bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2023–10–01
fiveteen papers selected by
Ayesh Seneviratne, Western University
  1. Co-designing to enable modern aging.
  2. Aging-disturbed FUS Phase Transition Impairs Hematopoietic Stem Cell by Altering Chromatin Structure.
  3. New Possibilities for Evaluating the Development of Age-Related Pathologies Using the Dynamical Network Biomarkers Theory.
  4. The anti-aging mechanism of ginsenosides with medicine and food homology.
  5. Rejuvenation of Senescent Mesenchymal Stem Cells to Prevent Age-Related Changes in Synovial Joints.
  6. Frailty and Its Implications in Heart Failure with Reduced Ejection Fraction: Impact on Prognosis and Treatment.
  7. Elucidating and Expanding the Restorative Theory Framework to Comprehend Influential Factors Supporting Ageing-in-Place: A Scoping Review.
  8. Twenty-five years of aging research and innovation in the Living Lab.
  9. Anti-inflammatory effect of interleukin-6 highly enriched in secretome of two clinically relevant sources of mesenchymal stromal cells.
  10. Serum SIRT6 Levels Are Associated with Frailty in Older Adults.
  11. Effect of Mediterranean Dietary Pattern on Cognitive Status in Community-Dwelling Older Adults.
  12. Spreading Senescent Cells' Burden and Emerging Therapeutic Targets for Frailty.
  13. The brain cells linked to protection against dementia.
  14. Editorial: Neuroinflammation in the interaction between aging and chronic brain injury.
  15. The Role of Mitochondrial Dysfunction in Idiopathic Pulmonary Fibrosis: New Perspectives for a Challenging Disease.
  1. Nat Aging. 2023 Sep 28.
    Co-designing to enable modern aging.
    Global Centre for Modern Ageing (GCMA)
      
    DOI:  https://doi.org/10.1038/s43587-023-00494-y
  2. Blood. 2023 Sep 25. pii: blood.2023020539. [Epub ahead of print]
    Aging-disturbed FUS Phase Transition Impairs Hematopoietic Stem Cell by Altering Chromatin Structure.
    Baixue Tang, Xinming Wang, Hanqing He, Ruiqing Chen, Guofeng Qiao, Yang Yang, Zihan Xu, Longteng Wang, Qiongye Dong, Jia Yu, Michael Zhang, Minglei Shi, Jianwei Wang.
      Aged hematopoietic stem cells (HSCs) exhibit compromised reconstitution capacity. While, the molecular mechanisms behind this phenomenon are not fully understood. In this study, we observed that the expression of FUS is increased in aged HSCs and enforced FUS recapitulates the phenotype of aged HSCs through RGG-mediated aberrant FUS phase transition. By utilizing Fus-gfp mice, we observed that FUShigh HSCs exhibit compromised FUS mobility and resemble aged HSCs both functionally and transcriptionally. The percentage of FUShigh HSCs is increased upon physiological aging and replication stress, and FUSlow HSCs of aged mice exhibit youthful function. Mechanistically, FUShigh HSCs exhibit a different global chromatin organization compared to FUSlow HSCs, which is observed in aged HSCs. A large number of TADs are merged in aged HSCs due to the compromised binding of CTCF with chromatin, which is invoked by aberrant FUS condensates. It is notable that the transcriptional alteration between FUShigh and FUSlow HSCs originates from the merged TADs and are enriched in HSC aging-related genes. Collectively, this study for the first time reveals that aberrant FUS mobility promotes HSC aging by altering chromatin structure.
    DOI:  https://doi.org/10.1182/blood.2023020539
  3. Cells. 2023 09 17. pii: 2297. [Epub ahead of print]12(18):
    New Possibilities for Evaluating the Development of Age-Related Pathologies Using the Dynamical Network Biomarkers Theory.
    Kazutaka Akagi, Keiichi Koizumi, Makoto Kadowaki, Isao Kitajima, Shigeru Saito.
      Aging is the slowest process in a living organism. During this process, mortality rate increases exponentially due to the accumulation of damage at the cellular level. Cellular senescence is a well-established hallmark of aging, as well as a promising target for preventing aging and age-related diseases. However, mapping the senescent cells in tissues is extremely challenging, as their low abundance, lack of specific markers, and variability arise from heterogeneity. Hence, methodologies for identifying or predicting the development of senescent cells are necessary for achieving healthy aging. A new wave of bioinformatic methodologies based on mathematics/physics theories have been proposed to be applied to aging biology, which is altering the way we approach our understand of aging. Here, we discuss the dynamical network biomarkers (DNB) theory, which allows for the prediction of state transition in complex systems such as living organisms, as well as usage of Raman spectroscopy that offers a non-invasive and label-free imaging, and provide a perspective on potential applications for the study of aging.
