An in vitro model of caloric restriction

Cabo, Rafael de; Fürer-Galbán, Stefanie; Anson, R. Michael; Gilman, Charles; Gorospe, Myriam; Lane, Mark A.

doi:10.1016/s0531-5565(03)00055-x

Cited by 103 publications

(93 citation statements)

References 29 publications

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“…To identify potential CR mimetic drugs, we retrieved a CR transcriptional profile from published data in rat cells exposed to sera from rats or rhesus monkeys undergoing CR (de Cabo et al ., 2003). The transcriptional profile was used to query the CMap to identify drugs that induce similar or opposite profiles (see Experimental procedures).…”

Section: Resultsmentioning

confidence: 99%

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A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans

et al. 2015

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SummaryCaloric restriction (CR), a reduction in calorie intake without malnutrition, retards aging in several animal models from worms to mammals. Developing CR mimetics, compounds that reproduce the longevity benefits of CR without its side effects, is of widespread interest. Here, we employed the Connectivity Map to identify drugs with overlapping gene expression profiles with CR. Eleven statistically significant compounds were predicted as CR mimetics using this bioinformatics approach. We then tested rapamycin, allantoin, trichostatin A, LY‐294002 and geldanamycin in Caenorhabditis elegans. An increase in lifespan and healthspan was observed for all drugs except geldanamycin when fed to wild‐type worms, but no lifespan effects were observed in eat‐2 mutant worms, a genetic model of CR, suggesting that life‐extending effects may be acting via CR‐related mechanisms. We also treated daf‐16 worms with rapamycin, allantoin or trichostatin A, and a lifespan extension was observed, suggesting that these drugs act via DAF‐16‐independent mechanisms, as would be expected from CR mimetics. Supporting this idea, an analysis of predictive targets of the drugs extending lifespan indicates various genes within CR and longevity networks. We also assessed the transcriptional profile of worms treated with either rapamycin or allantoin and found that both drugs use several specific pathways that do not overlap, indicating different modes of action for each compound. The current work validates the capabilities of this bioinformatic drug repositioning method in the context of longevity and reveals new putative CR mimetics that warrant further studies.

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Section: Resultsmentioning

confidence: 99%

“…A list of 41 DEGs from rat cell lines exposed to Fisher 344 rat and rhesus monkey sera from CR states (compared to cells exposed to sera from ad libitum animals) was collected from the literature (de Cabo et al ., 2003). Using HomoloGene (NCBI Resource Coordinators 2014), only genes with human homologues were kept (39 genes in total).…”

Section: Methodsmentioning

confidence: 99%

A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans

et al. 2015

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“…Numerous changes in blood chemistry have also been documented in animals and humans maintained on CR including decreased levels of insulin, glucose, triglycerides, and markers of oxidative stress (44). We previously reported that when cultured cells are incubated in serum from CR animals they exhibit increased resistance to oxidative stress, which was associated with up-regulation of the expression of HSP-70 compared with cells incubated in serum from AL animals (32). The latter study provided evidence that reduced levels of insulin and IGF-1 in CR serum contribute to the anti-aging stress-resistant phenotype, consistent with the insulin signaling hypothesis of aging (45).…”

Section: Discussionmentioning

confidence: 99%

“…Cells were maintained at 37°C under a humidified 5% CO 2 and 95% O 2 air atmosphere. AL and CR sera were prepared as described previously (32).…”

Section: Methodsmentioning

confidence: 99%

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Calorie restriction up-regulates the plasma membrane redox system in brain cells and suppresses oxidative stress during aging

Hyun

Emerson

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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The plasma membrane (PM) contains redox enzymes that provide electrons for energy metabolism and recycling of antioxidants such as coenzyme Q and ␣-tocopherol. Brain aging and neurodegenerative disorders involve impaired energy metabolism and oxidative damage, but the involvement of the PM redox system (PMRS) in these processes is unknown. Caloric restriction (CR), a manipulation that protects the brain against aging and disease, increased activities of PMRS enzymes (NADH-ascorbate free radical reductase, NADH-quinone oxidoreductase 1, NADH-ferrocyanide reductase, NADH-coenzyme Q10 reductase, and NADH-cytochrome c reductase) and antioxidant levels (␣-tocopherol and coenzyme Q10) in brain PM during aging. Age-related increases in PM lipid peroxidation, protein carbonyls, and nitrotyrosine were attenuated by CR, levels of PMRS enzyme activities were higher, and markers of oxidative stress were lower in cultured neuronal cells treated with CR serum compared with those treated with ad libitum serum. These findings suggest important roles for the PMRS in protecting brain cells against age-related increases in oxidative and metabolic stress.Alzheimer's disease ͉ reactive oxygen species ͉ coenzyme Q10 ͉ oxidoreductase

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Weight Loss and Diet

Levine¹,

Levine²

2012

Metabolic Syndrome and Cardiovascular Disease

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An in vitro model of caloric restriction

Cited by 103 publications

References 29 publications

A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans

A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans

Calorie restriction up-regulates the plasma membrane redox system in brain cells and suppresses oxidative stress during aging

Weight Loss and Diet

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