bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2023–07–02
fiveteen papers selected by
Ayesh Seneviratne, Western University
  1. Impact of Geroscience on Therapeutic Strategies for Older Adults With Cardiovascular Disease: JACC Scientific Statement.
  2. Hunger modulates aging in Drosophila.
  3. Mitochondrial fitness sustains healthy muscle aging.
  4. Increasing Our Understanding of How Dietary Components Can Affect Cellular Mechanisms That Regulate Aging and Slow the Onset of Frailty and Chronic Diseases.
  5. The meaning of adaptation in aging: insights from cellular senescence, epigenetic clocks and stem cell alterations.
  6. Research progress on aging mechanism and drugs and the role of stem cells in anti-aging process.
  7. Myeloproliferative neoplasms - blurring the lines between cancer and chronic inflammatory disorder.
  8. Acyl coenzyme A binding protein (ACBP): An aging- and disease-relevant "autophagy checkpoint".
  9. Beyond Ozempic: brand-new obesity drugs will be cheaper and more effective.
  10. The plasticity of fibroblasts: A forgotten player in the aging process.
  11. Dietary restriction mitigates the age-associated decline in mouse B cell receptor repertoire diversity.
  12. Vitamin K and Hallmarks of Ageing: Focus on Diet and Gut Microbiome.
  13. Caloric restriction and fasting-mimicking diets in the treatment of cancer patients.
  14. Ageing in the brain: mechanisms and rejuvenating strategies.
  15. Benefit of the Reduced Dose Combination of Azacitidine and Venetoclax in an Elderly Patient With Acute Myeloid Leukemia.
  1. J Am Coll Cardiol. 2023 Jun 21. pii: S0735-1097(23)05782-0. [Epub ahead of print]
    Impact of Geroscience on Therapeutic Strategies for Older Adults With Cardiovascular Disease: JACC Scientific Statement.
    Daniel E Forman, George A Kuchel, John C Newman, James L Kirkland, Elena Volpi, George E Taffet, Nir Barzilai, Ambarish Pandey, Dalane W Kitzman, Peter Libby, Luigi Ferrucci.
      Geroscience posits that cardiovascular disease (CVD) and other chronic diseases result from progressive erosion of the effectiveness of homeostatic mechanisms that oppose age-related accumulation of molecular damage. This hypothetical common root to chronic diseases explains why patients with CVD are often affected by multimorbidity and frailty and why older age negatively affects CVD prognosis and treatment response. Gerotherapeutics enhance resilience mechanisms that counter age-related molecular damage to prevent chronic diseases, frailty, and disability, thereby extending healthspan. Here, we describe the main resilience mechanisms of mammalian aging, with a focus on how they can affect CVD pathophysiology. We next present novel gerotherapeutic approaches, some of which are already used in management of CVD, and explore their potential to transform care and management of CVD. The geroscience paradigm is gaining traction broadly in medical specialties, with potential to mitigate premature aging, reduce health care disparities, and improve population healthspan.
    Keywords:  frailty; geroscience; hallmarks; inflammation; multimorbidity
    DOI:  https://doi.org/10.1016/j.jacc.2023.05.038
  2. Lab Anim (NY). 2023 Jul;52(7): 142
    Hunger modulates aging in Drosophila.
    Alexandra Le Bras.
      
    DOI:  https://doi.org/10.1038/s41684-023-01204-2
  3. Aging (Albany NY). 2023 Jun 24. 15
    Mitochondrial fitness sustains healthy muscle aging.
    Andrea Irazoki, Antonio Zorzano, David Sebastián.
      
    Keywords:  aging; mitochondria; mitochondrial dynamics; mitophagy; sarcopenia
    DOI:  https://doi.org/10.18632/aging.204857
  4. Nutrients. 2023 Jun 09. pii: 2687. [Epub ahead of print]15(12):
    Increasing Our Understanding of How Dietary Components Can Affect Cellular Mechanisms That Regulate Aging and Slow the Onset of Frailty and Chronic Diseases.
    Cristiano Capurso.
      The current average life expectancy at birth is well over 80 years [...].
    DOI:  https://doi.org/10.3390/nu15122687
  5. Nat Aging. 2023 Jun 29.
    The meaning of adaptation in aging: insights from cellular senescence, epigenetic clocks and stem cell alterations.
    Mikolaj Ogrodnik, Vadim N Gladyshev.
      With recent rapid progress in research on aging, there is increasing evidence that many features commonly considered to be mechanisms or drivers of aging in fact represent adaptations. Here, we examine several such features, including cellular senescence, epigenetic aging and stem cell alterations. We draw a distinction between the causes and consequences of aging and define short-term consequences as 'responses' and long-term ones as 'adaptations'. We also discuss 'damaging adaptations', which despite having beneficial effects in the short term, lead to exacerbation of the initial insult and acceleration of aging. Features commonly recognized as 'basic mechanisms of the aging process' are critically examined for the possibility of their adaptation-driven emergence from processes such as cell competition and the wound-like features of the aging body. Finally, we speculate on the meaning of these interactions for the aging process and their relevance for the development of antiaging interventions.
