bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2024–05–12
eleven papers selected by
Ayesh Seneviratne, Western University
  1. Rebalancing the aged immune system.
  2. SASP in peripartum cardiomyopathy and preeclampsia.
  3. Hacking the immune system could slow ageing - here's how.
  4. Aging clocks based on accumulating stochastic variation.
  5. Cellular senescence, DNA damage, and neuroinflammation in the aging brain.
  6. Determinants of mosaic chromosomal alteration fitness.
  7. Acute Kidney Injury, Systemic Inflammation and Long-term Cognitive Function: ASSESS-AKI.
  8. The role of pericyte GSK3β in renal aging and disease.
  9. New Directions in Geroscience: Integrating Social and Behavioral Drivers of Biological Aging.
  10. Acetylcholinesterase Inhibitors, AMD, and Alzheimer Disease-Reply.
  11. Frailty in Patients on Dialysis.
  1. Nat Aging. 2024 May 08.
    Rebalancing the aged immune system.
    Hannah Walters.
      
    DOI:  https://doi.org/10.1038/s43587-024-00637-9
  2. Nat Aging. 2024 May 09.
    SASP in peripartum cardiomyopathy and preeclampsia.
    Anna Kriebs.
      
    DOI:  https://doi.org/10.1038/s43587-024-00638-8
  3. Nature. 2024 May;629(8011): 276-278
    Hacking the immune system could slow ageing - here's how.
    Alison Abbott.
      
