bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2023‒06‒25
eight papers selected by
Ayesh Seneviratne
Western University
  1. Chronic Inflammation and the Hallmarks of Aging.
  2. By the numbers: China's changing diet.
  3. Genotoxic aldehyde stress prematurely ages hematopoietic stem cells in a p53-driven manner.
  4. "Diet for the prevention and management of sarcopenia".
  5. Prevalence and risk factors of frailty among older family caregivers.
  6. Sarcopenia, osteoporosis and frailty.
  7. Failed in aging? Queering in living with dementia.
  8. Cardio-oncology and transplantation for acute myeloid leukemia.
  1. Mol Metab. 2023 Jun 15. pii: S2212-8778(23)00089-3. [Epub ahead of print] 101755
    Chronic Inflammation and the Hallmarks of Aging.
    Jordan J Baechle, Nan Chen, Priya Makhijani, Shawn Winer, David Furman, Daniel A Winer.
      BACKGROUND: Recently, the hallmarks of aging were updated to include dysbiosis, disabled macroautophagy, and chronic inflammation. In particular, the low-grade chronic inflammation during aging, without overt infection, is defined as "inflammaging," which is associated with increased morbidity and mortality in the aging population. Emerging evidence suggests a bidirectional and cyclical relationship between chronic inflammation and the development of age-related conditions, such as cardiovascular diseases, neurodegeneration, cancer, and frailty. How the crosstalk between chronic inflammation and other hallmarks of aging underlies biological mechanisms of aging and age-related disease is thus of particular interest to the current geroscience research.SCOPE OF REVIEW: This review integrates the cellular and molecular mechanisms of age-associated chronic inflammation with the other eleven hallmarks of aging. Extra discussion is dedicated to the hallmark of "altered nutrient sensing," given the scope of Molecular Metabolism. The deregulation of hallmark processes during aging disrupts the delicate balance between pro-inflammatory and anti-inflammatory signaling, leading to a persistent inflammatory state. The resultant chronic inflammation, in turn, further aggravates the dysfunction of each hallmark, thereby driving the progression of aging and age-related diseases.
    MAIN CONCLUSIONS: The crosstalk between chronic inflammation and other hallmarks of aging results in a vicious cycle that exacerbates the decline in cellular functions and promotes aging. Understanding this complex interplay will provide new insights into the mechanisms of aging and the development of potential anti-aging interventions. Given their interconnectedness and ability to accentuate the primary elements of aging, drivers of chronic inflammation may be an ideal target with high translational potential to address the pathological conditions associated with aging.
    DOI:  https://doi.org/10.1016/j.molmet.2023.101755
  2. Nature. 2023 Jun 22.
    By the numbers: China's changing diet.
    Yvaine Ye, Jack Leeming.
      
    Keywords:  Economics; Nutrition; Obesity
    DOI:  https://doi.org/10.1038/d41586-023-02060-3
  3. Mol Cell. 2023 Jun 15. pii: S1097-2765(23)00419-7. [Epub ahead of print]
    Genotoxic aldehyde stress prematurely ages hematopoietic stem cells in a p53-driven manner.
    Meng Wang, Laura T L Brandt, Xiaonan Wang, Holly Russell, Emily Mitchell, Ashley N Kamimae-Lanning, Jill M Brown, Felix A Dingler, Juan I Garaycoechea, Tomoya Isobe, Sarah J Kinston, Muxin Gu, George S Vassiliou, Nicola K Wilson, Berthold Göttgens, Ketan J Patel.