    DOI:  https://doi.org/10.1038/s43587-023-00447-5
  6. Exp Gerontol. 2023 Jun 28. pii: S0531-5565(23)00169-9. [Epub ahead of print] 112248
    Research progress on aging mechanism and drugs and the role of stem cells in anti-aging process.
    Yuxuan Zhang, Qingjuan Li, Yuhu Niu, Kaixin Wei, Xiuwei Wang, Bo Niu, Li Zhang.
      There have been many discussions on longevity from ancient times to the present day. In the Laozi, it is said, "Heaven and earth are long and enduring because they do not arise from themselves, so they can live forever." In Zhuangzi - Zai You, it is also said, "Keep your mental peace, and your body will be healthy. Don't strain your body and don't consume your spirit to live a long life." It is clear that people attach importance to anti-aging and the desire for longevity. Throughout human history, we have treated aging as an inevitable process, but with the development of medical science, we have become more aware of the various molecular changes in the human body. In an aging society, more people are suffering from age-related diseases such as osteoporosis, Alzheimer's disease, and cardiovascular disease, which has led to a search for anti-aging. However, by 'living longer' we mean not only living but also living longer in good health. The mechanisms of aging are still unclear and there is a great deal of interest and curiosity in how to combat aging effectively. Some potential criteria exist for the determination of anti-aging drugs: the first criterion is the ability to exert life-extending effects in model organisms, preferably in mammals; the second criterion is the ability to prevent or delay several age-related diseases in mammals; and the third criterion is the ability to inhibit the transition of cells from a quiescent to a senescent state. Based on these criteria, the current anti-aging drugs often involved are rapamycin, metformin, curcumin and other polyphenols, polysaccharides, resveratrol, etc. The most studied and relatively well-understood pathways and factors of aging are currently known to include seven enzymes, six biological factors, and one chemical, which mainly involve more than ten pathways such as Nrf2/SKN-1; NFκB; AMPK; P13K/AKT; IGF; and NAD.
    Keywords:  Agine mechanisms; Aging; Anti-aging drugs; Stem cells
    DOI:  https://doi.org/10.1016/j.exger.2023.112248
  7. Front Oncol. 2023 ;13 1208089
    Myeloproliferative neoplasms - blurring the lines between cancer and chronic inflammatory disorder.
    Eli M Soyfer, Angela G Fleischman.
      Myeloproliferative Neoplasm (MPN) is a group of chronic blood cancers that arise from a hematopoietic stem cell (HSC) clone with somatic mutations causing constitutive activation of myeloid cytokine receptor signaling. In addition to elevated blood cell counts, MPN typically presents with increased inflammatory signaling and inflammation symptoms. Therefore, while being a clonally derived neoplasm, MPN has much in common with chronic non-cancerous inflammatory conditions, such as rheumatoid arthritis, lupus, and many more. MPN and chronic inflammatory disease (CID) share similar chronicity, symptoms, dependency on the immune system, environmental triggers, and treatments. Overall, we will highlight the similarities between an MPN and CID. We highlight that while MPN is classified as a cancer, its behavior is more aligned to that of a chronic inflammatory disease. We propose that MPN should inhabit a fluid/spectrum between auto-inflammatory disease and cancer.
    Keywords:  autoimmunity; clonal hematopoiesis; cytokines; inflammation; myeloproliferative neoplasm
    DOI:  https://doi.org/10.3389/fonc.2023.1208089
  8. Aging Cell. 2023 Jun 26. e13910
    Acyl coenzyme A binding protein (ACBP): An aging- and disease-relevant "autophagy checkpoint".
    Léa Montégut, Mahmoud Abdellatif, Omar Motiño, Frank Madeo, Isabelle Martins, Victor Quesada, Carlos López-Otín, Guido Kroemer.
      Acyl coenzyme A binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), is a phylogenetically ancient protein present in some eubacteria and the entire eukaryotic radiation. In several eukaryotic phyla, ACBP/DBI transcends its intracellular function in fatty acid metabolism because it can be released into the extracellular space. This ACBP/DBI secretion usually occurs in response to nutrient scarcity through an autophagy-dependent pathway. ACBP/DBI and its peptide fragments then act on a range of distinct receptors that diverge among phyla, namely metabotropic G protein-coupled receptor in yeast (and likely in the mammalian central nervous system), a histidine receptor kinase in slime molds, and ionotropic gamma-aminobutyric acid (GABA)A receptors in mammals. Genetic or antibody-mediated inhibition of ACBP/DBI orthologs interferes with nutrient stress-induced adaptations such as sporulation or increased food intake in multiple species, as it enhances lifespan or healthspan in yeast, plant leaves, nematodes, and multiple mouse models. These lifespan and healthspan-extending effects of ACBP/DBI suppression are coupled to the induction of autophagy. Altogether, it appears that neutralization of extracellular ACBP/DBI results in "autophagy checkpoint inhibition" to unleash the anti-aging potential of autophagy. Of note, in humans, ACBP/DBI levels increase in various tissues, as well as in the plasma, in the context of aging, obesity, uncontrolled infection or cardiovascular, inflammatory, neurodegenerative, and malignant diseases.
