bims-agimec Biomed News
on Aging mechanisms
Issue of 2024–11–24
seven papers selected by
Metin Sökmen, Ankara Üniversitesi
  1. Sarcopenia and the biological determinants of aging: A narrative review from a geroscience perspective.
  2. Membraneless organelles in health and disease: exploring the molecular basis, physiological roles and pathological implications.
  3. Telomeres: an organized string linking plants and mammals.
  4. Regulating translation in aging: from global to gene-specific mechanisms.
  5. Emerging insights in senescence: pathways from preclinical models to therapeutic innovations.
  6. Mechanisms of Muscle Cells Alterations and Regeneration Decline During Aging.
  7. The Causal Relationship between Genetically Predicted Biological Aging, Alzheimer's Disease and Cognitive Function: A Mendelian Randomisation Study.
  1. Ageing Res Rev. 2024 Nov 19. pii: S1568-1637(24)00405-7. [Epub ahead of print] 102587
    Sarcopenia and the biological determinants of aging: A narrative review from a geroscience perspective.
    Mariá Nunes-Pinto, Renato Gorga Bandeira de Mello, Milena Nunes Pinto, Cédric Moro, Bruno Vellas, Laurent O Martinez, Yves Rolland, Philipe de Souto Barreto.
       BACKGROUND: The physiopathology of sarcopenia shares common biological cascades with the aging process, as does any other age-related condition. However, our understanding of the interconnected pathways between diagnosed sarcopenia and aging remains limited, lacking sufficient scientific evidence.
    METHODS: This narrative review aims to gather and describe the current evidence on the relationship between biological aging determinants, commonly referred to as the hallmarks of aging, and diagnosed sarcopenia in humans.
    RESULTS: Among the twelve hallmarks of aging studied, there appears to be a substantial association between sarcopenia and mitochondrial dysfunction, epigenetic alterations, deregulated nutrient sensing, and altered intercellular communication. Although limited, preliminary evidence suggests a promising association between sarcopenia and genomic instability or stem cell exhaustion.
    DISCUSSION: Overall, an imbalance in energy regulation, characterized by impaired mitochondrial energy production and alterations in circulatory markers, is commonly associated with sarcopenia and may reflect the interplay between aging physiology and sarcopenia biology.
    Keywords:  Sarcopenia; age-related diseases; geroscience; hallmarks of aging
    DOI:  https://doi.org/10.1016/j.arr.2024.102587
  2. Signal Transduct Target Ther. 2024 Nov 18. 9(1): 305
    Membraneless organelles in health and disease: exploring the molecular basis, physiological roles and pathological implications.
    Yangxin Li, Yuzhe Liu, Xi-Yong Yu, Yan Xu, Xiangbin Pan, Yi Sun, Yanli Wang, Yao-Hua Song, Zhenya Shen.
      Once considered unconventional cellular structures, membraneless organelles (MLOs), cellular substructures involved in biological processes or pathways under physiological conditions, have emerged as central players in cellular dynamics and function. MLOs can be formed through liquid-liquid phase separation (LLPS), resulting in the creation of condensates. From neurodegenerative disorders, cardiovascular diseases, aging, and metabolism to cancer, the influence of MLOs on human health and disease extends widely. This review discusses the underlying mechanisms of LLPS, the biophysical properties that drive MLO formation, and their implications for cellular function. We highlight recent advances in understanding how the physicochemical environment, molecular interactions, and post-translational modifications regulate LLPS and MLO dynamics. This review offers an overview of the discovery and current understanding of MLOs and biomolecular condensate in physiological conditions and diseases. This article aims to deliver the latest insights on MLOs and LLPS by analyzing current research, highlighting their critical role in cellular organization. The discussion also covers the role of membrane-associated condensates in cell signaling, including those involving T-cell receptors, stress granules linked to lysosomes, and biomolecular condensates within the Golgi apparatus. Additionally, the potential of targeting LLPS in clinical settings is explored, highlighting promising avenues for future research and therapeutic interventions.
    DOI:  https://doi.org/10.1038/s41392-024-02013-w
  3. Biol Direct. 2024 Nov 20. 19(1): 119
    Telomeres: an organized string linking plants and mammals.
    Edison Di Pietro, Romina Burla, Mattia La Torre, Mary-Paz González-García, Raffaele Dello Ioio, Isabella Saggio.
      Telomeres are pivotal determinants of cell stemness, organismal aging, and lifespan. Herein, we examined similarities in telomeres of Arabidopsis thaliana, mice, and humans. We report the common traits, which include their composition in multimers of TTAGGG sequences and their protection by specialized proteins. Moreover, given the link between telomeres, on the one hand, and cell proliferation and stemness on the other, we discuss the counterintuitive convergence between plants and mammals in this regard, focusing on the impact of niches on cell stemness. Finally, we suggest that tackling the study of telomere function and cell stemness by taking into consideration both plants and mammals can aid in the understanding of interconnections and contribute to research focusing on aging and organismal lifespan determinants.
    Keywords:  Aging; Epigenetics; Humans; Lifespan; Mice; Niche; Plants; Shelterin; Stem cells; Telomeres
    DOI:  https://doi.org/10.1186/s13062-024-00558-y
  4. EMBO Rep. 2024 Nov 19.
    Regulating translation in aging: from global to gene-specific mechanisms.
    Mathilde Solyga, Amitabha Majumdar, Florence Besse.