    Keywords:  Raman spectroscopy; aging; dynamical network biomarkers theory; resilience
    DOI:  https://doi.org/10.3390/cells12182297
  4. Food Funct. 2023 Sep 28.
    The anti-aging mechanism of ginsenosides with medicine and food homology.
    Tiantian Tian, Chung-Nga Ko, Wenya Luo, Dan Li, Chao Yang.
      With the acceleration of global aging and the rise in living standards, the achievement of healthy aging is becoming an imperative issue globally. Ginseng, a medicinal plant that has a long history of dietary intake and remarkable medicinal value, has become a research hotspot in the field of food and medicine. Ginsenosides, especially protopanaxadiol-type saponins and protopanaxatriol-type saponins, are among the most important active ingredients in ginseng. Ginsenosides have been found to exhibit powerful and diverse pharmacological activities, such as antiaging, antitumor, antifatigue and immunity enhancement activities. Their effects in antiaging mainly include (1) promotion of metabolism and stem cell proliferation, (2) protection of skin and nerves, (3) modulation of intestinal flora, (4) maintenance of mitochondrial function, and (5) enhancement of telomerase activity. The underlying mechanisms are primarily associated with the intervention of the signaling pathways in apoptosis, inflammation and oxidative stress. In this review, the mechanism of action of ginsenosides in antiaging as well as the potential values of developing ginsenoside-based functional foods and antiaging drugs are discussed.
    DOI:  https://doi.org/10.1039/d3fo02580b
  5. Cell Transplant. 2023 Jan-Dec;32:32 9636897231200065
    Rejuvenation of Senescent Mesenchymal Stem Cells to Prevent Age-Related Changes in Synovial Joints.
    Tatiana Sekelova, Lubos Danisovic, Michaela Cehakova.
      Mesenchymal/medicinal stem/signaling cells (MSCs), well known for regenerative potential, have been involved in hundreds of clinical trials. Even if equipped with reparative properties, aging significantly decreases their biological activity, representing a major challenge for MSC-based therapies. Age-related joint diseases, such as osteoarthritis, are associated with the accumulation of senescent cells, including synovial MSCs. An impaired ability of MSCs to self-renew and differentiate is one of the main contributors to the human aging process. Moreover, senescent MSCs (sMSCs) are characterized by the senescence-messaging secretome (SMS), which is typically manifested by the release of molecules with an adverse effect. Many factors, from genetic and metabolic pathways to environmental stressors, participate in the regulation of the senescent phenotype of MSCs. To better understand cellular senescence in MSCs, this review discusses the characteristics of sMSCs, their role in cartilage and synovial joint aging, and current rejuvenation approaches to delay/reverse age-related pathological changes, providing evidence from in vivo experiments as well.
    Keywords:  aging joint; rejuvenation; senescence; senescence-messaging secretome; senescent mesenchymal/medicinal stem/signaling cells
    DOI:  https://doi.org/10.1177/09636897231200065
  6. Cardiol Clin. 2023 Nov;pii: S0733-8651(23)00058-9. [Epub ahead of print]41(4): 525-536
    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.ccl.2023.06.002
  7. Int J Environ Res Public Health. 2023 09 21. pii: 6801. [Epub ahead of print]20(18):
    Elucidating and Expanding the Restorative Theory Framework to Comprehend Influential Factors Supporting Ageing-in-Place: A Scoping Review.
    Anne Johanna Jacoba Grave, Louis Neven, Masi Mohammadi.
      Exposure to stress and attention fatigue resulting from changes in capabilities and residing in environments that do not align with individual needs can adversely impact older adults' mental health and complicate ageing-in-place. Research into the psychological restoration process can help assist in alleviating these issues. Existing research on restoration perspectives has predominantly centred on university students and lacks comprehensive insights into older adults. Consequently, this study seeks to acquire a deeper understanding of the restorative theory framework within the context of ageing populations. We identified and analysed thirty-nine papers on the restoration process of older adults employing the scoping review method. Our findings indicate that adjustments to the general restorative theory framework are imperative for ageing populations. By incorporating additional features-such as being with and familiarity-the framework can more effectively support the development of age-inclusive neighbourhoods that enhance the mental health of the older population and facilitate healthy ageing-in-place. While more in-depth research is required on the restoration process of older adults, this research marks the initial in adapting the general framework to ageing populations. Furthermore, insight is given into how the adapted framework can contribute to help address the challenges of global ageing and support ageing-in-place.
