bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2024–09–08
fourteen papers selected by
Ayesh Seneviratne, Western University
  1. DNA hydroxymethylation in aging.
  2. Imaging the epigenetic landscape in single cells to study aging trajectories.
  3. Spermidine controls autophagy during fasting.
  4. The planetary health diet is associated with slower cognitive decline - but tied to income.
  5. Older age reduces mtDNA mutation inheritance.
  6. Senolytics target cellular senescence - but can they slow aging?
  7. Age-associated changes in gene regulatory relationships affect basic cellular processes.
  8. Fasting and calorie restriction modulate age-associated immunosenescence and inflammaging.
  9. Experimental TET2 Clonal Hematopoiesis Predisposes to Renal Hypertension Through an Inflammasome-Mediated Mechanism.
  10. ImAge quantitates aging and rejuvenation.
  11. Frailty and Its Implications in Heart Failure with Reduced Ejection Fraction: Impact on Prognosis and Treatment.
  12. Inflamm-ageing: How cytokines and nutrition shape the trajectory of ageing.
  13. Ribosomal S6 kinase 1 regulates inflammaging via the senescence secretome.
  14. Clonal Hematopoiesis Is Associated With Cardiomyopathy During Solid Tumor Therapy.
  1. Nat Aging. 2024 Sep 04.
    DNA hydroxymethylation in aging.
    George Andrew S Inglis.
      
    DOI:  https://doi.org/10.1038/s43587-024-00709-w
  2. Nat Aging. 2024 Aug 29.
    Imaging the epigenetic landscape in single cells to study aging trajectories.
      
    DOI:  https://doi.org/10.1038/s43587-024-00689-x
  3. Nat Aging. 2024 Sep 04.
    Spermidine controls autophagy during fasting.
    Anna Kriebs.
      
    DOI:  https://doi.org/10.1038/s43587-024-00710-3
  4. Nat Aging. 2024 Aug 29.
    The planetary health diet is associated with slower cognitive decline - but tied to income.
      
    DOI:  https://doi.org/10.1038/s43587-024-00705-0
  5. Nat Aging. 2024 Sep 04.
    Older age reduces mtDNA mutation inheritance.
    Polyxeni Papadea, Nils-Göran Larsson.
      
    DOI:  https://doi.org/10.1038/s43587-024-00701-4
  6. Nat Med. 2024 Sep 02.
    Senolytics target cellular senescence - but can they slow aging?
    Natalie Healey.
      
    DOI:  https://doi.org/10.1038/d41591-024-00067-5
  7. Nat Aging. 2024 Sep 03.
    Age-associated changes in gene regulatory relationships affect basic cellular processes.
      
