Calorie restriction (CR) increases longevity in many species by unknown mechanisms. The circadian clock was proposed as a potential mediator of CR. Deficiency of the core component of the circadian clock--transcriptional factor BMAL1 (brain and muscle ARNT [aryl hydrocarbon receptor nuclear translocator]-like protein 1)-results in accelerated aging. Here we investigated the role of BMAL1 in mechanisms of CR. The 30% CR diet increased the life span of wild-type (WT) mice by 20% compared to mice on an ad libitum (AL) diet but failed to increase life span of Bmal1 2/2 mice. BMAL1 deficiency impaired CR-mediated changes in the plasma levels of IGF-1 and insulin. We detected a statistically significantly reduction of IGF-1 in CR vs. AL by 50 to 70% in WT mice at several daily time points tested, while in Bmal1 2/2 the reduction was not significant. Insulin levels in WT were reduced by 5 to 9%, while Bmal1 2/2 induced it by 10 to 35% at all time points tested. CR up-regulated the daily average expression of Bmal1 (by 150%) and its downstream target genes Periods (by 470% for Per1 and by 130% for Per2). We propose that BMAL1 is an important mediator of CR, and activation of BMAL1 might link CR mechanisms with biologic clocks.-Patel, S. A., Chaudhari, A., Gupta, R., Velingkaar, N., Kondratov, R. V. Circadian clocks govern calorie restriction-mediated life span extension through BMAL1-and IGF-1-dependent mechanisms. FASEB J. 30, 1634-1642 (2016). www.fasebj.orgCalorie restriction (CR) is a robust intervention that increases longevity across different species, including mammals (1-4). The precise molecular mechanisms of CR are unknown, and multiple theories have been put forward to explain CR-mediated effects on life span and health. Several physiologic systems-such as the mammalian target of rapamycin (mTOR) signaling pathway, the insulin/IGF-1 signaling pathways, and the sirtuin-controlled pathway-are affected by CR in animals and are considered to be potential mediators of CR (5-7). Activation of the NADdependent protein deacetylase sirtuin (silent mating type information regulation 2 homolog) 1 (SIRT1) is necessary for the full benefits of CR (8-11). Indeed, several behavioral and physiologic changes induced by CR in wild-type (WT) mice are impaired in SIRT1-null mice: these animals do not demonstrate an increase in daily activity (12). CR has different effects on several metabolic parameters in WT and SIRT1-null mice (13,14). Finally, there is no increase in the life span of SIRT1-null mice on CR (14).SIRT1 regulates the activity of many transcription factors. The helix-loop-helix transcription factor BMAL1 (brain and muscle ARNT [aryl hydrocarbon receptor nuclear translocator]-like protein 1) is one of the direct targets of SIRT1 (15). BMAL1 is a component of the circadian clock mechanism (16). The circadian clock is an internal timekeeping system that generates daily rhythms in physiology, metabolism, and behavior (17)(18)(19)(20). BMAL1 also has other physiologic functions, such as control of metabolism, g...

The circadian clock regulates IGF-1 production and signaling through proteins called cryptochromes, which regulate the activity of transcriptional factor STAT5B and control mouse body and organ size.

Background: Estimating the seroprevalence of HIV in a low risk population such as pregnant women provides essential information for an effective implementation of AIDS control programmes, and also for the monitoring of HIV spread within a country. Very few studies are available from north India showing the current trend in HIV prevalence in the antenatal population;which led us to carry outthis study at a tertiary care hospital in north India

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