    Keywords:  ageing-in-place; mental health; older adults; psychological restoration; restorative environments
    DOI:  https://doi.org/10.3390/ijerph20186801
  8. Nat Aging. 2023 Sep 28.
    Twenty-five years of aging research and innovation in the Living Lab.
    Hilde Verbeek, Judith Urlings, Jan Hamers.
      
    DOI:  https://doi.org/10.1038/s43587-023-00482-2
  9. Front Cell Dev Biol. 2023 ;11 1244120
    Anti-inflammatory effect of interleukin-6 highly enriched in secretome of two clinically relevant sources of mesenchymal stromal cells.
    Marianne Dedier, Brice Magne, Muriel Nivet, Sébastien Banzet, Marina Trouillas.
      Despite several advances in the field of regenerative medicine, clinical management of extensive skin wounds or burns remains a major therapeutic issue. During the past few years, Mesenchymal Stromal Cells (MSCs) have emerged as a novel therapeutic tool to promote tissue repair through their anti-inflammatory, pro-trophic and pro-remodeling effects. They exert their biological activity mainly via the secretion of soluble bioactive molecules such as cytokines, growth factors, proteins and microRNAs which can be encapsulated within extracellular vesicles (EV). The recent discovery of their high plasticity to external stimuli has fostered the development of new targeted therapies known as priming strategies, to enhance their potential. Our team recently showed that Interleukin-1β (IL-1β)-primed gingival MSCs promote wound healing and epidermal engraftment in vitro, and in vivo through their secreted products that contain extracellular vesicles. In the present work, we investigated whether two common sources of MSCs, gingiva and bone marrow, could respond similarly to IL-1β to favor pro-healing capabilities of their secretome. We showed that both primed-MSC sources, or their related secreted products, are able to reduce inflammation in LPS-challenged human monocytic THP-1 cell line. IL-1β priming enhanced MSC secretion of wound healing-related growth factors, cytokines and miRNAs in both sources. Among them, interleukin 6 was shown to be involved in the anti-inflammatory effect of MSC secreted products. Overall, these results underline the pro-healing properties of both MSC sources and their secretome upon IL-1β priming and their potential to improve the current medical treatment of severe wounds.
    Keywords:  extracellular vesicles; interleurkin-6; mesenchymal stromal cells; priming; secretome; wound healing
    DOI:  https://doi.org/10.3389/fcell.2023.1244120
  10. J Nutr Health Aging. 2023 ;27(9): 719-725
    Serum SIRT6 Levels Are Associated with Frailty in Older Adults.
    M Zhu, X Yang, Y Huang, Z Wang, Z Xiong.
       OBJECTIVES: Frailty is one of the major health problems facing aging societies worldwide. We investigated the association between serum SIRT6 and frailty in older adults.
    DESIGN: Cross-sectional analysis of associations of serum SIRT6 and frailty in older people.
    SETTING: Enrolled community-dwelling and hospital outpatient clinic adults older than 65 years old in Wuhan City, Hubei Province, China.
    PARTICIPANTS: A total of 540 community-dwelling older adults (age ≥ 65 years) in Wuhan were included in the study.
    MEASURES: We used Frailty Phenotype criteria for classifying participants based on their frailty status. Serum SIRT6 was measured using an ELISA kit.
    RESULTS: A total of 540 older adults were included in this cross-sectional study. Serum SIRT6 was lower in the slowness group (7.23±1.81 vs 5.89±1.74, p<0.001), weakness group (6.87±1.88 vs 5.68±1.64, p<0.001), and exhaustion group (6.73±1.90 vs 5.88±1.74, p<0.001) compare with the normal group. ROC curves were used to assess the efficiency of SIRT6 in predicting frailty in older adults. The AUC for SIRT6 was 0.792 (95% CI: 0.7514 to 0.8325), with the highest sensitivity of 68.0% and the specificity of 91.9%, and the optimal critical value of 4.65ng/ml according to Youden's index. Multivariate logistic regression analysis showed that serum SIRT6 level was independently associated with frailty in older people.
    CONCLUSION: In conclusion, serum SIRT6 was decreased in frailty compared with robust older adults. A decreased serum SIRT6 was independently associated with an increased risk of frailty. SIRT6 may be a potential target for the treatment of patients with frailty.
    Keywords:  Aging ; frailty; serum SIRT6
    DOI:  https://doi.org/10.1007/s12603-023-1969-y
  11. Nutrients. 2023 Sep 08. pii: 3911. [Epub ahead of print]15(18):
    Effect of Mediterranean Dietary Pattern on Cognitive Status in Community-Dwelling Older Adults.
