다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

The mechanistic target of rapamycin (mTOR) signaling pathway senses and integrates a variety of environmental cues to regulate organismal growth and homeostasis. The pathway regulates many major cellular processes and is implicated in an increasing number of pathological conditions, including cancer, obesity, type 2 diabetes, and neurodegeneration. Here, we review recent advances in our understanding of the mTOR pathway and its role in health, disease, and aging. We further discuss pharmacological approaches to treat human pathologies linked to mTOR deregulation.

mTOR Signaling in Growth Control and Disease

mTOR signaling in growth control and disease.

Autophagy is a process by which components of the cell are degraded to maintain essential activity and viability in response to nutrient limitation. Extensive genetic studies have shown that the yeast ATG1 kinase has an essential role in autophagy induction. Furthermore, autophagy is promoted by AMP activated protein kinase (AMPK), which is a key energy sensor and regulates cellular metabolism to maintain energy homeostasis. Conversely, autophagy is inhibited by the mammalian target of rapamycin (mTOR), a central cell-growth regulator that integrates growth factor and nutrient signals. Here we demonstrate a molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1. Under glucose starvation, AMPK promotes autophagy by directly activating Ulk1 through phosphorylation of Ser 317 and Ser 777. Under nutrient sufficiency, high mTOR activity prevents Ulk1 activation by phosphorylating Ulk1 Ser 757 and disrupting the interaction between Ulk1 and AMPK. This coordinated phosphorylation is important for Ulk1 in autophagy induction. Our study has revealed a signalling mechanism for Ulk1 regulation and autophagy induction in response to nutrient signalling.

/pdf/ampk-and-mtor-regulate-autophagy-through-direct-14wqsz16ke.pdf

AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.

For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.

Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

/pdf/guidelines-for-the-use-and-interpretation-of-assays-for-ijf2t30pbq.pdf

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Codium fragile (C. fragile) is a marine alga with high functional food potential. Recent studies have proven C. fragile extract (CFE) effective against obesity. However, the exact underlying mechanism of CFE's anti-obesity effects remains unclear. Herein, CFE was orally administered to male C57BL/6 mice for 7 weeks, along with a high-fat diet. CFE (100 mg/kg) effectively induced weight loss, lowered serum cholesterol levels, and suppressed adipocyte differentiation in white adipose tissue (WAT). Furthermore, CFE effectively reduced hepatic total triglyceride, cholesterol, and lipid levels, while significantly improving liver size and color. mRNA expression analysis in WAT and liver tissue revealed that CFE significantly suppressed the expression of PPARγ and aP-2 in adipocyte differentiation, and SREBP-1c and FAS in de novo lipogenesis, suggesting that CFE's anti-obesity effect is exerted by gene inhibition. PRACTICAL APPLICATIONS: Research on marine plants with anti-obesity effects has been increasing recently. This study demonstrated that C. fragile extract (CFE) is effective in reducing body weight and suppressing adipocyte differentiation, along with the improvement of fatty liver in mice fed with a high-fat diet (HFD). The anti-obesity effect of CFE was exhibited by the down-regulation of adipogenesis and lipogenesis, respectively. Based on these results, C. fragile could be useful, not only to effectively combat obesity but also in improving obesity-induced liver dysfunction.

Codium fragile reduces adipose tissue expansion and fatty liver incidence by downregulating adipo- and lipogenesis.

Whole red paprika (Capsicum annuum L.) and its orange-red pigment capsanthin ameliorate obesity-induced skeletal muscle atrophy in mice

The human lifespan has been markedly extended since the 1900s, but it has not brought healthy aging to everyone. This increase in life expectancy without an increase in healthspan is a major global concern that imposes considerable healthcare budgets and degrades the quality of life of older adults. Dietary interventions are a promising strategy to increase healthspan. In this study, we evaluated whether a Gardenia jasminoides Ellis fruit ethanol extract (GFE) increases the lifespan of Caenorhabditis elegans (C. elegans). Treatment with 10 mg/mL GFE increased the lifespan by 27.1% when compared to the vehicle group. GFE (10 mg/mL) treatment improved healthspan-related markers (pharyngeal pumping, muscle quality, age-pigment, and reactive oxygen species accumulation) and exerted a protective effect against amyloid β1-42 toxicity. These effects of GFE are related to the inhibition of insulin/IGF-1 signaling and activation of SKN-1/Nrf, thereby promoting the expression of stress resistance-related genes. In addition, treatment with 10 mM geniposide, the most abundant component of GFE, improved healthspan-related markers and increased lifespan by 18.55% when compared to the vehicle group. Collectively, these findings demonstrate that GFE and its component geniposide increase the lifespan along with healthspan in C. elegans.

Geniposide-rich Gardenia jasminoides Ellis fruit extract increases healthspan in Caenorhabditis elegans.

Longevity through diet restriction and immunity

Age is a risk factor for numerous diseases. Although the development of modern medicine has greatly extended the human lifespan, the duration of relatively healthy old age, or "healthspan," has not increased. Targeting the detrimental processes that can occur before the onset of age-related diseases can greatly improve health and lifespan. Healthspan is significantly affected by what, when, and how much one eats. Dietary restriction, including calorie restriction, fasting, or fasting-mimicking diets, to extend both lifespan and healthspan has recently attracted much attention. However, direct scientific evidence that consuming specific foods extends the lifespan and healthspan seems lacking. Here, we synthesized the results of recent studies on the lifespan and healthspan extension properties of foods and their phytochemicals in various organisms to confirm how far the scientific research on the effect of food on the lifespan has reached.

Chang Hwa Jung

Papers

Codium fragile reduces adipose tissue expansion and fatty liver incidence by downregulating adipo- and lipogenesis.

Whole red paprika (Capsicum annuum L.) and its orange-red pigment capsanthin ameliorate obesity-induced skeletal muscle atrophy in mice

Geniposide-rich Gardenia jasminoides Ellis fruit extract increases healthspan in Caenorhabditis elegans.

Longevity through diet restriction and immunity

Scientific evidence of foods that improve the lifespan and healthspan of different organisms.