bims-agimec Biomed News
on Aging mechanisms
Issue of 2024–08–25
seven papers selected by
Metin Sökmen, Ankara Üniversitesi
  1. Aging and physiological barriers: mechanisms of barrier integrity changes and implications for age-related diseases.
  2. Research progress on interferon and cellular senescence.
  3. Benefit delayed immunosenescence by regulating CD4+T cells: A promising therapeutic target for aging-related diseases.
  4. Targeting multiple hallmarks of mammalian aging with combinations of interventions.
  5. MicroRNAs and their Modulatory Effect on the Hallmarks of Osteosarcopenia.
  6. Targeting mitochondrial quality control: new therapeutic strategies for major diseases.
  7. Hormonal orchestra: mastering mitochondria's role in health and disease.
  1. Mol Biol Rep. 2024 Aug 19. 51(1): 917
    Aging and physiological barriers: mechanisms of barrier integrity changes and implications for age-related diseases.
    Ilya Solovev, Alena Sergeeva, Anastasya Geraskina, Mikhail Shaposhnikov, Maria Vedunova, Olga Borysova, Alexey Moskalev.
      The phenomenon of compartmentalization is one of the key traits of life. Biological membranes and histohematic barriers protect the internal environment of the cell and organism from endogenous and exogenous impacts. It is known that the integrity of these barriers decreases with age due to the loss of homeostasis, including age-related gene expression profile changes and the abnormal folding/assembly, crosslinking, and cleavage of barrier-forming macromolecules in addition to morphological changes in cells and tissues. The critical molecular and cellular mechanisms involved in physiological barrier integrity maintenance and aging-associated changes in their functioning are reviewed on different levels: molecular, organelle, cellular, tissue (histohematic, epithelial, and endothelial barriers), and organ one (skin). Biogerontology, which studies physiological barriers in the aspect of age, is still in its infancy; data are being accumulated, but there is no talk of the synthesis of complex theories yet. This paper mainly presents the mechanisms that will become targets of anti-aging therapy only in the future, possibly: pharmacological, cellular, and gene therapies, including potential geroprotectors, hormetins, senomorphic drugs, and senolytics.
    Keywords:  Aging; Barrier integrity maintenance; Histohematic barriers; Physiological barriers; Target molecules
    DOI:  https://doi.org/10.1007/s11033-024-09833-7
  2. FASEB J. 2024 Aug 31. 38(16): e70000
    Research progress on interferon and cellular senescence.
    Da Wang, Kaixian Chen, Zheng Wang, Huali Wu, Yiming Li.
      Since the 12 major signs of aging were revealed in 2023, people's interpretation of aging will go further, which is of great significance for understanding the occurrence, development, and intervention in the aging process. As one of the 12 major signs of aging, cellular senescence refers to the process in which the proliferation and differentiation ability of cells decrease under stress stimulation or over time, often manifested as changes in cell morphology, cell cycle arrest, and decreased metabolic function. Interferon (IFN), as a secreted ligand for specific cell surface receptors, can trigger the transcription of interferon-stimulated genes (ISGs) and play an important role in cellular senescence. In addition, IFN serves as an important component of SASP, and the activation of the IFN signaling pathway has been shown to contribute to cell apoptosis and senescence. It is expected to delay cellular senescence by linking IFN with cellular senescence and studying the effects of IFN on cellular senescence and its mechanism. This article provides a review of the research on the relationship between IFN and cellular senescence by consulting relevant literature.
    Keywords:  body aging; cellular senescence; interaction; interferon; mechanism of action
    DOI:  https://doi.org/10.1096/fj.202400808RR
  3. Aging Cell. 2024 Aug 18. e14317
    Benefit delayed immunosenescence by regulating CD4+T cells: A promising therapeutic target for aging-related diseases.
    Tingting Xia, Ying Zhou, Jiayao An, Zhi Cui, Xinqin Zhong, Tianyi Cui, Bin Lv, Xin Zhao, Xiumei Gao.
