bims-minfam Biomed News
on Inflammation and metabolism in ageing and cancer
Issue of 2023–02–05
twelve papers selected by
Ayesh Seneviratne, Western University
  1. Protein translation paradox: Implications in translational regulation of aging.
  2. Single-cell aging clocks.
  3. Editorial: Frailty: Risks and management.
  4. Caloric restriction induced epigenetic effects on aging.
  5. Is Human Aging a Form of Phenoptosis?
  6. Inflammaging as a target for healthy ageing.
  7. Mitochondrial DNA and inflammatory proteins are higher in extracellular vesicles from frail individuals.
  8. Editorial: Metabolic miscommunication among organs: The missing links.
  9. Age-dependent nuclear lipid droplet deposition is a cellular hallmark of aging in Caenorhabditis elegans.
  10. Activity-friendly environments for active aging: The physical, social, and technology environments.
  11. A study on the prevalence and related factors of frailty and pre-frailty in the older population with hypertension in China: A national cross-sectional study.
  12. Impaired iron recycling from erythrocytes is an early hallmark of aging.
  1. Front Cell Dev Biol. 2023 ;11 1129281
    Protein translation paradox: Implications in translational regulation of aging.
    Harper S Kim, Andrew M Pickering.
      Protein translation is an essential cellular process playing key roles in growth and development. Protein translation declines over the course of age in multiple animal species, including nematodes, fruit flies, mice, rats, and even humans. In all these species, protein translation transiently peaks in early adulthood with a subsequent drop over the course of age. Conversely, lifelong reductions in protein translation have been found to extend lifespan and healthspan in multiple animal models. These findings raise the protein synthesis paradox: age-related declines in protein synthesis should be detrimental, but life-long reductions in protein translation paradoxically slow down aging and prolong lifespan. This article discusses the nature of this paradox and complies an extensive body of work demonstrating protein translation as a modulator of lifespan and healthspan.
    Keywords:  ageing; aging; eIF; hallmarks of aging; lifespan; protein translation; sk6; theories of aging
    DOI:  https://doi.org/10.3389/fcell.2023.1129281
  2. Lab Anim (NY). 2023 Feb;52(2): 33
    Single-cell aging clocks.
    Charlotte Harrison.
      
    DOI:  https://doi.org/10.1038/s41684-023-01118-z
  3. Front Med (Lausanne). 2023 ;10 1100557
    Editorial: Frailty: Risks and management.
    Leonardo Bencivenga, Karolina Piotrowicz.
      
    Keywords:  aging; frailty; geriatric medicine; geriatric syndrome; older adults
    DOI:  https://doi.org/10.3389/fmed.2023.1100557
  4. Front Cell Dev Biol. 2022 ;10 1079920
    Caloric restriction induced epigenetic effects on aging.
    Jingfang Zhai, William H Kongsberg, Yinbo Pan, Canhua Hao, Xiaojing Wang, Jie Sun.
      Aging is the subject of many studies, facilitating the discovery of many interventions. Epigenetic influences numerous life processes by regulating gene expression and also plays a crucial role in aging regulation. Increasing data suggests that dietary changes can alter epigenetic marks associated with aging. Caloric restriction (CR)is considered an intervention to regulate aging and prolong life span. At present, CR has made some progress by regulating signaling pathways associated with aging as well as the mechanism of action of intercellular signaling molecules against aging. In this review, we will focus on autophagy and epigenetic modifications to elaborate the molecular mechanisms by which CR delays aging by triggering autophagy, epigenetic modifications, and the interaction between the two in caloric restriction. In order to provide new ideas for the study of the mechanism of aging and delaying aging.
    Keywords:  aging; autophagy; caloric restriction; drugs; epigenetic
    DOI:  https://doi.org/10.3389/fcell.2022.1079920
  5. Biochemistry (Mosc). 2022 Dec;87(12): 1446-1464
    Is Human Aging a Form of Phenoptosis?
    Giacinto Libertini, Graziamaria Corbi, Olga Shubernetskaya, Nicola Ferrara.