      Aged hematopoietic stem cells (HSCs) display diminished self-renewal and a myeloid differentiation bias. However, the drivers and mechanisms that underpin this fundamental switch are not understood. HSCs produce genotoxic formaldehyde that requires protection by the detoxification enzymes ALDH2 and ADH5 and the Fanconi anemia (FA) DNA repair pathway. We find that the HSCs in young Aldh2-/-Fancd2-/- mice harbor a transcriptomic signature equivalent to aged wild-type HSCs, along with increased epigenetic age, telomere attrition, and myeloid-biased differentiation quantified by single HSC transplantation. In addition, the p53 response is vigorously activated in Aldh2-/-Fancd2-/- HSCs, while p53 deletion rescued this aged HSC phenotype. To further define the origins of the myeloid differentiation bias, we use a GFP genetic reporter to find a striking enrichment of Vwf+ myeloid and megakaryocyte-lineage-biased HSCs. These results indicate that metabolism-derived formaldehyde-DNA damage stimulates the p53 response in HSCs to drive accelerated aging.
    Keywords:  DNA damage; DNA-damage response; aging; aldehydes; hematopoiesis; myeloid bias; p53
    DOI:  https://doi.org/10.1016/j.molcel.2023.05.035
  4. Metabolism. 2023 Jun 21. pii: S0026-0495(23)00241-X. [Epub ahead of print] 155637
    "Diet for the prevention and management of sarcopenia".
    Riccardo Calvani, Anna Picca, Hélio José Coelho-Júnior, Matteo Tosato, Emanuele Marzetti, Francesco Landi.
      Sarcopenia is a geriatric condition characterized by a progressive loss of skeletal muscle mass and strength, with an increased risk of adverse health outcomes (e.g., falls, disability, institutionalization, reduced quality of life, mortality). Pharmacological remedies are currently unavailable for preventing the development of sarcopenia, halting its progression, or impeding its negative health outcomes. The most effective strategies to contrast sarcopenia rely on the adoption of healthier lifestyle behaviors, including adherence to high-quality diets and regular physical activity. In this review, the role of nutrition in the prevention and management of sarcopenia is summarized. Special attention is given to current "blockbuster" dietary regimes and agents used to counteract age-related muscle wasting, together with their putative mechanisms of action. Issues related to the design and implementation of effective nutritional strategies are discussed, with a focus on unanswered questions on the most appropriate timing of nutritional interventions to preserve muscle health and function into old age. A brief description is also provided on new technologies that can facilitate the development and implementation of personalized nutrition plans to contrast sarcopenia.
    Keywords:  Handgrip strength; Mediterranean diet; Muscle mass; Nutrition; Physical function; Protein
    DOI:  https://doi.org/10.1016/j.metabol.2023.155637
  5. Scand J Caring Sci. 2023 Jun 21.
    Prevalence and risk factors of frailty among older family caregivers.
    Outi Kiljunen, Tarja Välimäki, Roosa-Maria Savela, Sohvi Koponen, Irma Nykänen, Anna Liisa Suominen, Ursula Schwab.
      AIM: The aim of this study was to investigate the prevalence of frailty and identify the demographical and clinical factors associated with frailty among older family caregivers.METHOD: The participants of this cross-sectional study were older family caregivers (n = 125) living in Eastern Finland. Data on functional and cognitive status, depressive symptoms, nutritional status, medication, chronic diseases, stroke, and oral health were obtained. The Mini Nutritional Assessment (MNA) was used to evaluate nutritional status. Frailty status was evaluated using the abbreviated comprehensive geriatric assessment (aCGA) scale.
    RESULTS: Seventy-three percent of caregivers were identified as frail. According to multivariable logistic regression, cataract, glaucoma, or macular degeneration and the MNA score were predictors of frailty. After adjusting for age, gender, and number of own teeth, the MNA score remained a significant predictor of frailty (adjusted OR = 1.22, 95% CI = 1.06, 1.41). As the MNA scores decreased (meaning poorer nutritional status), the risk of frailty increased.
    CONCLUSIONS: The present study showed that frailty is prevalent among older family caregivers. Recognising older family caregivers with frailty or at risk of frailty is vital. It is essential to acknowledge vision problems' role in frailty and to monitor and support the nutritional status of family caregivers regularly to prevent frailty development.