    DOI:  https://doi.org/10.1038/s43587-024-00706-z
  8. Aging Med (Milton). 2024 Aug;7(4): 499-509
    Fasting and calorie restriction modulate age-associated immunosenescence and inflammaging.
    Anteneh Mehari Tizazu.
      Aging is a multifaceted process impacting cells, tissues, organs, and organ systems of the body. Like other systems, aging affects both the adaptive and the innate components of the immune system, a phenomenon known as immunosenescence. The deregulation of the immune system puts elderly individuals at higher risk of infection, lower response to vaccines, and increased incidence of cancer. In the Western world, overnutrition has increased the incidence of obesity (linked with chronic inflammation) which increases the risk of metabolic syndrome, cardiovascular disease, and cancer. Aging is also associated with inflammaging a sterile chronic inflammation that predisposes individuals to age-associated disease. Genetic manipulation of the nutrient-sensing pathway, fasting, and calorie restriction (CR) has been shown to increase the lifespan of model organisms. As well in humans, fasting and CR have also been shown to improve different health parameters. Yet the direct effect of fasting and CR on the aging immune system needs to be further explored. Identifying the effect of fasting and CR on the immune system and how it modulates different parameters of immunosenescence could be important in designing pharmacological or nutritional interventions that slow or revert immunosenescence and strengthen the immune system of elderly individuals. Furthermore, clinical intervention can also be planned, by incorporating fasting or CR with medication, chemotherapy, and vaccination regimes. This review discusses age-associated changes in the immune system and how these changes are modified by fasting and CR which add information on interventions that promote healthy aging and longevity in the growing aging population.
    Keywords:  aging; calorie restriction; fasting; immunosenescence; inflammaging
    DOI:  https://doi.org/10.1002/agm2.12342
  9. Circ Res. 2024 Sep 05.
    Experimental TET2 Clonal Hematopoiesis Predisposes to Renal Hypertension Through an Inflammasome-Mediated Mechanism.
    Ariel H Polizio, Lucila Marino, Kyung-Duk Min, Yoshimitsu Yura, Luca Rolauer, Jesse D Cochran, Megan A Evans, Eunbee Park, Heather Doviak, Emiri Miura-Yura, Miranda E Good, Abigail G Wolpe, Maria Grandoch, Brant Isakson, Kenneth Walsh.
       BACKGROUND: Hypertension incidence increases with age and represents one of the most prevalent risk factors for cardiovascular disease. Clonal events in the hematopoietic system resulting from somatic mutations in driver genes are prevalent in elderly individuals who lack overt hematologic disorders. This condition is referred to as age-related clonal hematopoiesis (CH), and it is a newly recognized risk factor for cardiovascular disease. It is not known whether CH and hypertension in the elderly are causally related and, if so, what are the mechanistic features.
    METHODS AND RESULTS: A murine model of adoptive bone marrow transplantation was employed to examine the interplay between Tet2 (ten-eleven translocation methylcytosine dioxygenase 2) CH and hypertension. In this model, a subpressor dose of Ang II (angiotensin II) resulted in elevated systolic and diastolic blood pressure as early as 1 day after the challenge. These conditions led to the expansion of Tet2-deficient proinflammatory monocytes and bone marrow progenitor populations. Tet2-deficiency promoted renal CCL5 chemokine expression and macrophage infiltration into the kidney. Consistent with macrophage involvement, Tet2-deficiency in myeloid cells promoted hypertension when mice were treated with a subpressor dose of Ang II. The hematopoietic Tet2-/- condition led to sodium retention, renal inflammasome activation, and elevated levels of IL (interleukin)-1β and IL-18. Analysis of the sodium transporters indicated NCC (Na+-Cl- cotransporter) and NKCC2 activation at residues Thr53 and Ser105, respectively. Administration of the NLRP3 inflammasome inhibitor MCC950 reversed the hypertensive state, sodium retention, and renal transporter activation.
    CONCLUSIONS: Tet2-mediated CH sensitizes mice to a hypertensive stimulus. Mechanistically, the expansion of hematopoietic Tet2-deficient cells promotes hypertension due to elevated renal immune cell infiltration and activation of the NLRP3 inflammasome, with consequences on sodium retention. These data indicate that carriers of TET2 CH could be at elevated risk for the development of hypertension and that immune modulators could be useful in treating hypertension in this patient population.
    Keywords:  clonal hematopoiesis; hypertension; inflammation; kidney; sodium homeostasis
    DOI:  https://doi.org/10.1161/CIRCRESAHA.124.324492
  10. Nat Aging. 2024 Aug 29.
    ImAge quantitates aging and rejuvenation.
    Martin Alvarez-Kuglen, Kenta Ninomiya, Haodong Qin, Delany Rodriguez, Lorenzo Fiengo, Chen Farhy, Wei-Mien Hsu, Brian Kirk, Aaron Havas, Gen-Sheng Feng, Amanda J Roberts, Rozalyn M Anderson, Manuel Serrano, Peter D Adams, Tatyana O Sharpee, Alexey V Terskikh.
      For efficient, cost-effective and personalized healthcare, biomarkers that capture aspects of functional, biological aging, thus predicting disease risk and lifespan more accurately and reliably than chronological age, are essential. We developed an imaging-based chromatin and epigenetic age (ImAge) that captures intrinsic age-related trajectories of the spatial organization of chromatin and epigenetic marks in single nuclei, in mice. We show that such trajectories readily emerge as principal changes in each individual dataset without regression on chronological age, and that ImAge can be computed using several epigenetic marks and DNA labeling. We find that interventions known to affect biological aging induce corresponding effects on ImAge, including increased ImAge upon chemotherapy treatment and decreased ImAge upon caloric restriction and partial reprogramming by transient OSKM expression in liver and skeletal muscle. Further, ImAge readouts from chronologically identical mice inversely correlated with their locomotor activity, suggesting that ImAge may capture elements of biological and functional age. In sum, we developed ImAge, an imaging-based biomarker of aging with single-cell resolution rooted in the analysis of spatial organization of epigenetic marks.
