bims-agimec Biomed News
on Aging mechanisms
Issue of 2025–02–02
seven papers selected by
Metin Sökmen, Ankara Üniversitesi
  1. The Intersection of Epigenetics and Senolytics in Mechanisms of Aging and Therapeutic Approaches.
  2. Engineered biomaterials in stem cell-based regenerative medicine.
  3. Roots and early routes of neuroendocrinology.
  4. Recent advances in immunotherapy targeting amyloid-beta and tauopathies in Alzheimer's disease.
  5. Brain connectivity, neural networks, and resilience in aging and neurodegeneration.
  6. A framework of biomarkers for skeletal aging: a consensus statement by the Aging Biomarker Consortium.
  7. Cancer evolution: from Darwin to the Extended Evolutionary Synthesis.
  1. Biomolecules. 2024 Dec 26. pii: 18. [Epub ahead of print]15(1):
    The Intersection of Epigenetics and Senolytics in Mechanisms of Aging and Therapeutic Approaches.
    Daiana Burdusel, Thorsten R Doeppner, Roxana Surugiu, Dirk M Hermann, Denissa Greta Olaru, Aurel Popa-Wagner.
      The biological process of aging is influenced by a complex interplay of genetic, environmental, and epigenetic factors. Recent advancements in the fields of epigenetics and senolytics offer promising avenues for understanding and addressing age-related diseases. Epigenetics refers to heritable changes in gene expression without altering the DNA sequence, with mechanisms like DNA methylation, histone modification, and non-coding RNA regulation playing critical roles in aging. Senolytics, a class of drugs targeting and eliminating senescent cells, address the accumulation of dysfunctional cells that contribute to tissue degradation and chronic inflammation through the senescence-associated secretory phenotype. This scoping review examines the intersection of epigenetic mechanisms and senolytic therapies in aging, focusing on their combined potential for therapeutic interventions. Senescent cells display distinct epigenetic signatures, such as DNA hypermethylation and histone modifications, which can be targeted to enhance senolytic efficacy. Epigenetic reprogramming strategies, such as induced pluripotent stem cells, may further complement senolytics by rejuvenating aged cells. Integrating epigenetic modulation with senolytic therapy offers a dual approach to improving healthspan and mitigating age-related pathologies. This narrative review underscores the need for continued research into the molecular mechanisms underlying these interactions and suggests future directions for therapeutic development, including clinical trials, biomarker discovery, and combination therapies that synergistically target aging processes.
    Keywords:  DNA methylation; aging mechanisms; cellular senescence; epigenetic clock; epigenetics; healthspan extension; senolytics
    DOI:  https://doi.org/10.3390/biom15010018
  2. Life Med. 2023 Aug;2(4): lnad027
    Engineered biomaterials in stem cell-based regenerative medicine.
    Fei Zhu, Guangjun Nie, Changsheng Liu.
      Stem cell-based regenerative therapies, which harness the self-renewal and differentiation properties of stem cells, have been in the spotlight due to their widespread applications in treating degenerative, aging, and other, generally intractable diseases. Therapeutically effective hematopoietic stem cells, mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells have been used in numerous basic and translational studies with exciting results. However, pre-/post-transplantation issues of poor cell survival and retention, uncontrolled differentiation, and insufficient numbers of cells engrafted into host tissues are the major challenges in stem cell-based regenerative therapies. Engineered biomaterials have adjustable biochemical and biophysical properties that significantly affect cell behaviors, such as cell engraftment, survival, migration, and differentiation outcomes, thereby enhancing the engraftment of implanted stem cells and guiding tissue regeneration. Therefore, the combination of stem cell biology with bioengineered materials is a promising strategy to improve the therapeutic outcomes of stem cell-based regenerative therapy. In this review, we summarize the advances in the modulation of behaviors of stem cells via engineered biomaterials. We then present different approaches to harnessing bioengineered materials to enhance the transplantation of stem cells. Finally, we will provide future directions in regenerative therapy using stem cells.
    Keywords:  adjustable biophysical and biochemical properties; engineered biomaterials; regenerative medicine; stem cell-based regenerative therapy; stem cells
    DOI:  https://doi.org/10.1093/lifemedi/lnad027
  3. Cell Tissue Res. 2025 Jan 30.
    Roots and early routes of neuroendocrinology.
    Esteban M Rodríguez, Montserrat Guerra, Juan Luis Blázquez.
