bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2022–06–19
six papers selected by
Ayesh Seneviratne, Western University
  1. Does diet influence aging? Evidence from animal studies.
  2. The Inflamm-Aging Model Identifies Key Risk Factors in Atherosclerosis.
  3. Clonal hematopoiesis in clinical practice: walking a tightrope.
  4. Regulation of the lysosome by sphingolipids: potential role in aging.
  5. Adherence to Low-Fat, Vegan Diets in Individuals With Type 2 Diabetes: A Review.
  6. CRISPR screening in cancer stem cells.
  1. J Intern Med. 2022 Jun 14.
    Does diet influence aging? Evidence from animal studies.
    David G Le Couteur, David Raubenheimer, Samantha Solon-Biet, Rafael de Cabo, Stephen J Simpson.
      Nutrition profoundly influences the risk for many age-related diseases. Whether nutrition influences human aging biology directly is less clear. Studies in different animal species indicate that reducing food intake ('caloric restriction', CR) can increase lifespan and delay the onset of diseases and the biological hallmarks of aging. Obesity has been described as 'accelerated aging' and therefore the lifespan and health benefits generated by CR in both aging and obesity may occur via similar mechanisms. Beyond calorie intake, studies based on nutritional geometry have shown that protein intake and the interaction between dietary protein and carbohydrates influence age-related health and lifespan. Studies where animals are caloric restricted by providing free access to diluted diets have had less impact on lifespan than those studies where animals are given a reduced aliquot of food each day and are fasting between meals. This has drawn attention to the role of fasting in health and aging, and exploration of the health effects of various fasting regimes. Although definitive human clinical trials of nutrition and aging would need to be unfeasibly long and unrealistically controlled, there is good evidence from animal experiments that some nutritional interventions based on CR, manipulating dietary macronutrients and fasting can influence aging biology and lifespan. This article is protected by copyright. All rights reserved.
    Keywords:  aging; caloric restriction; fasting; nutritional geometry; obesity
    DOI:  https://doi.org/10.1111/joim.13530
  2. Front Genet. 2022 ;13 865827
    The Inflamm-Aging Model Identifies Key Risk Factors in Atherosclerosis.
    Yudan He, Yao Chen, Lilin Yao, Junyi Wang, Xianzheng Sha, Yin Wang.
      Background: Atherosclerosis, one of the main threats to human life and health, is driven by abnormal inflammation (i.e., chronic inflammation or oxidative stress) during accelerated aging. Many studies have shown that inflamm-aging exerts a significant impact on the occurrence of atherosclerosis, particularly by inducing an immune homeostasis imbalance. However, the potential mechanism by which inflamm-aging induces atherosclerosis needs to be studied more thoroughly, and there is currently a lack of powerful prediction models. Methods: First, an improved inflamm-aging prediction model was constructed by integrating aging, inflammation, and disease markers with the help of machine learning methods; then, inflamm-aging scores were calculated. In addition, the causal relationship between aging and disease was identified using Mendelian randomization. A series of risk factors were also identified by causal analysis, sensitivity analysis, and network analysis. Results: Our results revealed an accelerated inflamm-aging pattern in atherosclerosis and suggested a causal relationship between inflamm-aging and atherosclerosis. Mechanisms involving inflammation, nutritional balance, vascular homeostasis, and oxidative stress were found to be driving factors of atherosclerosis in the context of inflamm-aging. Conclusion: In summary, we developed a model integrating crucial risk factors in inflamm-aging and atherosclerosis. Our computation pipeline could be used to explore potential mechanisms of related diseases.
    Keywords:  atherosclerosis; causal analysis; immune homeostasis; inflamm-aging; sensitive analysis
    DOI:  https://doi.org/10.3389/fgene.2022.865827
  3. Leuk Lymphoma. 2022 Jun 13. 1-9
    Clonal hematopoiesis in clinical practice: walking a tightrope.
    Francesco Tarantini, Cosimo Cumbo, Luisa Anelli, Antonella Zagaria, Nicoletta Coccaro, Giuseppina Tota, Giorgina Specchia, Pellegrino Musto, Francesco Albano.
