Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span

Pearson, Kevin J.; Baur, Joseph A.; Lewis, Kaitlyn N.; Peshkin, Leonid; Price, Nathan L.; Labinskyy, Nazar; Swindell, William R.; Kamara, Davida; Minor, Robin K.; Perez, Evelyn; Jamieson, Hamish A.; Zhang, Yongqing; Dunn, Stephen; Sharma, Kumar; Pleshko, Nancy; Woollett, Laura A.; Csiszár, Anna; Ikeno, Yuji; Couteur, David G. Le; Elliott, Peter J.; Becker, Kevin G.; Navas, Plácido; Ingram, Donald K.; Wolf, Norman S.; Ungvári, Zoltán; Sinclair, David A.; Cabo, Rafael de

doi:10.1016/j.cmet.2008.06.011

Cited by 1,056 publications

(1,001 citation statements)

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“…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%

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%

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

et al. 2015

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“…In addition, resveratrol supplementation in non-human primates increased working (as did CR) and spatial memory performance (Dal-Pan et al 2011). Furthermore, this class of compounds was shown to mimic the effects of CR at the transcriptomic levels notably in reducing signs of aging (Barger et al 2008;Pearson et al 2008;Vidal et al 2011). In fact, polyphenols and resveratrol mediate multiple of the previously described pathways such as SIRTs, AMPK and mTOR (Lam et al 2013).…”

Section: Calorie Restriction Mimetics: the Case Of Polyphenolsmentioning

confidence: 87%

Systems biology approaches to study the molecular effects of caloric restriction and polyphenols on aging processes

et al. 2015

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Worldwide population is aging, and a large part of the growing burden associated with age-related conditions can be prevented or delayed by promoting healthy lifestyle and normalizing metabolic risk factors. However, a better understanding of the pleiotropic effects of available nutritional interventions and their influence on the multiple processes affected by aging is needed to select and implement the most promising actions. New methods of analysis are required to tackle the complexity of the interplay between nutritional interventions and aging, and to make sense of a growing amount of -omics data being produced for this purpose. In this paper, we review how various systems biology-inspired methods of analysis can be applied to the study of the molecular basis of nutritional interventions promoting healthy aging, notably caloric restriction and polyphenol supplementation. We specifically focus on the role that different versions of network analysis, molecular signature identification and multiomics data integration are playing in elucidating the complex mechanisms underlying nutrition, and provide some examples on how to extend the application of these methods using available microarray data.

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“…Some of these chemicals may mimic the effects of DR (Fontana et al, 2010). For example, resveratrol, which induces a similar gene expression profile to dietary restriction (Pearson et al, 2008), can increase lifespan of mice on a high‐calorie diet, although not in mice on a standard diet (Strong et al, 2013). Rapamycin, directly targets the mTORC1 complex, which plays a central role in nutrient‐sensing network and has an important role in lifespan extension by DR (Mair & Dillin, 2008).…”

Section: Introductionmentioning

confidence: 99%

Gene expression‐based drug repurposing to target aging

et al. 2018

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Aging is the largest risk factor for a variety of noncommunicable diseases. Model organism studies have shown that genetic and chemical perturbations can extend both lifespan and healthspan. Aging is a complex process, with parallel and interacting mechanisms contributing to its aetiology, posing a challenge for the discovery of new pharmacological candidates to ameliorate its effects. In this study, instead of a target‐centric approach, we adopt a systems level drug repurposing methodology to discover drugs that could combat aging in human brain. Using multiple gene expression data sets from brain tissue, taken from patients of different ages, we first identified the expression changes that characterize aging. Then, we compared these changes in gene expression with drug‐perturbed expression profiles in the Connectivity Map. We thus identified 24 drugs with significantly associated changes. Some of these drugs may function as antiaging drugs by reversing the detrimental changes that occur during aging, others by mimicking the cellular defence mechanisms. The drugs that we identified included significant number of already identified prolongevity drugs, indicating that the method can discover de novo drugs that meliorate aging. The approach has the advantages that using data from human brain aging data, it focuses on processes relevant in human aging and that it is unbiased, making it possible to discover new targets for aging studies.

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Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span

Cited by 1,056 publications

References 73 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

Systems biology approaches to study the molecular effects of caloric restriction and polyphenols on aging processes

Gene expression‐based drug repurposing to target aging

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