      CD4+T cells play a notable role in immune protection at different stages of life. During aging, the interaction between the body's internal and external environment and CD4+T cells results in a series of changes in the CD4+T cells pool making it involved in immunosenescence. Many studies have extensively examined the subsets and functionality of CD4+T cells within the immune system, highlighted their pivotal role in disease pathogenesis, progression, and therapeutic interventions. However, the underlying mechanism of CD4+T cells senescence and its intricate association with diseases remains to be elucidated and comprehensively understood. By summarizing the immunosenescent progress and network of CD4+T cell subsets, we reveal the crucial role of CD4+T cells in the occurrence and development of age-related diseases. Furthermore, we provide new insights and theoretical foundations for diseases targeting CD4+T cell subsets aging as a treatment focus, offering novel approaches for therapy, especially in infections, cancers, autoimmune diseases, and other diseases in the elderly.
    Keywords:  Naïve CD4+T cells; aging‐related diseases; effector CD4+T cells; immunosenescence; memory CD4+T cells
    DOI:  https://doi.org/10.1111/acel.14317
  4. Aging (Albany NY). 2024 Aug 18. 16
    Targeting multiple hallmarks of mammalian aging with combinations of interventions.
    Alexander Y Panchin, Anna Ogmen, Artem S Blagodatski, Anastasia Egorova, Mikhail Batin, Timofey Glinin.
      Aging is currently viewed as a result of multiple biological processes that manifest themselves independently, reinforce each other and in their totality lead to the aged phenotype. Genetic and pharmaceutical approaches targeting specific underlying causes of aging have been used to extend the lifespan and healthspan of model organisms ranging from yeast to mammals. However, most interventions display only a modest benefit. This outcome is to be expected if we consider that even if one aging process is successfully treated, other aging pathways may remain intact. Hence solving the problem of aging may require targeting not one but many of its underlying causes at once. Here we review the challenges and successes of combination therapies aimed at increasing the lifespan of mammals and propose novel directions for their development. We conclude that both additive and synergistic effects on mammalian lifespan can be achieved by combining interventions that target the same or different hallmarks of aging. However, the number of studies in which multiple hallmarks were targeted simultaneously is surprisingly limited. We argue that this approach is as promising as it is understudied.
    Keywords:  aging; combination therapy; hallmarks; lifespan and healthspan; mouse; synergistic effect
    DOI:  https://doi.org/10.18632/aging.206078
  5. Curr Osteoporos Rep. 2024 Aug 20.
    MicroRNAs and their Modulatory Effect on the Hallmarks of Osteosarcopenia.
    William J Silva, André Cruz, Gustavo Duque.
       PURPOSE OF THE REVIEW: Osteosarcopenia is a geriatric syndrome associated with disability and mortality. This review summarizes the key microRNAs that regulate the hallmarks of sarcopenia and osteoporosis. Our objective was to identify components similarly regulated in the pathology and have therapeutic potential by influencing crucial cellular processes in both bone and skeletal muscle.
    RECENT FINDINGS: The simultaneous decline in bone and muscle in osteosarcopenia involves a complex crosstalk between these tissues. Recent studies have uncovered several key mechanisms underlying this condition, including the disruption of cellular signaling pathways that regulate bone remodeling and muscle function and regeneration. Accordingly, emerging evidence reveals that dysregulation of microRNAs plays a significant role in the development of each of these hallmarks of osteosarcopenia. Although the recent recognition of osteosarcopenia as a single diagnosis of bone and muscle deterioration has provided new insights into the mechanisms of these underlying age-related diseases, several knowledge gaps have emerged, and a deeper understanding of the role of common microRNAs is still required. In this study, we summarize current evidence on the roles of microRNAs in the pathogenesis of osteosarcopenia and identify potential microRNA targets for treating this condition. Among these, microRNAs-29b and -128 are upregulated in the disease and exert adverse effects by inhibiting IGF-1 and SIRT1, making them potential targets for developing inhibitors of their activity. MicroRNA-21 is closely associated with the occurrence of muscle and bone loss. Conversely, microRNA-199b is downregulated in the disease, and its reduced activity may be related to increased myostatin and GSK3β activity, presenting it as a target for developing analogues that restore its function. Finally, microRNA-672 stands out for its ability to protect skeletal muscle and bone when expressed in the disease, highlighting its potential as a possible therapy for osteosarcopenia.