    Keywords:  aCGA; family caregivers; frailty; informal caregivers; older adults; older people
    DOI:  https://doi.org/10.1111/scs.13190
  6. Metabolism. 2023 Jun 20. pii: S0026-0495(23)00242-1. [Epub ahead of print] 155638
    Sarcopenia, osteoporosis and frailty.
    Evelien Gielen, Jolan Dupont, Marian Dejaeger, Michaël R Laurent.
      Muscles and bones are intricately connected tissues displaying marked co-variation during development, growth, aging, and in many diseases. While the diagnosis and treatment of osteoporosis are well established in clinical practice, sarcopenia has only been classified internationally as a disease in 2016. Both conditions are associated with an increased risk of adverse health outcomes such as fractures, dysmobility and mortality. Rather than focusing on one dimension of bone or muscle mass or weakness, the concept of musculoskeletal frailty captures the overall loss of physiological reserves in the locomotor system with age. The term osteosarcopenia in particular refers to the double jeopardy of osteoporosis and sarcopenia. Muscle-bone interactions at the biomechanical, cellular, paracrine, endocrine, neuronal or nutritional level may contribute to the pathophysiology of osteosarcopenia. The paradigm wherein muscle force controls bone strength is increasingly facing competition from a model centering on the exchange of myokines, osteokines and adipokines. The most promising results have been obtained in preclinical models where common drug targets have been identified to treat these conditions simultaneously. In this narrative review, we critically summarize the current understanding of the definitions, epidemiology, pathophysiology, and treatment of osteosarcopenia as part of an integrative approach to musculoskeletal frailty.
    Keywords:  Bone; Frailty; Muscle; Older adults; Osteoporosis; Sarcopenia
    DOI:  https://doi.org/10.1016/j.metabol.2023.155638
  7. Front Sociol. 2023 ;8 1139271
    Failed in aging? Queering in living with dementia.
    Valerie Keller.
      This article explored the ways in which living with dementia brings potentials to queer the concept of "successful aging" and associated notions of being human. Regarding the progressive development of dementia, it can be assumed that people affected, no matter how hard they try, will sooner or later fail to age successfully. They increasingly become a symbol of what is called the "fourth age" and are framed as an essentialized other. Based on statements of people with dementia, it will be examined to what extent the position on the outside enables people affected to abandon societal guiding ideals and undermine hegemonic-dominant notions of aging. It is shown how they develop life-affirming ways of being-in-the-world that run counter to the idea of the rational, autonomous, consistent, active, productive, and healthy human beings.
    Keywords:  age; aging; dementia; failing; ideals; norms; queering; self-care
    DOI:  https://doi.org/10.3389/fsoc.2023.1139271
  8. Best Pract Res Clin Haematol. 2023 Jun;pii: S1521-6926(23)00026-9. [Epub ahead of print]36(2): 101465
    Cardio-oncology and transplantation for acute myeloid leukemia.
    Jai Singh.
      Despite the rapidly evolving treatment landscape for acute myeloid leukemia (AML), allogeneic hematopoietic cell transplantation (allo-HCT) remains an important and potentially curative treatment option for many high-risk AML patients. Cardiovascular disease is an important competing risk throughout allo-HCT and a key driver of morbidity and mortality long after treatment. Cardio-oncology is a new discipline in cardiology which provides multidisciplinary care and expertise to complex cancer patients with the aims of optimizing cardiovascular health plus monitoring and treating potential cardiotoxicity related to cancer treatments. As allogeneic HCT techniques get more sophisticated there will be an increase in transplant eligible older patients with a rise in comorbidities including established cardiovascular disease highlighting the need for close collaboration with cardio-oncology specialists from the time of diagnosis through late survivorship.
    Keywords:  Acute myeloid leukemia; Allogeneic hematopoietic cell transplantation; Cardio-oncology; Cardiotoxicity
    DOI:  https://doi.org/10.1016/j.beha.2023.101465
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