    Nathalie Yaghi, Rita El Hayeck, Christa Boulos, Marianne Abifadel, César Yaghi.
      Modifiable factors associated with cognitive decline (CD) require more attention, particularly dietary patterns. This study aimed to investigate the link between cognitive decline and associated factors, particularly dietary patterns (DPs), in community-dwelling older Lebanese of modest economic status. Our cross-sectional national study included 352 participants above 60 years old, from the medico-social centers of the ministry of social affairs all over the country. CD was screened based on literacy. Nutritional and dietary data were collected through a validated food frequency questionnaire. DPs were extracted by the K-mean cluster analysis. CD was found in 32.7% and 61.5% of literate and illiterate groups, respectively. Identified DPs included a Westernized type and Mediterranean type, with high and moderate food intakes. In the context of literacy, independent factors associated with CD were age above 80 years, living in Beirut, frailty, and adopting a Westernized (OR = 3.08, 95% CI: 1.22-7.8) and a high-intake Mediterranean DP (OR = 2.11, 95% CI: 1.05-4.22). In the context of illiteracy, the same factors were associated with CD, but not DP nor frailty, with an age cut-off at 78 years. In a Lebanese sample of older adults, factors associated with CD depend on the level of literacy, with DP only associated with CD in the context of literacy.
    Keywords:  Mediterranean country; Mediterranean diet; Westernized diet; aging; cognitive decline; cognitive impairment; dietary pattern; older adults
    DOI:  https://doi.org/10.3390/nu15183911
  12. Cells. 2023 09 15. pii: 2287. [Epub ahead of print]12(18):
    Spreading Senescent Cells' Burden and Emerging Therapeutic Targets for Frailty.
    Serena Marcozzi, Giorgia Bigossi, Maria Elisa Giuliani, Giovanni Lai, Robertina Giacconi, Francesco Piacenza, Marco Malavolta.
      The spreading of senescent cells' burden holds profound implications for frailty, prompting the exploration of novel therapeutic targets. In this perspective review, we delve into the intricate mechanisms underlying senescent cell spreading, its implications for frailty, and its therapeutic development. We have focused our attention on the emerging age-related biological factors, such as microbiome and virome alterations, elucidating their significant contribution to the loss of control over the accumulation rate of senescent cells, particularly affecting key frailty domains, the musculoskeletal system and cerebral functions. We believe that gaining an understanding of these mechanisms could not only aid in elucidating the involvement of cellular senescence in frailty but also offer diverse therapeutic possibilities, potentially advancing the future development of tailored interventions for these highly diverse patients.
    Keywords:  aging; cellular senescence; frailty; immunosenescence; microbiome; virome
    DOI:  https://doi.org/10.3390/cells12182287
  13. Nature. 2023 Sep 28.
    The brain cells linked to protection against dementia.
    Sara Reardon.
      
    Keywords:  Ageing; Alzheimer's disease; Brain; Neurodegeneration
    DOI:  https://doi.org/10.1038/d41586-023-03012-7
  14. Front Aging Neurosci. 2023 ;15 1283438
    Editorial: Neuroinflammation in the interaction between aging and chronic brain injury.
    Xintong Ge.
      
    Keywords:  aging; chronic brain injury; cognitive; neurodegeneration; neuroinflammation
    DOI:  https://doi.org/10.3389/fnagi.2023.1283438
  15. Biology (Basel). 2023 Sep 14. pii: 1237. [Epub ahead of print]12(9):
    The Role of Mitochondrial Dysfunction in Idiopathic Pulmonary Fibrosis: New Perspectives for a Challenging Disease.
    Juan David Cala-Garcia, German Jose Medina-Rincon, Paula Andrea Sierra-Salas, Julio Rojano, Freddy Romero.
      Mitochondrial biology has always been a relevant field in chronic diseases such as fibrosis or cancer in different organs of the human body, not to mention the strong association between mitochondrial dysfunction and aging. With the development of new technologies and the emergence of new methodologies in the last few years, the role of mitochondria in pulmonary chronic diseases such as idiopathic pulmonary fibrosis (IPF) has taken an important position in the field. With this review, we will highlight the latest advances in mitochondrial research on pulmonary fibrosis, focusing on the role of the mitochondria in the aging lung, new proposals for mechanisms that support mitochondrial dysfunction as an important cause for IPF, mitochondrial dysfunction in different cell populations of the lung, and new proposals for treatment of the disease.
    Keywords:  mitochondria; mitochondrial biogenesis; mitochondrial dysfunction; mitophagy; pulmonary fibrosis
    DOI:  https://doi.org/10.3390/biology12091237
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