    Keywords:  Ageing; Immunology; Medical research
    DOI:  https://doi.org/10.1038/d41586-024-01274-3
  4. Nat Aging. 2024 May 09.
    Aging clocks based on accumulating stochastic variation.
    David H Meyer, Björn Schumacher.
      Aging clocks have provided one of the most important recent breakthroughs in the biology of aging, and may provide indicators for the effectiveness of interventions in the aging process and preventive treatments for age-related diseases. The reproducibility of accurate aging clocks has reinvigorated the debate on whether a programmed process underlies aging. Here we show that accumulating stochastic variation in purely simulated data is sufficient to build aging clocks, and that first-generation and second-generation aging clocks are compatible with the accumulation of stochastic variation in DNA methylation or transcriptomic data. We find that accumulating stochastic variation is sufficient to predict chronological and biological age, indicated by significant prediction differences in smoking, calorie restriction, heterochronic parabiosis and partial reprogramming. Although our simulations may not explicitly rule out a programmed aging process, our results suggest that stochastically accumulating changes in any set of data that have a ground state at age zero are sufficient for generating aging clocks.
    DOI:  https://doi.org/10.1038/s43587-024-00619-x
  5. Trends Neurosci. 2024 May 09. pii: S0166-2236(24)00061-4. [Epub ahead of print]
    Cellular senescence, DNA damage, and neuroinflammation in the aging brain.
    Wenyan Zhang, Hong-Shuo Sun, Xiaoying Wang, Aaron S Dumont, Qiang Liu.
      Aging may lead to low-level chronic inflammation that increases the susceptibility to age-related conditions, including memory impairment and progressive loss of brain volume. As brain health is essential to promoting healthspan and lifespan, it is vital to understand age-related changes in the immune system and central nervous system (CNS) that drive normal brain aging. However, the relative importance, mechanistic interrelationships, and hierarchical order of such changes and their impact on normal brain aging remain to be clarified. Here, we synthesize accumulating evidence that age-related DNA damage and cellular senescence in the immune system and CNS contribute to the escalation of neuroinflammation and cognitive decline during normal brain aging. Targeting cellular senescence and immune modulation may provide a logical rationale for developing new treatment options to restore immune homeostasis and counteract age-related brain dysfunction and diseases.
    Keywords:  brain aging; brain barriers; immunity; neurodegeneration; neuroinflammation
    DOI:  https://doi.org/10.1016/j.tins.2024.04.003
  6. Nat Commun. 2024 May 07. 15(1): 3800
    Determinants of mosaic chromosomal alteration fitness.
    Yash Pershad, Taralynn Mack, Hannah Poisner, Yasminka A Jakubek, Adrienne M Stilp, Braxton D Mitchell, Joshua P Lewis, Eric Boerwinkle, Ruth J F Loos, Nathalie Chami, Zhe Wang, Kathleen Barnes, Nathan Pankratz, Myriam Fornage, Susan Redline, Bruce M Psaty, Joshua C Bis, Ali Shojaie, Edwin K Silverman, Michael H Cho, Jeong H Yun, Dawn DeMeo, Daniel Levy, Andrew D Johnson, Rasika A Mathias, Margaret A Taub, Donna Arnett, Kari E North, Laura M Raffield, April P Carson, Margaret F Doyle, Stephen S Rich, Jerome I Rotter, Xiuqing Guo, Nancy J Cox, Dan M Roden, Nora Franceschini, Pinkal Desai, Alex P Reiner, Paul L Auer, Paul A Scheet, Siddhartha Jaiswal, Joshua S Weinstock, Alexander G Bick.
      Clonal hematopoiesis (CH) is characterized by the acquisition of a somatic mutation in a hematopoietic stem cell that results in a clonal expansion. These driver mutations can be single nucleotide variants in cancer driver genes or larger structural rearrangements called mosaic chromosomal alterations (mCAs). The factors that influence the variations in mCA fitness and ultimately result in different clonal expansion rates are not well understood. We used the Passenger-Approximated Clonal Expansion Rate (PACER) method to estimate clonal expansion rate as PACER scores for 6,381 individuals in the NHLBI TOPMed cohort with gain, loss, and copy-neutral loss of heterozygosity mCAs. Our mCA fitness estimates, derived by aggregating per-individual PACER scores, were correlated (R2 = 0.49) with an alternative approach that estimated fitness of mCAs in the UK Biobank using population-level distributions of clonal fraction. Among individuals with JAK2 V617F clonal hematopoiesis of indeterminate potential or mCAs affecting the JAK2 gene on chromosome 9, PACER score was strongly correlated with erythrocyte count. In a cross-sectional analysis, genome-wide association study of estimates of mCA expansion rate identified a TCL1A locus variant associated with mCA clonal expansion rate, with suggestive variants in NRIP1 and TERT.
    DOI:  https://doi.org/10.1038/s41467-024-48190-8
  7. Clin J Am Soc Nephrol. 2024 May 10.
    Acute Kidney Injury, Systemic Inflammation and Long-term Cognitive Function: ASSESS-AKI.
    Pavan K Bhatraju, Leila R Zelnick, Ian B Stanaway, T Alp Ikizler, Steven Menez, Vernon M Chinchilli, Steve G Coca, James S Kaufman, Paul L Kimmel, Chirag R Parikh, Alan S Go, Edward D Siew, Mark M Wurfel, Jonathan Himmelfarb.
       BACKGROUND: Cognitive dysfunction is a well-known complication of chronic kidney disease, but it is less known whether cognitive decline occurs in survivors after acute kidney injury (AKI). We hypothesized that an episode of AKI is associated with poorer cognitive function, mediated, at least in part, by persistent systemic inflammation.
    METHODS: ASSESS-AKI enrolled patients surviving three months after hospitalization with and without AKI matched based on demographics, comorbidities, and baseline kidney function. A subset underwent cognitive testing using the modified mini-mental status examination (3MS) at 3, 12, and 36 months. We examined the association of AKI with 3MS scores using mixed linear models and assessed the proportion of risk mediated by systemic inflammatory biomarkers.
    RESULTS: Among 1538 participants in ASSESS-AKI, 1420 (92%) completed the 3MS assessment at 3 months and had a corresponding matched participant. Participants with AKI had lower 3MS scores at three years (difference -1.1 (95% CI: -2.0, -0.3) P=0.009) compared to participants without AKI. A higher proportion of AKI participants had a clinically meaningful (≥ 5 point) reduction in 3MS scores at three years compared to participants without AKI (14% vs. 10%, P=0.04). In mediation analyses, plasma soluble tumor necrosis factor receptor-1 (sTNFR-1) at three months after AKI mediated 35% (P=0.02) of the AKI related risk for 3MS scores at three years.
    CONCLUSIONS: AKI was associated with lower 3MS scores and sTNFR-1 concentrations appeared to mediate a significant proportion of the risk of long-term cognitive impairment. Further work is needed to determine if AKI is causal or a marker for cognitive impairment.
    DOI:  https://doi.org/10.2215/CJN.0000000000000473
  8. J Formos Med Assoc. 2024 May 09. pii: S0929-6646(24)00240-7. [Epub ahead of print]
    The role of pericyte GSK3β in renal aging and disease.
    Yu-En Chen, Szu-Yu Pan, Yu-Hsiang Chou.
      