      Aging is characterized by a decline in various biological functions that is associated with changes in gene expression programs. Recent transcriptome-wide integrative studies in diverse organisms and tissues have revealed a gradual uncoupling between RNA and protein levels with aging, which highlights the importance of post-transcriptional regulatory processes. Here, we provide an overview of multi-omics analyses that show the progressive uncorrelation of transcriptomes and proteomes during the course of healthy aging. We then describe the molecular changes leading to global downregulation of protein synthesis with age and review recent work dissecting the mechanisms involved in gene-specific translational regulation in complementary model organisms. These mechanisms include the recognition of regulated mRNAs by trans-acting factors such as miRNA and RNA-binding proteins, the condensation of mRNAs into repressive cytoplasmic RNP granules, and the pausing of ribosomes at specific residues. Lastly, we mention future challenges of this emerging field, possible buffering functions as well as potential links with disease.
    Keywords:  Aging; Post-transcriptional Regulation; RNA; RNA-Binding Proteins; Tanslation
    DOI:  https://doi.org/10.1038/s44319-024-00315-2
  5. NPJ Aging. 2024 Nov 22. 10(1): 53
    Emerging insights in senescence: pathways from preclinical models to therapeutic innovations.
    Luke Mansfield, Valentina Ramponi, Kavya Gupta, Thomas Stevenson, Abraham Binoy Mathew, Agian Jeffilano Barinda, Florencia Herbstein, Samir Morsli.
      Senescence is a crucial hallmark of ageing and a significant contributor to the pathology of age-related disorders. As committee members of the young International Cell Senescence Association (yICSA), we aim to synthesise recent advancements in the identification, characterisation, and therapeutic targeting of senescence for clinical translation. We explore novel molecular techniques that have enhanced our understanding of senescent cell heterogeneity and their roles in tissue regeneration and pathology. Additionally, we delve into in vivo models of senescence, both non-mammalian and mammalian, to highlight tools available for advancing the contextual understanding of in vivo senescence. Furthermore, we discuss innovative diagnostic tools and senotherapeutic approaches, emphasising their potential for clinical application. Future directions of senescence research are explored, underscoring the need for precise, context-specific senescence classification and the integration of advanced technologies such as machine learning, long-read sequencing, and multifunctional senoprobes and senolytics. The dual role of senescence in promoting tissue homoeostasis and contributing to chronic diseases highlights the complexity of targeting these cells for improved clinical outcomes.
    DOI:  https://doi.org/10.1038/s41514-024-00181-1
  6. Ageing Res Rev. 2024 Nov 18. pii: S1568-1637(24)00407-0. [Epub ahead of print] 102589
    Mechanisms of Muscle Cells Alterations and Regeneration Decline During Aging.
    Guntarat Chinvattanachot, Daniel Rivas, Gustavo Duque.
      Skeletal muscles are essential for locomotion and body metabolism regulation. As muscles age, they lose strength, elasticity, and metabolic capability, leading to ineffective motion and metabolic derangement. Both cellular and extracellular alterations significantly influence muscle aging. Satellite cells (SCs), the primary muscle stem cells responsible for muscle regeneration, become exhausted, resulting in diminished population and functionality during aging. This decline in SC function impairs intercellular interactions as well as extracellular matrix production, further hindering muscle regeneration. Other muscle-resident cells, such as fibro-adipogenic progenitors (FAPs), pericytes, and immune cells, also deteriorate with age, reducing local growth factor activities and responsiveness to stress or injury. Systemic signaling, including hormonal changes, contributes to muscle cellular catabolism and disrupts muscle homeostasis. Collectively, these cellular and environmental components interact, disrupting muscle homeostasis and regeneration in advancing age. Understanding these complex interactions offers insights into potential regenerative strategies to mitigate age-related muscle degeneration.
    Keywords:  Fibro-adipogenic progenitors; Satellite cells; aging; geroscience; muscle regeneration; muscle side population; stem cell exhaustion
    DOI:  https://doi.org/10.1016/j.arr.2024.102589
  7. J Prev Alzheimers Dis. 2024 ;11(6): 1826-1833
    The Causal Relationship between Genetically Predicted Biological Aging, Alzheimer's Disease and Cognitive Function: A Mendelian Randomisation Study.
    Y Hao, W Tian, B Xie, X Fu, S Wang, Y Yang.
      Aging is one of the most important risk factors for Alzheimer's disease (AD). Biological aging is a better indicator of the body's functional state than age (chronological aging). Leukocyte telomere length (LTL) and epigenetic clocks constructed from DNA methylation patterns have emerged as reliable markers of biological aging. Recent studies have shown that it may be possible to slow down or even reverse biological aging, offering promising prospects for treating AD. Several observational studies have reported an association between biological aging, AD, and cognitive function, but the causality behind this association and the effects of different biological aging markers on AD risk and cognitive function remain unclear. Therefore, we explored the causal relationship between them by Mendelian randomization (MR) study. Inverse-variance weighted (IVW) method is the most dominant analytical method in MR studies, which is a weighted average of estimates from different genotype combinations, and this weighted average provides an overall estimate of the causal effect. The results of the IVW analyses showed that HannumAge acceleration and LTL shortening were able to increase the risk of late-onset AD (LOAD), but not early-onset AD (EOAD). Excellent prospective memory and fluid intelligence are potentially protective against GrimAge acceleration. GrimAge acceleration and HorvathAge acceleration increase the risk of LOAD through effects on LTL. Our findings provide important insights into the role of biological aging in the pathogenesis of AD, while also highlighting the interplay of different biological aging markers and their complexity in different AD subtypes.
    Keywords:   cognitive function; Alzheimer’s disease; Epigenetic age acceleration; leukocyte telomere length; mendelian randomization
    DOI:  https://doi.org/10.14283/jpad.2024.128
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