    Keywords:  Bone-muscle crosstalk; MicroRNAs; Non-coding RNA; Osteoporosis; Osteosarcopenia; Sarcopenia
    DOI:  https://doi.org/10.1007/s11914-024-00880-4
  6. Mil Med Res. 2024 Aug 21. 11(1): 59
    Targeting mitochondrial quality control: new therapeutic strategies for major diseases.
    Wei-Long Hong, He Huang, Xue Zeng, Chen-Yang Duan.
      Mitochondria play a crucial role in maintaining the normal physiological state of cells. Hence, ensuring mitochondrial quality control is imperative for the prevention and treatment of numerous diseases. Previous reviews on this topic have however been inconsistencies and lack of systematic organization. Therefore, this review aims to provide a comprehensive and systematic overview of mitochondrial quality control and explore the possibility of targeting the same for the treatment of major diseases. This review systematically summarizes three fundamental characteristics of mitochondrial quality control, including mitochondrial morphology and dynamics, function and metabolism, and protein expression and regulation. It also extensively examines how imbalances in mitochondrial quality are linked to major diseases, such as ischemia-hypoxia, inflammatory disorders, viral infections, metabolic dysregulations, degenerative conditions, and tumors. Additionally, the review explores innovative approaches to target mitochondrial quality control, including using small molecule drugs that regulate critical steps in maintaining mitochondrial quality, nanomolecular materials designed for precise targeting of mitochondria, and novel cellular therapies, such as vesicle therapy and mitochondrial transplantation. This review offers a novel perspective on comprehending the shared mechanisms underlying the occurrence and progression of major diseases and provides theoretical support and practical guidance for the clinical implementation of innovative therapeutic strategies that target mitochondrial quality control for treating major diseases.
    Keywords:  Major diseases; Mitochondrial quality control; Mitochondrial targeted therapy
    DOI:  https://doi.org/10.1186/s40779-024-00556-1
  7. Endocrine. 2024 Aug 22.
    Hormonal orchestra: mastering mitochondria's role in health and disease.
    Ebtesam Al-Suhaimi, Rahaf AlQuwaie, Reem AlSaqabi, Dwi Winarni, Firli Rahmah Primula Dewi, Abdullah A AlRubaish, Adeeb Shehzad, Abdelhamid Elaissari.
      Mitochondria is a subcellular organelle involved in the pathogenesis of cellular stress, immune responses, differentiation, metabolic disorders, aging, and death by regulating process of fission, fusion, mitophagy, and transport. However, an increased interest in mitochondria as powerhouse for ATP production, the mechanisms of mitochondria-mediated cellular dysfunction in response to hormonal interaction remains unknown. Mitochondrial matrix contains chaperones and proteases that regulate intrinsic apoptosis pathway through pro-apoptotic Bcl-2 family's proteins Bax/Bak, and Cyt C release, and induces caspase-dependent and independent cells death. Energy and growth regulators such as thyroid hormones have profound effect on mitochondrial inner membrane protein and lipid compositions, ATP production by regulating oxidative phosphorylation system. Mitochondria contain cholesterol side-chain cleavage enzyme, P450scc, ferredoxin, and ferredoxin reductase providing an essential site for steroid hormones biosynthesis. In line with this, neurohormones such as oxytocin, vasopressin, and melatonin are correlated with mitochondrial integrity, displaying therapeutic implications for inflammatory and immune responses. Melatonin's also displayed protective role against oxidative stress and mitochondrial synthesis of ROS, suggesting a defense mechanism against aging-related diseases. An imbalance in mitochondrial bioenergetics can cause neurodegenerative disorders, cardiovascular diseases, and cancers. Hormone-induced PGC-1α stimulates mitochondrial biogenesis via activation of NRF1 and NRF2, which in turn triggers mtTFA in brown adipose and cardiac myocytes. Mitochondria can be transferred through cells merging, exosome-mediated transfer, and tunneling through nanotubes. By delineating the underlying molecular mechanism of hormonal mitochondrial interaction, this study reviews the dynamics mechanisms of mitochondria and its effects on cellular level, health, diseases, and therapeutic strategies targeting mitochondrial diseases.
    Keywords:  Bioenergetics; Brain Disease; Hormones; Mitochondria; Pathophysiology
    DOI:  https://doi.org/10.1007/s12020-024-03967-1
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