    Keywords:  aging; autophagy; diazepam-binding inhibitor; endozepin; evolution; metabolism
    DOI:  https://doi.org/10.1111/acel.13910
  9. Nature. 2023 Jun 26.
    Beyond Ozempic: brand-new obesity drugs will be cheaper and more effective.
    Saima Sidik.
      
    Keywords:  Diabetes; Medical research; Metabolism; Obesity
    DOI:  https://doi.org/10.1038/d41586-023-02092-9
  10. Ageing Res Rev. 2023 Jun 28. pii: S1568-1637(23)00154-X. [Epub ahead of print] 101995
    The plasticity of fibroblasts: A forgotten player in the aging process.
    Antero Salminen.
      Tissue-resident fibroblasts are mesenchymal cells which possess an impressive plasticity in their ability to modify their properties according to the requirements of the microenvironment. There are diverse subgroups of fibroblast phenotypes associated with different tissue pathological conditions, e.g., cancers, wound healing, and many fibrotic and inflammatory conditions. The heterogeneous phenotypes can be subdivided into fibrogenic and non-fibrogenic, inflammatory and immunosuppressive subtypes as well as cellular senescent subsets. A major hallmark of activated fibroblasts is that they contain different amounts of stress fibers combined with α-smooth muscle actin (α-SMA) protein, i.e., commonly this phenotype has been called the myofibroblast. Interestingly, several stresses associated with the aging process are potent inducers of myofibroblast differentiation, e.g., oxidative and endoplasmic reticulum stresses, extracellular matrix (ECM) disorders, inflammatory mediators, and telomere shortening. Accordingly, anti-aging treatments with metformin and rapamycin inhibited the differentiation of myofibroblasts in tissues. There is evidence that the senescent phenotype induced in cultured fibroblasts does not represent the phenotype of fibroblasts in aged tissues. Considering the versatile plasticity of fibroblasts as well as their frequency and structural importance in tissues, it does seem that fibroblasts are overlooked players in the aging process.
    Keywords:  Ageing; Fibroaging; Fibrosis; Immunosuppression; Inflammaging
    DOI:  https://doi.org/10.1016/j.arr.2023.101995
  11. Cell Rep. 2023 Jun 28. pii: S2211-1247(23)00733-7. [Epub ahead of print]42(7): 112722
    Dietary restriction mitigates the age-associated decline in mouse B cell receptor repertoire diversity.
    Carolina Monzó, Lisonia Gkioni, Andreas Beyer, Dario Riccardo Valenzano, Sebastian Grönke, Linda Partridge.
      Aging impairs the capacity to respond to novel antigens, reducing immune protection against pathogens and vaccine efficacy. Dietary restriction (DR) extends life- and health span in diverse animals. However, little is known about the capacity of DR to combat the decline in immune function. Here, we study the changes in B cell receptor (BCR) repertoire during aging in DR and control mice. By sequencing the variable region of the BCR heavy chain in the spleen, we show that DR preserves diversity and attenuates the increase in clonal expansions throughout aging. Remarkably, mice starting DR in mid-life have repertoire diversity and clonal expansion rates indistinguishable from chronic DR mice. In contrast, in the intestine, these traits are unaffected by either age or DR. Reduced within-individual B cell repertoire diversity and increased clonal expansions are correlated with higher morbidity, suggesting a potential contribution of B cell repertoire dynamics to health during aging.
    Keywords:  B cell receptor repertoire; CP: Immunology; adaptive immunity; aging; dietary restriction; late onset; mice
    DOI:  https://doi.org/10.1016/j.celrep.2023.112722
  12. Nutrients. 2023 Jun 12. pii: 2727. [Epub ahead of print]15(12):
    Vitamin K and Hallmarks of Ageing: Focus on Diet and Gut Microbiome.
    Lu Dai, Denise Mafra, Paul G Shiels, Tilman M Hackeng, Peter Stenvinkel, Leon J Schurgers.