    DOI:  https://doi.org/10.1016/j.jfma.2024.05.004
  9. Psychosom Med. 2024 May 09.
    New Directions in Geroscience: Integrating Social and Behavioral Drivers of Biological Aging.
    Lisbeth Nielsen, Anna L Marsland, Elissa J Hamlat, Elissa S Epel.
       ABSTRACT: The "geroscience hypothesis" posits that slowing the physiological processes of aging would lead to delayed disease onset and longer healthspan and lifespan. This shift from a focus on solely treating existing disease to slowing the aging process is a shift toward prevention, including a focus on risk factors found in the social environment. While geroscience traditionally has focused on the molecular and cellular drivers of biological aging, more fundamental causes of aging may be found in the social exposome - the complex array of human social environmental exposures that shape health and disease. The social exposome may interact with physiological processes to accelerate aging biology. In this commentary, we review the potential of these insights to shape the emerging field of translational geroscience. The articles in this special issue highlight how social stress and social determinants of health are associated with biomarkers of aging such as inflammation, epigenetic clocks, and telomeres, and spotlight promising interventions to mitigate stress-related inflammation. For geroscience to incorporate the social exposome into its translational agenda, studies are needed that elucidate and quantify the effects of social exposures on aging and that consider social exposures as intervention targets. The life course perspective allows us to measure both exposures and aging biology over time including sensitive periods of development and major social transitions. In addition, given rapid changes in the measurement of aging biology, which include machine learning techniques, multisystem phenotypes of aging are being developed to better reflect whole body aging, replacing reliance on single system biomarkers. In this expanded and more integrated field of translational geroscience, strategies targeting factors in the social exposome hold promise for achieving aging health equity and extending healthy longevity.
    DOI:  https://doi.org/10.1097/PSY.0000000000001320
  10. JAMA Ophthalmol. 2024 May 09.
    Acetylcholinesterase Inhibitors, AMD, and Alzheimer Disease-Reply.
    Joseph Magagnoli, S Scott Sutton, Jayakrishna Ambati.
      
    DOI:  https://doi.org/10.1001/jamaophthalmol.2024.1204
  11. Kidney Int. 2024 May 03. pii: S0085-2538(24)00315-6. [Epub ahead of print]
    Frailty in Patients on Dialysis.
    Gordon Chun-Kau Chan, Kamyar Kalantar-Zadeh, Jack Kit-Chung Ng, Na Tian, Aine Burns, Kai-Ming Chow, Cheuk-Chun Szeto, Philip Kam-Tao Li.
      Frailty is a condition that is frequently observed among patients performing dialysis. It is characterised by a decline in both physiological and cognitive state, leading to a combination of symptoms such as weight loss, exhaustion, low physical activity, weakness, and slow walking speed. Frail patients not only experience a poor quality of life, but they are also at a higher risk of hospitalization, infection, cardiovascular events, dialysis-associated complications, and death. Frailty occurs as a result of a combination and interaction of various medical issues in patients who are on dialysis. Unfortunately, there is no cure for frailty. To address frailty, a multifaceted approach is necessary, involving coordinated efforts from nephrologists, geriatricians, nurses, allied health practitioners, and family members. Strategies such as optimizing nutrition and CKD-related complications, reducing polypharmacy by deprescription, personalized dialysis prescription and considering home-based or assisted dialysis may help slow the decline of physical function over time in subjects with frailty. This review discusses the underlying causes of frailty in patients on dialysis and examines the methods and difficulties involved in managing frailty among this group.
    DOI:  https://doi.org/10.1016/j.kint.2024.02.026
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