      A much debated question is whether aging is the cumulative consequence of degenerative factors insufficiently opposed by natural selection, or, on the contrary, an ordered process, genetically determined and regulated, modeled by natural selection, and for which the definition of phenoptotic phenomenon would be entirely appropriate. In this review, theoretical arguments and empirical data about the two hypotheses are exposed, with more evidence in support of the thesis of aging as a form of phenoptosis. However, as the thesis of aging as an adaptive and programmed phenomenon necessarily requires the existence of specific mechanisms that determine to age, such as the subtelomere-telomere theory proposed for this purpose, the evidence supporting the mechanisms described by this theory is reported. In particular, it is highlighted that the recent interpretation of the role of TERRA sequences in the context of subtelomere-telomere theory is a fundamental point in supporting the hypothesized mechanisms. Furthermore, some characteristics of the mechanisms proposed by the theory, such as epigenetic modifications in aging, gradual cell senescence, cell senescence, limits in cell duplications, and fixed size of the telomeric heterochromatin hood, are exposed in their compatibility with both the thesis of aging as phenoptotic phenomenon and the opposite thesis. In short, aging as a form of phenoptosis appears a scientifically sound hypothesis while the opposite thesis should clarify the meaning of various phenomena that appear to invalidate it.
    Keywords:  aging; cell senescence; epigenetic changes; gradual cell senescence; phenoptosis; subtelomere; subtelomere–telomere theory; telomere
    DOI:  https://doi.org/10.1134/S0006297922120033
  6. Age Ageing. 2023 Feb 01. pii: afac328. [Epub ahead of print]52(2):
    Inflammaging as a target for healthy ageing.
    Ben Dugan, Jessica Conway, Niharika A Duggal.
      Life expectancy has been on the rise for the past few decades, but healthy life expectancy has not kept pace, leading to a global burden of age-associated disorders. Advancing age is accompanied by a chronic increase in basal systemic inflammation, termed inflammaging, contributing towards an increased risk of developing chronic diseases in old age. This article reviews the recent literature to formulate hypotheses regarding how age-associated inflammaging plays a crucial role in driving chronic diseases and ill health in older adults. Here, we discuss how non-pharmacological intervention strategies (diet, nutraceutical supplements, phytochemicals, physical activity, microbiome-based therapies) targeting inflammaging restore health in older adults. We also consider alternative existing pharmacological interventions (Caloric restriction mimetics, p38 mitogen-activated protein kinase inhibitors) and explore novel targets (senolytics) aimed at combating inflammaging and optimising the ageing process to increase healthy lifespan.
    Keywords:  ageing; inflammaging; inflammation; interventions; older people; review
    DOI:  https://doi.org/10.1093/ageing/afac328
  7. Immun Ageing. 2023 Jan 30. 20(1): 6
    Mitochondrial DNA and inflammatory proteins are higher in extracellular vesicles from frail individuals.
    Anjali M Byappanahalli, Nicole Noren Hooten, Mya Vannoy, Nicolle A Mode, Ngozi Ezike, Alan B Zonderman, Michele K Evans.
       BACKGROUND: Frailty, a clinical syndrome commencing at midlife, is a risk for morbidity and mortality. Little is known about the factors that contribute to the chronic inflammatory state associated with frailty. Extracellular vesicles (EVs) are small, membrane-bound vesicles that are released into the circulation and are mediators of intercellular communication. We examined whether mitochondrial DNA (mtDNA) and inflammatory proteins in EVs may act as damage-associated molecular pattern (DAMP) molecules in frailty.