      Vitamin K and vitamin K-dependent proteins have been reported to be associated with a large spectrum of age-related diseases. While most of these associations have been deduced from observational studies, solid evidence for the direct impact of vitamin K on cellular senescence remains to be proven. As vitamin K status reflects the complexity of interactions between dietary intake, gut microbiome activity and health, we will demonstrate the pivotal role of the diet-microbiome-health axis in human ageing and exemplify how vitamin K is implicated therein. We propose that food quality (i.e., food pattern) should be highlighted beyond the quantity of total vitamin K intake. Instead of focusing on a single nutrient, exploring a healthy diet containing vitamin K may be more strategic. As such, healthy eating patterns can be used to make dietary recommendations for the public. Emerging evidence suggests that dietary vitamin K is a modulator of the diet-microbiome-health axis, and this needs to be incorporated into the investigation of the impact of vitamin K on gut microbial composition and metabolic activities, along with host health outcomes. In addition, we highlight several critical caveats that need to be acknowledged regarding the interplay between diet, vitamin K, gut microbiome and host health that is pivotal for elucidating the role of vitamin K in ageing and responding to the urgent call of healthy eating concerning public health.
    Keywords:  ageing; food pattern; gut microbiome; vitamin K
    DOI:  https://doi.org/10.3390/nu15122727
  13. Curr Opin Clin Nutr Metab Care. 2023 Jun 20.
    Caloric restriction and fasting-mimicking diets in the treatment of cancer patients.
    Jann Arends.
       PURPOSE OF REVIEW: Different forms of caloric restriction for patients with cancer are widely advertised in lay circles, based mainly on promising preclinical experiments, while evidence from clinical trials is still preliminary. This review aims to present physiological responses to fasting and update knowledge on recently accumulated evidence from preclinical models and clinical trials.
    RECENT FINDINGS: Like other mild stressors, caloric restriction induces hormetic changes in healthy cells, which increase the tolerance to subsequent more severe stressors. While protecting healthy tissues, caloric restriction sensitizes malignant cells to toxic interventions because of their deficiencies in hormetic mechanisms, especially control of autophagy. In addition, caloric restriction may activate anticancer-directed immune cells and deactivate suppressive cells, thus increasing immunosurveillance and anticancer cytotoxicity. These effects may combine to increase the effectivity of cancer treatments while limiting adverse events. Though evidence obtained from preclinical models is promising, clinical trials in cancer patients so far have been preliminary. In clinical trials it will remain essential to avoid inducing or aggravating malnutrition.
    SUMMARY: Based on physiology and evidence from preclinical models, caloric restriction is a promising candidate as a potential combination partner for clinical anticancer treatment. However, large randomized clinical trials investigating effects on clinical outcome in patients with cancer are still lacking.
    DOI:  https://doi.org/10.1097/MCO.0000000000000959
  14. Cell Mol Life Sci. 2023 Jun 24. 80(7): 190
    Ageing in the brain: mechanisms and rejuvenating strategies.
    Filipa Gaspar-Silva, Diogo Trigo, Joana Magalhaes.
      Ageing is characterized by the progressive loss of cellular homeostasis, leading to an overall decline of the organism's fitness. In the brain, ageing is highly associated with cognitive decline and neurodegenerative diseases. With the rise in life expectancy, characterizing the brain ageing process becomes fundamental for developing therapeutic interventions against the increased incidence of age-related neurodegenerative diseases and to aim for an increase in human life span and, more importantly, health span. In this review, we start by introducing the molecular/cellular hallmarks associated with brain ageing and their impact on brain cell populations. Subsequently, we assess emerging evidence on how systemic ageing translates into brain ageing. Finally, we revisit the mainstream and the novel rejuvenating strategies, discussing the most successful ones in delaying brain ageing and related diseases.
    Keywords:  Ageing; Brain; Cognition; Neurodegeneration; Rejuvenation
    DOI:  https://doi.org/10.1007/s00018-023-04832-6
  15. Cureus. 2023 May;15(5): e39481
    Benefit of the Reduced Dose Combination of Azacitidine and Venetoclax in an Elderly Patient With Acute Myeloid Leukemia.
    Keita Fujino, Hiroshi Ureshino, Tetsumi Yoshida, Tatsuo Ichinohe.
      Elderly patients with acute myeloid leukemia (AML) have been found to clinically benefit from the combination of azacitidine (AZA) and venetoclax (VEN), although the safety and efficacy of the treatment in extremely elderly patients (age >85 years) have not been fully established. An 88-year-old woman diagnosed with AML was given a lower dose of AZA and VEN. She eventually developed grade 4 hypokalemia, necessitating treatment interruption. However, a lower dose of VEN was successfully continued in the subsequent cycle of treatment, resulting in complete remission. Hence, reduced AZA and VEN doses may be beneficial for extremely elderly AML patients.
    Keywords:  acute myeloid leukemia (aml); azacitidine; bcl-2; elderly population; venetoclax
    DOI:  https://doi.org/10.7759/cureus.39481
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