    DOI:  https://doi.org/10.1038/s43587-024-00685-1
  11. Heart Fail Clin. 2024 Oct;pii: S1551-7136(24)00047-3. [Epub ahead of print]20(4): 387-398
    Frailty and Its Implications in Heart Failure with Reduced Ejection Fraction: Impact on Prognosis and Treatment.
    Khawaja M Talha, Stephen J Greene, Javed Butler, Muhammad Shahzeb Khan.
      Frailty affects half of all patients with heart failure with reduced ejection fraction (HFrEF) and carries a ∼2-fold increased risk of mortality. The relationship between frailty and HFrEF is bidirectional, with one condition exacerbating the other. Paradoxical to their higher clinical risk, frail patients with HFrEF are more often under-treated due to concerns over medication-related adverse clinical events. However, current evidence suggests consistent safety of HF medical therapies among older frail patients with HFrEF. A multidisciplinary effort is necessary for the appropriate management of these high-risk patients which focuses on the optimization of known beneficial therapies with a goal-directed effort toward improving quality of life.
    Keywords:  Frailty; Guideline-directed medical therapy; Heart failure; Mortality; Reduced ejection fraction; Rehabilitation
    DOI:  https://doi.org/10.1016/j.hfc.2024.06.005
  12. Cytokine Growth Factor Rev. 2024 Sep 02. pii: S1359-6101(24)00065-0. [Epub ahead of print]
    Inflamm-ageing: How cytokines and nutrition shape the trajectory of ageing.
    Francesca Coperchini, Alessia Greco, Marsida Teliti, Laura Croce, Spyridon Chytiris, Flavia Magri, Carlo Gaetano, Mario Rotondi.
      Population ageing is increasing in prevalence in most developed countries. Ageing is the decline of functional properties at the cellular, tissue, and organ level. Biochemical changes that occur in all organisms that experience biological ageing are referred to as the "Hallmarks of ageing". Inflammation is a common denominator of the hallmarks of ageing, being mechanistically involved in most age-related health consequences. Inflamm-ageing refers to age-related changes in the inflammatory and immune systems which somehow drive the ageing process towards healthy or unhealthy ageing. Current evidences, support that, reversing the age-related pro-inflammatory status of inflamm-ageing, is able to modulate most hallmarks of ageing. Inflamm-ageing is associated with increased levels of pro-inflammatory molecules (e.g. cytokines, chemokines), ultimately producing a chronic low-grade inflammatory state typically observed in older individuals. It is commonly accepted that, the balance between pro- and anti-inflammatory cytokines/chemokines is one of the factors determining whether healthy or unhealthy ageing occurs. Malnutrition and nutritional imbalances, are highly prevalent in the elderly, playing a role in driving the balance of pro- and anti-inflammatory immunoactive molecules. In particular, malnutrition is a major risk factor for sarcopenia, a phenomenon characterized by loss of muscle mass, which is often referred to as the biological basis for frailty. Given the close relationship between malnutrition and sarcopenia, there is also evidence for a link between malnutrition and frailty. Indeed, changes in cytokine/chemokine levels in elderly patients with malnutrition were demonstrated. The demonstration that specific cytokines play a role in modulating appetite and nutrient sensing and taste reception, provided further evidence for the existence of a link between inflamm-ageing, nutrition and cytokines in shaping the trajectory of ageing. The present review will overview current evidence supporting the role of specific circulating cytokines and chemokines in the relationship between ageing, inflammation, and malnutrition.
    Keywords:  Ageing; Chemokines; Cytokines; Elderly; Inflammation; Malnutrition
    DOI:  https://doi.org/10.1016/j.cytogfr.2024.08.004
  13. Nat Aging. 2024 Aug 29.
    Ribosomal S6 kinase 1 regulates inflammaging via the senescence secretome.
    Suchira Gallage, Elaine E Irvine, Jose Efren Barragan Avila, Virinder Reen, Silvia M A Pedroni, Imanol Duran, Vikas Ranvir, Sanjay Khadayate, Joaquim Pombo, Sharon Brookes, Danijela Heide, Gopuraja Dharmalingham, Agharul I Choudhury, Indrabahadur Singh, Nicolás Herranz, Santiago Vernia, Mathias Heikenwalder, Jesús Gil, Dominic J Withers.
      Inhibition of S6 kinase 1 (S6K1) extends lifespan and improves healthspan in mice, but the underlying mechanisms are unclear. Cellular senescence is a stable growth arrest accompanied by an inflammatory senescence-associated secretory phenotype (SASP). Cellular senescence and SASP-mediated chronic inflammation contribute to age-related pathology, but the specific role of S6K1 has not been determined. Here we show that S6K1 deletion does not reduce senescence but ameliorates inflammation in aged mouse livers. Using human and mouse models of senescence, we demonstrate that reduced inflammation is a liver-intrinsic effect associated with S6K deletion. Specifically, we show that S6K1 deletion results in reduced IRF3 activation; impaired production of cytokines, such as IL1β; and reduced immune infiltration. Using either liver-specific or myeloid-specific S6K knockout mice, we also demonstrate that reduced immune infiltration and clearance of senescent cells is a hepatocyte-intrinsic phenomenon. Overall, deletion of S6K reduces inflammation in the liver, suggesting that suppression of the inflammatory SASP by loss of S6K could underlie the beneficial effects of inhibiting this pathway on healthspan and lifespan.
    DOI:  https://doi.org/10.1038/s43587-024-00695-z
  14. JACC CardioOncol. 2024 Aug;6(4): 605-607
    Clonal Hematopoiesis Is Associated With Cardiomyopathy During Solid Tumor Therapy.
    Etienne Leveille, Rachel Jaber Cheheyeb, Carlos Matute-Martinez, Nathan W Chen, Ritujith Jayakrishnan, Anthos Christofides, Derrick Lin, Yunju Im, Giulia Biancon, Jennifer VanOudenhove, Stephanie Halene, Jennifer M Kwan.
      
    DOI:  https://doi.org/10.1016/j.jaccao.2024.05.013
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