bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2023‒01‒29
thirteen papers selected by
Ayesh Seneviratne
Western University

  1. Eur J Cell Biol. 2023 Jan 20. pii: S0171-9335(23)00004-3. [Epub ahead of print]102(2): 151289
      Organismal aging is impacted by the deterioration of tissue turnover mechanisms due, in part, to the decline in stem cell function. This decline can be related to mitochondrial dysfunction and underlying energetic defects that, in concert, help drive biological aging. Thus, mitochondria have been described as a potential interventional target to hinder the loss of stem cell robustness, and subsequently, decrease tissue turnover decline and age-associated pathologies. In this review, we focused our analysis on the most recent literature on mitochondria and stem cell aging and discuss the potential benefits of targeting mitochondria in preventing stem cell dysfunction and thus influencing aging.
    Keywords:  Aging; Mesenchymal stem cell; Mitochondria
  2. Front Cell Dev Biol. 2022 ;10 1095235
    Keywords:  adipose tissue; aging; cancer; inflammation; metabolism; mitochondria; obesity; stem cells
  3. Life Med. 2022 Oct;1(2): 103-119
      Aging is a natural but relentless process of physiological decline, leading to physical frailty, reduced ability to respond to physical stresses (resilience) and, ultimately, organismal death. Cellular senescence, a self-defensive mechanism activated in response to intrinsic stimuli and/or exogenous stress, is one of the central hallmarks of aging. Senescent cells cease to proliferate, while remaining metabolically active and secreting numerous extracellular factors, a feature known as the senescence-associated secretory phenotype. Senescence is physiologically important for embryonic development, tissue repair, and wound healing, and prevents carcinogenesis. However, chronic accumulation of persisting senescent cells contributes to a host of pathologies including age-related morbidities. By paracrine and endocrine mechanisms, senescent cells can induce inflammation locally and systemically, thereby causing tissue dysfunction, and organ degeneration. Agents including those targeting damaging components of the senescence-associated secretory phenotype or inducing apoptosis of senescent cells exhibit remarkable benefits in both preclinical models and early clinical trials for geriatric conditions. Here we summarize features of senescent cells and outline strategies holding the potential to be developed as clinical interventions. In the long run, there is an increasing demand for safe, effective, and clinically translatable senotherapeutics to address healthcare needs in current settings of global aging.
    Keywords:  aging; clinical trial; senescence-associated secretory phenotype; senescent cell; senotherapeutics
  4. Front Med (Lausanne). 2022 ;9 1027055
      Introduction: Calorie restriction (CR) is an important direction for the delay of sarcopenia in elderly individuals. However, the specific mechanisms of CR against aging are still unclear.Methods: In this study, we used a CR model of elderly mice with muscle-specific 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) knockout mice and 11β-HSD1 overexpression mice to confirm that CR can delay muscle aging by inhibiting 11β-HSD1 which can transform inactive GC(cortisone) into active GC(cortisol). The ability of self-proliferation and differentiation into muscle fibers of these mouse muscle stem cells (MuSCs) was observed in vitro. Additionally, the mitochondrial function and mitochondrial ATP production capacity of MuSCs were measured by mitochondrial oxygen consumption.
    Results: It was found that the 11β-HSD1 expression level was increased in age-related muscle atrophy. Overexpression of 11β-HSD1 led to muscle atrophy in young mice, and 11β-HSD1 knockout rescued age-related muscle atrophy. Moreover, CR in aged mice reduced the local effective concentration of glucocorticoid (GC) through 11β-HSD1, thereby promoting the mitochondrial function and differentiation ability of MuSCs.
    Conclusions: Together, our findings highlight promising sarcopenia protection with 40% CR in older ages. Furthermore, we speculated that targeting an 11β-HSD1-dependent metabolic pathway may represent a novel strategy for developing therapeutics against age-related muscle atrophy.