    RESULTS: To address whether EVs and their associated mtDNA and inflammatory protein cargo are altered with frailty, EVs were isolated from non-frail (n = 90) and frail (n = 87) middle-aged (45-55 years) participants from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. EV concentration was highest in frail White participants. EV mtDNA levels were significantly higher in frail individuals compared to non-frail individuals. The presence of six inflammatory proteins in EVs (FGF-21, HGF, IL-12B, PD-L1, PRDX3, and STAMBP) were significantly associated with frailty. EV inflammatory proteins were significantly altered by frailty status, race, sex, and poverty status. Notably, frail White participants had higher levels of EV-associated CD5, CD8A, CD244, CXCL1, CXCL6, CXCL11, LAP-TGF-beta-1 and MCP-4 compared to frail and non-frail African American participants. Frail White participants living below poverty had higher levels of EV-associated uPA. EV-associated CCL28 levels were highest in non-frail women and CXCL1 were highest in non-frail men. Men living below poverty had higher levels of CD5, CD8A, CXCL1, LAP-TGF-beta-1, and uPA. CXCL6 levels were significantly higher in individuals living above poverty. There was a significant correlation between EV mtDNA levels and the presence of inflammatory proteins.
    CONCLUSIONS: These data suggest that mtDNA within EVs may act as a DAMP molecule in frailty. Its association with chemokines and other inflammatory EV cargo proteins, may contribute to the frailty phenotype. In addition, the social determinant of health, poverty, influences the inflammatory cargo of EVs in midlife.
    Keywords:  Aging; DAMP; EV; Exosome; Frail; Health disparities; Mitochondria, mtDNA, inflammation; Proteins; Social determinants of health
    DOI:  https://doi.org/10.1186/s12979-023-00330-2
  8. Front Endocrinol (Lausanne). 2023 ;14 1136283
    Editorial: Metabolic miscommunication among organs: The missing links.
    Maria João Meneses, Maria Paula Macedo.
      
    Keywords:   diabetes; NAFLD; crosstalk; exercise; inflammation; metabolism
    DOI:  https://doi.org/10.3389/fendo.2023.1136283
  9. Aging Cell. 2023 Jan 31. e13788
    Age-dependent nuclear lipid droplet deposition is a cellular hallmark of aging in Caenorhabditis elegans.
    Konstantinos Palikaras, Meropi Mari, Christina Ploumi, Andrea Princz, George Filippidis, Nektarios Tavernarakis.
      Aging is the major risk factor for several life-threatening pathologies and impairs the function of multiple cellular compartments and organelles. Age-dependent deterioration of nuclear morphology is a common feature in evolutionarily divergent organisms. Lipid droplets have been shown to localize in most nuclear compartments, where they impinge on genome architecture and integrity. However, the significance of progressive nuclear lipid accumulation and its impact on organismal homeostasis remain obscure. Here, we implement non-linear imaging modalities to monitor and quantify age-dependent nuclear lipid deposition in Caenorhabditis elegans. We find that lipid droplets increasingly accumulate in the nuclear envelope, during aging. Longevity-promoting interventions, such as low insulin signaling and caloric restriction, abolish the rate of nuclear lipid accrual and decrease the size of lipid droplets. Suppression of lipotoxic lipid accumulation in hypodermal and intestinal nuclei is dependent on the transcription factor HLH-30/TFEB and the triglyceride lipase ATGL-1. HLH-30 regulates the expression of ATGL-1 to reduce nuclear lipid droplet abundance in response to lifespan-extending conditions. Notably, ATGL-1 localizes to the nuclear envelope and moderates lipid content in long-lived mutant nematodes during aging. Our findings indicate that the reduced ATGL-1 activity leads to excessive nuclear lipid accumulation, perturbing nuclear homeostasis and undermining organismal physiology, during aging.
    Keywords:  ATGL-1; HLH-30/TFEB; aging; lipid droplet; non-linear optical phenomena; nucleus
    DOI:  https://doi.org/10.1111/acel.13788
  10. Front Public Health. 2022 ;10 1080148
    Activity-friendly environments for active aging: The physical, social, and technology environments.
    Erja Portegijs, Chanam Lee, Xuemei Zhu.
      
    Keywords:  active aging; activity-friendly community; physical environment; social environment; technology environment
    DOI:  https://doi.org/10.3389/fpubh.2022.1080148
  11. Front Cardiovasc Med. 2022 ;9 1057361
    A study on the prevalence and related factors of frailty and pre-frailty in the older population with hypertension in China: A national cross-sectional study.