      The understanding of clonal hematopoiesis (CH) and its features is rapidly evolving in step with the spread of sequencing techniques. Indeed, CH detection is now an emerging aspect in clinical practice. The awareness of CH intersects with consolidated diagnostic paths, thus exposing 'grey zone' circumstances under the magnifying lens of clinicians. The interpretation of genomic data poses, in some cases, a true clinical challenge, sometimes further complicating the route to diagnosis. The line separating different entities is thin. The present work aims to review some of these challenging situations to help clinicians keep their balance along this tightrope.
    Keywords:  Clonal hematopoiesis; MRD; cytopenia; double-mutated MPN; oligomonocytic-CMML; splenomegaly
    DOI:  https://doi.org/10.1080/10428194.2022.2087068
  4. J Biol Chem. 2022 Jun 09. pii: S0021-9258(22)00559-2. [Epub ahead of print] 102118
    Regulation of the lysosome by sphingolipids: potential role in aging.
    Haiqing Tang, Xiaokun Huang, Shanshan Pang.
      Sphingolipids are a class of bioactive complex lipids that have been closely associated with aging and aging-related diseases. However, the mechanism through which sphingolipids control aging has long been a mystery. Emerging studies reveal that sphingolipids exert tight control over lysosomal homeostasis and function, as evidenced by sphingolipid-related diseases, including but not limited to lysosomal storage disorders. These diseases are defined by primary lysosomal defects and a few secondary defects such as mitochondrial dysfunction. Intriguingly, recent research indicates that the majority of these defects are also associated with aging, implying that sphingolipid-related diseases and aging may share common mechanisms. We propose that the lysosome is a pivotal hub for sphingolipid-mediated aging regulation. This review discusses the critical roles of sphingolipid metabolism in regulating various lysosomal functions, with an emphasis on how such regulation may contribute to aging and aging-related diseases.
    Keywords:  aging; lifespan; lysosomal calcium; lysosomal cell death; lysosome; lysosome-mitochondria communication; mTOR; sphingolipid
    DOI:  https://doi.org/10.1016/j.jbc.2022.102118
  5. Am J Lifestyle Med. 2022 May-Jun;16(3):16(3): 300-310
    Adherence to Low-Fat, Vegan Diets in Individuals With Type 2 Diabetes: A Review.
    Maximilian Andreas Storz.
      Low-fat, vegan diets seem to be particularly effective for glycemic control and may significantly lower hemoglobin A1c levels in individuals with type 2 diabetes. However, health care providers report low levels of practice and argue that this diet is hard to follow. This controversy on the acceptability of low-fat vegan diets appears to be a significant barrier to its broader clinical implementation. This review investigated dropout and adherence rates in intervention studies using a low-fat vegan diet in individuals with type 2 diabetes. In contrast to the common belief that this diet is poorly accepted, this review suggests different findings. Dietary adherence appears to be good with approximately 50% of individuals meeting the criteria for high adherence in most studies. Adherence to a low-fat vegan diet was higher than adherence to conventional diets in several studies. Group support and regular supervision improve adherence. Moreover, relatively low dropout rates were found-indirectly indicating good acceptance and high patient interest in this particular dietary modification. Although this review has several important limitations, it appears inappropriate to associate low-fat, vegan diets with poor adherence in individuals with type 2 diabetes. With good and regular support, adherence rates are more than solid and physicians should advocate for this diet more frequently.
    Keywords:  acceptance; adherence; dropout rate; low-fat; nutrition therapy; type 2 diabetes; vegan
    DOI:  https://doi.org/10.1177/1559827620964755
  6. Essays Biochem. 2022 Jun 17. pii: EBC20220009. [Epub ahead of print]
    CRISPR screening in cancer stem cells.
    Bei Wang, Alan S L Wong.
      Cancer stem cells (CSCs) are a subpopulation of tumor cells with self-renewal ability. Increasing evidence points to the critical roles of CSCs in tumorigenesis, metastasis, therapy resistance, and cancer relapse. As such, the elimination of CSCs improves cancer treatment outcomes. However, challenges remain due to limited understanding of the molecular mechanisms governing self-renewal and survival of CSCs. Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screening has been increasingly used to identify genetic determinants in cancers. In this primer, we discuss the progress made and emerging opportunities of coupling advanced CRISPR screening systems with CSC models to reveal the understudied vulnerabilities of CSCs.
    Keywords:  CRISPR; Cancer stem cells; high-throughput screening
    DOI:  https://doi.org/10.1042/EBC20220009
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