    Keywords:  11β-HSD1; caloric restriction (CR); mitochondrial function; muscle atrophy; muscle stem cells (MuSCs)
  5. Nature. 2023 Jan 27.
    Keywords:  Health care; Infection; Public health; Vaccines
  6. Front Neurosci. 2022 ;16 1039379
      Mental health and neurodevelopmental disorders are extremely common across the lifespan and are characterized by a complicated range of symptoms that affect wellbeing. There are relatively few drugs available that target disease mechanisms for any of these disorders. Instead, therapeutics are focused on symptoms and syndromes, largely driven by neurotransmitter hypotheses, such as serotonin or dopamine hypotheses of depression. Emerging evidence suggests that maternal inflammation during pregnancy plays a key role in neurodevelopmental disorders, and inflammation can influence mental health expression across the lifespan. It is now recognized that commonly used psychiatric drugs (anti-depressants, anti-psychotics, and mood stabilizers) have anti-inflammatory properties. In this review, we bring together the human evidence regarding the anti-inflammatory mechanisms for these main classes of psychiatric drugs across a broad range of mental health disorders. All three classes of drugs showed evidence of decreasing levels of pro-inflammatory cytokines, particularly IL-6 and TNF-α, while increasing the levels of the anti-inflammatory cytokine, IL-10. Some studies also showed evidence of reduced inflammatory signaling via nuclear factor- (NF-)κB and signal transducer and activator of transcription (STAT) pathways. As researchers, clinicians, and patients become increasingly aware of the role of inflammation in brain health, it is reassuring that these psychiatric drugs may also abrogate this inflammation, in addition to their effects on neurotransmission. Further studies are required to determine whether inflammation is a driver of disease pathogenesis, and therefore should be a therapeutic target in future clinical trials.
    Keywords:  anti-depressants; anti-psychotics; inflammation; mental health; mood stabilizers
  7. Geroscience. 2023 Jan 27.
      We investigated efficient representations of binarized health deficit data using the 2001-2002 National Health and Nutrition Examination Survey (NHANES). We compared the abilities of features to compress health deficit data and to predict adverse outcomes. We used principal component analysis (PCA) and several other dimensionality reduction techniques, together with several varieties of the frailty index (FI). We observed that the FI approximates the first - primary - component obtained by PCA and other compression techniques. Most adverse outcomes were well predicted using only the FI. While the FI is therefore a useful technique for compressing binary deficits into a single variable, additional dimensions were needed for high-fidelity compression of health deficit data. Moreover, some outcomes - including inflammation and metabolic dysfunction - showed high-dimensional behaviour. We generally found that clinical data were easier to compress than lab data. Our results help to explain the success of the FI as a simple dimensionality reduction technique for binary health data. We demonstrate how PCA extends the FI, providing additional health information, and allows us to explore system dimensionality and complexity. PCA is a promising tool for determining and exploring collective health features from collections of binarized biomarkers.
    Keywords:  Aging; Biological age; Dimensionality reduction; Frailty index; Logistic principal component analysis; Principal component analysis
  8. CMAJ. 2023 Jan 23. 195(3): E125-E126
  9. Leuk Res. 2023 Jan 24. pii: S0145-2126(23)00007-3. [Epub ahead of print]126 107022
      Mosaic chromosomal alterations (mCAs) are the clonal expansion of large somatically acquired structural chromosomal changes present on the autosomes and sex chromosomes. Most studies of mCAs use existing genotype array intensity data from large populations to investigate potential risk factors and disease outcomes associated with mCAs. In this review, we perform a comprehensive examination of existing evidence for mCA disease and mortality associations and provide a framework for interpreting these associations in the context of important biases specific to mCA studies. Our goal is to motivate well-designed mCA studies to assist in unlocking the potential of mCAs to improve understanding of the effects of ageing and accelerate translational applications for improving public health.
    Keywords:  Clonal hematopoiesis; Disease risk; Epidemiology; Mosaic chromosomal alterations; Risk factors
  10. Front Public Health. 2022 ;10 1037544
      A long-standing human lifespan debate is revival, and the consensus is yet to come on whether the maximum human lifespan is reaching a limit or not. This study discusses how mathematical constraints inherent in survival curves indicate a limit on maximum lifespans, implying that humans would have inevitable limits to lifespan growth.
    Keywords:  lifespan; mathematical constraints; stretched exponential model; supercentenarians; survival curve