    Xue-Zhai Zeng, Na Jia, Ling-Bing Meng, Jing Shi, Ying-Ying Li, Jia-Bin Hu, Xing Hu, Hui Li, Hong-Xuan Xu, Jian-Yi Li, Xin Qi, Hua Wang, Qiu-Xia Zhang, Juan Li, De-Ping Liu.
       Objective: To explore the prevalence and factors associated with frailty and pre-frailty in elderly Chinese patients with hypertension.
    Background: In China, there have been few national studies into the prevalence and factors associated with frailty and pre-frailty in elderly patients with hypertension.
    Methods: Through the 4th Sample Survey of Aged Population in Urban and Rural China (SSAPUR) in 2015, the situation of hypertension subjects aged 60 years or older in 31 provinces, autonomous regions, and municipalities in mainland China was obtained. And the frailty index was constructed based on 33 potential defects, elderly hypertensive patients are classified as robust, frailty, and pre-frailty.
    Results: A total of 76,801 elderly patients with hypertension were enrolled in the study. The age-sex standardized prevalence of frailty and pre-frailty in hypertensive elderly in China was 16.1% (95%CI 15.8-16.3%), 58.1% (95%CI 57.7-58.4%). There were significant geographical differences in the prevalence of frailty and pre-frailty in elderly hypertensive patients. Multinomial logistic regression analysis showed that poor economic status, activities of daily living disability, and comorbid chronic diseases were related to frailty and pre-frailty.
    Conclusion: Frailty and pre-frailty are very common in elderly Chinese patients with hypertension and have similar risk factors. Prevention strategies should be developed to stop or delay the onset of frailty by targeting established risk factors in the pre-frailty population of elderly hypertension. It is also crucial to optimize the management of frailty in elderly Chinese patients with hypertension.
    Keywords:  frailty; hypertension; older adults; pre-frailty; prevalence; related factors
    DOI:  https://doi.org/10.3389/fcvm.2022.1057361
  12. Elife. 2023 Jan 31. pii: e79196. [Epub ahead of print]12
    Impaired iron recycling from erythrocytes is an early hallmark of aging.
    Patryk Slusarczyk, Pratik Kumar Mandal, Gabriela Zurawska, Marta Niklewicz, Komal Chouhan, Raghunandan Mahadeva, Aneta Jończy, Matylda Macias, Aleksandra Szybinska, Magdalena Cybulska-Lubak, Olga Krawczyk, Sylwia Herman, Michal Mikula, Remigiusz Serwa, Malgorzata Lenartowicz, Wojciech Pokrzywa, Katarzyna Mleczko-Sanecka.
      Aging affects iron homeostasis, as evidenced by tissue iron loading and anemia in the elderly. Iron needs in mammals are met primarily by iron recycling from senescent red blood cells (RBCs), a task chiefly accomplished by splenic red pulp macrophages (RPMs) via erythrophagocytosis. Given that RPMs continuously process iron, their cellular functions might be susceptible to age-dependent decline, a possibility that has been unexplored to date. Here, we found that 10-11-month-old female mice exhibit iron loading in RPMs, largely attributable to a drop in iron exporter ferroportin, which diminishes their erythrophagocytosis capacity and lysosomal activity. Furthermore, we identified a loss of RPMs during aging, underlain by the combination of proteotoxic stress and iron-dependent cell death resembling ferroptosis. These impairments lead to the retention of senescent hemolytic RBCs in the spleen, and the formation of undegradable iron- and heme-rich extracellular protein aggregates, likely derived from ferroptotic RPMs. We further found that feeding mice an iron-reduced diet alleviates iron accumulation in RPMs, enhances their ability to clear erythrocytes, and reduces damage. Consequently, this diet ameliorates hemolysis of splenic RBCs and reduces the burden of protein aggregates, mildly increasing serum iron availability in aging mice. Taken together, we identified RPM collapse as an early hallmark of aging and demonstrated that dietary iron reduction improves iron turnover efficacy.
    Keywords:  cell biology; mouse
    DOI:  https://doi.org/10.7554/eLife.79196
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