiomyocyte nuclear size by approximately 50% in both the Ames and wild-type mice (p<0.001). The older Ames dwarf mice had slightly larger cardiomyocyte nuclei compared to wild-type (2%, p<0.05). The collagen content of the hearts in young adult Ames dwarf mice was estimated to be 57% less compared to wild-type littermates (p<0.05). Although collagen content of both Ames dwarf and wild-type mouse hearts increased with age, there was no significant difference at 24 months.Conclusions: In wild-type and Ames dwarf mice, nuclear size, cardiomyocyte size, and collagen content increased with advancing age. While cardiomyocyte size was much reduced in young and old Ames dwarf mice compared with wild-type, collagen content was reduced only in the young adult mice. Taken together, these findings suggest that Ames dwarf mice may receive some longevity benefit from the reduced cardiomyocyte cell size and a period of reduced collagen content in the heart during adulthood.

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“…Mouse Mt1 and Mt2 genes are best conserved across species and are widely expressed with a correlated expression pattern across most tissues (Figure 2). The partly shared expression pattern of Mt1 and Mt2 is distinct from that of most other mouse genes, such that Mt1 and Mt2 have few other genes that can be considered as close “neighbors” within the genome-wide transcriptional network (Swindell, 2008b). Expression of Mt1 and Mt2 is highest in pancreas, prostate and spinal cord, and weakest in thymocytes and T cells (Figure 2).…”

Section: Metallothionein: a Quick Review (Or Introduction) For Thementioning

confidence: 99%

Metallothionein and the biology of aging

Swindell

2011

Ageing Research Reviews

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Metallothionein (MT) is a low molecular weight protein with anti-apoptotic properties that has been demonstrated to scavenge free radicals in vitro. MT has not been extensively investigated within the context of aging biology. The purpose of this review, therefore, is to discuss findings on MT that are relevant to basic aging mechanisms and to draw attention to the possible role of MT in pro-longevity interventions. MT is one of just a handful of proteins that, when overexpressed, has been demonstrated to increase mouse lifespan. MT also protects against development of obesity in mice provided a high fat diet as well as diet-induced oxidative stress damage. Abundance of MT is responsive to caloric restriction (CR) and inhibition of the insulin / insulin-like signaling (IIS) pathway, and elevated MT gene expression has been observed in tissues from fasted and CR-fed mice, long-lived dwarf mice, worms maintained under CR conditions, and long-lived daf-2 mutant worms. The dysregulation of MT in these systems is likely to have tissue-specific effects on aging outcomes. Further investigation will therefore be needed to understand how MT contributes to the response of invertebrates and mice to CR and the endocrine mutations studied by aging researchers.

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Genes regulated by caloric restriction have unique roles within transcriptional networks

Cited by 24 publications

References 132 publications

In vivo analysis of gene expression in long-lived mice lacking the pregnancy-associated plasma protein A (PappA) gene

In vivo analysis of gene expression in long-lived mice lacking the pregnancy-associated plasma protein A (PappA) gene

Smaller cardiac cell size and reduced extra-cellular collagen might be beneficial for hearts of Ames dwarf mice

Metallothionein and the biology of aging

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