bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2022–07–31
four papers selected by
Ayesh Seneviratne, Western University



  1. Signal Transduct Target Ther. 2022 07 23. 7(1): 252
      Nutriments have been deemed to impact all physiopathologic processes. Recent evidences in molecular medicine and clinical trials have demonstrated that adequate nutrition treatments are the golden criterion for extending healthspan and delaying ageing in various species such as yeast, drosophila, rodent, primate and human. It emerges to develop the precision-nutrition therapeutics to slow age-related biological processes and treat diverse diseases. However, the nutritive advantages frequently diversify among individuals as well as organs and tissues, which brings challenges in this field. In this review, we summarize the different forms of dietary interventions extensively prescribed for healthspan improvement and disease treatment in pre-clinical or clinical. We discuss the nutrient-mediated mechanisms including metabolic regulators, nutritive metabolism pathways, epigenetic mechanisms and circadian clocks. Comparably, we describe diet-responsive effectors by which dietary interventions influence the endocrinic, immunological, microbial and neural states responsible for improving health and preventing multiple diseases in humans. Furthermore, we expatiate diverse patterns of dietotheroapies, including different fasting, calorie-restricted diet, ketogenic diet, high-fibre diet, plants-based diet, protein restriction diet or diet with specific reduction in amino acids or microelements, potentially affecting the health and morbid states. Altogether, we emphasize the profound nutritional therapy, and highlight the crosstalk among explored mechanisms and critical factors to develop individualized therapeutic approaches and predictors.
    DOI:  https://doi.org/10.1038/s41392-022-01104-w
  2. Cell Rep. 2022 Jul 26. pii: S2211-1247(22)00907-X. [Epub ahead of print]40(4): 111105
      A functional electron transport chain (ETC) is crucial for supporting bioenergetics and biosynthesis. Accordingly, ETC inhibition decreases proliferation in cancer cells but does not seem to impair stem cell proliferation. However, it remains unclear how stem cells metabolically adapt. In this study, we show that pharmacological inhibition of complex III of the ETC in skeletal stem and progenitor cells induces glycolysis side pathways and reroutes the tricarboxylic acid (TCA) cycle to regenerate NAD+ and preserve cell proliferation. These metabolic changes also culminate in increased succinate and 2-hydroxyglutarate levels that inhibit Ten-eleven translocation (TET) DNA demethylase activity, thereby preserving self-renewal and multilineage potential. Mechanistically, mitochondrial malate dehydrogenase and reverse succinate dehydrogenase activity proved to be essential for the metabolic rewiring in response to ETC inhibition. Together, these data show that the metabolic plasticity of skeletal stem and progenitor cells allows them to bypass ETC blockade and preserve their self-renewal.
    Keywords:  CP: Metabolism; CP: Stem cell research; NAD regeneration; TCA rerouting; TET activity; cell-based regenerative medicine; electron transport chain; metabolic plasticity; proliferation; reverse succinate dehydrogenase; self-renewal; skeletal stem cells
    DOI:  https://doi.org/10.1016/j.celrep.2022.111105
  3. Nat Rev Immunol. 2022 Jul 25.
      Numerous mitochondrial constituents and metabolic products can function as damage-associated molecular patterns (DAMPs) and promote inflammation when released into the cytosol or extracellular milieu. Several safeguards are normally in place to prevent mitochondria from eliciting detrimental inflammatory reactions, including the autophagic disposal of permeabilized mitochondria. However, when the homeostatic capacity of such systems is exceeded or when such systems are defective, inflammatory reactions elicited by mitochondria can become pathogenic and contribute to the aetiology of human disorders linked to autoreactivity. In addition, inefficient inflammatory pathways induced by mitochondrial DAMPs can be pathogenic as they enable the establishment or progression of infectious and neoplastic disorders. Here we discuss the molecular mechanisms through which mitochondria control inflammatory responses, the cellular pathways that are in place to control mitochondria-driven inflammation and the pathological consequences of dysregulated inflammatory reactions elicited by mitochondrial DAMPs.
    DOI:  https://doi.org/10.1038/s41577-022-00760-x
  4. Nutrients. 2022 Jul 22. pii: 3012. [Epub ahead of print]14(15):
      No organism can avoid the process of aging, which is often accompanied by chronic disease. The process of biological aging is driven by a series of interrelated mechanisms through different signal pathways, including oxidative stress, inflammatory states, autophagy and others. In addition, the intestinal microbiota play a key role in regulating oxidative stress of microglia, maintaining homeostasis of microglia and alleviating age-related diseases. Tea polyphenols can effectively regulate the composition of the intestinal microbiota. In recent years, the potential anti-aging benefits of tea polyphenols have attracted increasing attention because they can inhibit neuroinflammation and prevent degenerative effects in the brain. The interaction between human neurological function and the gut microbiota suggests that intervention with tea polyphenols is a possible way to alleviate brain-aging. Studies have been undertaken into the possible mechanisms underpinning the preventative effect of tea polyphenols on brain-aging mediated by the intestinal microbiota. Tea polyphenols may be regarded as potential neuroprotective substances which can act with high efficiency and low toxicity.
    Keywords:  anti-aging; intestinal microbiota; microglia; neurological diseases; tea polyphenols
    DOI:  https://doi.org/10.3390/nu14153012