Role of CBP and SATB-1 in Aging, Dietary Restriction, and Insulin-Like Signaling

Zhang, Minhua; Poplawski, Michal; Yen, Kelvin; Cheng, Hui; Bloss, Erik B.; Zhu, Xinen; Patel, Harshil B.; Mobbs, Charles V.

doi:10.1371/journal.pbio.1000245

Cited by 103 publications

(156 citation statements)

References 44 publications

Supporting

Mentioning

145

Contrasting

Order By: Relevance

“…TSA has been shown to extend lifespan in C. elegans by about 11% (Zhang et al ., 2009), which is in line with our results (Table S3). One possible mechanism to explain TSA's lifespan extension effects is through the production of nitric oxide (NO).…”

Section: Discussionsupporting

confidence: 93%

“…Additionally, we found three genes so far not associated with longevity which have been suggested to play a role in CR: orthologs of fkb‐6 and gsy‐1 (both targets of rapamycin) are significantly overexpressed in mice under CR (Plank et al ., 2012). Additionally, cbp‐1 (a transcriptional factor that might be affected by TSA) is induced under CR and blocking it results in countering the protective effects of CR (Zhang et al ., 2009). …”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2015

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

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

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Generally, decreased CREB activity was associated with learning impairments in healthy aged animals [31,32] and with cognitive deficits in animal models of neurodegenerative disorders [33][34][35]. Importantly, the level of phosphorylated CREB and the activity-induced increase in CREB phosphorylation is diminished in ageing [36,37], and this itself may influence the ageing process [38,39]. Altered calcium signalling in ageing neurons significantly contributes to diminished CREB activity.…”

Section: Functional Histological and Molecular Changes In The Ageingmentioning

confidence: 99%

The endocannabinoid system in normal and pathological brain ageing

Bilkei-Gorzó

2012

Phil. Trans. R. Soc. B

120

View full text Add to dashboard Cite

The role of endocannabinoids as inhibitory retrograde transmitters is now widely known and intensively studied. However, endocannabinoids also influence neuronal activity by exerting neuroprotective effects and regulating glial responses. This review centres around this less-studied area, focusing on the cellular and molecular mechanisms underlying the protective effect of the cannabinoid system in brain ageing. The progression of ageing is largely determined by the balance between detrimental, proageing, largely stochastic processes, and the activity of the homeostatic defence system. Experimental evidence suggests that the cannabinoid system is part of the latter system. Cannabinoids as regulators of mitochondrial activity, as anti-oxidants and as modulators of clearance processes protect neurons on the molecular level. On the cellular level, the cannabinoid system regulates the expression of brainderived neurotrophic factor and neurogenesis. Neuroinflammatory processes contributing to the progression of normal brain ageing and to the pathogenesis of neurodegenerative diseases are suppressed by cannabinoids, suggesting that they may also influence the ageing process on the system level. In good agreement with the hypothesized beneficial role of cannabinoid system activity against brain ageing, it was shown that animals lacking CB1 receptors show early onset of learning deficits associated with age-related histological and molecular changes. In preclinical models of neurodegenerative disorders, cannabinoids show beneficial effects, but the clinical evidence regarding their efficacy as therapeutic tools is either inconclusive or still missing.

show abstract

“…In the meantime we had been studying mechanisms by which hypothalamic expression of the histone acetyl transferees (HAT) Creb-binding protein (Cbp) regulates lifespan and age-related diseases. These studies arose initially as a result of two high-throughput screens which sought to assess mechanisms by which nutrient-sensitive hypothalamic neurons might mediate the protective effects of dietary restriction during aging [46]. These studies were based on many studies demonstrating that dietary restriction is generally protective during aging, increasing lifespan and delaying age-related diseases (both natural and genetically engineered) in a wide range of species and nutrient-sensitive hypothalamic neurons are uniquely to sense nutritional and cause appropriate systemic responses, which could plausibly mediate these protective effects [47].…”

Section: Discussionmentioning

confidence: 99%

“…In one screen, we examined expression of hypothalamic transcription factors apparently induced by dietary restriction (according to DNA microarray data) across 5 strains of mice, to assess if expression of any of these genes might predict lifespan [46]. Since no single polymorphism could possibly explain more than a small degree of variance of lifespan, we did not have great expectations about this study.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms by Which the Ketogenic Diet Reverses Obesity and Diabetes

Moreno¹

2017

EMIJ

View full text Add to dashboard Cite

Since the beginning of the 20th century, when low-carbohydrate diets were first implemented to treat Type 1 diabetes, the role of dietary composition in regulating glucose homeostasis and, increasingly, energy balance, has been the subject of great interest to both biomedical researchers and, increasingly, to the public. In fairly extreme circumstances (e.g., Type 1 diabetes untreated with insulin) low-carbohydrate diets (which are generally high-fat diets) can be useful to reduce blood glucose, but since the advent of insulin therapy, and increasing appreciation of the cardiovascular consequences of hyperlipidemia, clinical practice has dramatically favored highcarbohydrate, low-fat diets for diabetes (especially Type 2 diabetes, largely associated with obesity). This clinical advice, at the time, seemed fairly radical. In a famous treatise, "The Physiology of Taste" published in 1825, Brillat-Savarin, argue that consumption of "natural" diets (e.g., meat and vegetables) promote health, whereas "cultivated" diet (e.g., derived from rice and wheat) increasingly led to deterioration of health associated with affluence.Similarly, in 1837 Sylvester Graham published "A treatise on bread and breadmaking", essentially a tirade against food with grains (as well as meat), which were not suited to the assumption that gluttony was among the greatest sins (clearly a theme in subsequent American diet fads). Similarly throughout the 20th century popular diets (including those promotes by Adelle Davis in the 1950s, Robert Atkins in the 1970s, the paleo diet, and increasingly many more) have emphasized lowcarbohydrate, high-fat diets especially for weight loss (viewed by the public as a more compelling concern than glucose homeostasis). While these diets have little if any clinical evidence for efficacy, low-calorie, low-protein diets that produce ketogenesis are extremely effective to reverse obesity, hyperglycemia, and diabetic complications. The mini-review examines possible mechanisms mediating these remarkable effects, particularly focusing on epigenetic effects on hypothalamic neurons.

show abstract

Role of CBP and SATB-1 in Aging, Dietary Restriction, and Insulin-Like Signaling

Abstract: Increased transcriptional complex activity, or pharmacological mimics of increased complex activity, predict lifespan in mice and mediate the protective effects of dietary restriction during aging.

Cited by 103 publications

References 44 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

The endocannabinoid system in normal and pathological brain ageing

Mechanisms by Which the Ketogenic Diet Reverses Obesity and Diabetes

Contact Info

Product

Resources

About