      Carl C. Speidel (1919) and Ernst Scharrer (1928) were privileged witnesses of the encounter between neurons and hormones, a biological phenomenon that had been occurring in nature during millions of years of evolution, as Berta Scharrer started to unfold since 1935 on. The story of neurosecretion is intimately associated to that of the hypothalamus, such a "marvellous region", as Wolfgang Bargmann (1975) called it. This story started more than two millennia ago. We have made an effort to trace the roots of the discoveries that gave rise to a medical discipline, neuroendocrinology. Our trip to the roots covers a period from the fourth century BC, when an extraordinary Medical School was founded in Alexandria, and extends into the late 1970s of the twentieth century, when neuroendocrine research had started to grow exponentially. An effort has been made to track back the origin of each piece of knowledge that was constructing, brick upon brick, the building of this new medical science, hoping that it would help neuroendocrinologists of the new era to find their own roots, to meet their ancestors. Tracking the roots of a particular phenomenon provides the opportunity to have an overview of the whole phenomenon, allowing comprehension rather than merely knowledge. An important purpose pursued throughout this article was to pay a tribute to all those who, in the early days, contributed to the brain-endocrine encounter. We have tried our best to bring back the achievements of most of them.
    Keywords:  Cerebrospinal fluid; Hypophysis; Hypothalamus; Neuroendocrine integration; Neurosecretion; Pioneers; Roots
    DOI:  https://doi.org/10.1007/s00441-024-03928-0
  4. Neural Regen Res. 2025 Jan 29.
    Recent advances in immunotherapy targeting amyloid-beta and tauopathies in Alzheimer's disease.
    Sha Sha, Lina Ren, Xiaona Xing, Wanshu Guo, Yan Wang, Ying Li, Yunpeng Cao, Le Qu.
       ABSTRACT: Alzheimer's disease, a devastating neurodegenerative disorder, is characterized by progressive cognitive decline, primarily due to amyloid-beta protein deposition and tau protein phosphorylation. Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer's disease. Conventional drugs, such as donepezil, can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline. Currently, active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer's disease and other transgenic animal models, attracting considerable attention. However, the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab. This review first discusses the advancements in the pathogenesis of Alzheimer's disease and active and passive immunotherapies targeting amyloid-beta and tau proteins. Furthermore, it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects. Although some antibodies have shown promise in patients with mild Alzheimer's disease, substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer's disease.
    DOI:  https://doi.org/10.4103/NRR.NRR-D-24-00846
  5. Am J Pathol. 2025 Jan 23. pii: S0002-9440(25)00027-6. [Epub ahead of print]
    Brain connectivity, neural networks, and resilience in aging and neurodegeneration.
    Diego Szczupak, Lovisa LjungQvist Brinson, Christi L Kolarcik.
      The importance of complex systems has become increasingly evident in recent years. The nervous system is one such example with neural networks sitting at the intersection of complex networks and biology. A particularly exciting feature is the resilience of complex systems. For example, the ability of the nervous system to perform even in the face of challenges that include neuronal loss, neuroinflammation, protein accumulation, axonal disruptions, and metabolic stress is an intriguing and exciting line of investigation. In neurodegenerative diseases, neural network resilience is responsible for the time between the earliest disease-linked changes and clinical symptom onset and disease diagnosis. In this way, connectivity resilience of neurons within the complex network of cells that make up the nervous system has significant implications. This review provides an overview of relevant concepts related to complex systems with a focus on the connectivity of the nervous system. It discusses the development of the neural network and how a delicate balance determines how this complex system responds to injury with examples illustrating maladaptive plasticity. The review then addresses the implications of these concepts, methods to understand brain connectivity and neural networks, and recent research efforts aimed at understanding neurodegeneration from this perspective. The authors aim to provide foundational knowledge and an overview of current research directions in this evolving and exciting area of neuroscience.
    Keywords:  aging; connectivity; neural network; neurodegeneration; resilience
    DOI:  https://doi.org/10.1016/j.ajpath.2024.12.014
  6. Life Med. 2023 Dec;2(6): lnad045
    A framework of biomarkers for skeletal aging: a consensus statement by the Aging Biomarker Consortium.
    Aging Biomarker Consortium
      The skeleton is an important structural and metabolic organ in human body, while aging is the physiological basis for degenerative skeletal diseases. China has the largest aging population in the world and faces great challenges in preventing and managing diseases related to skeletal aging. To address these challenges, the Aging China Biomarkers Consortium (ABC) has reached an expert consensus on biomarkers of skeletal aging by synthesizing the literature and insights from scientists and clinicians. The consensus provides a comprehensive assessment of biomarkers associated with skeletal aging and proposes a systematic framework that categorizes biomarkers into three dimensions, namely, functional, structural, and humoral dimensions. Within each dimension, the ABC recommended clinical and evidential research-based biomarkers for physiological aging and degenerative pathologies of the skeleton. This expert consensus aims to lay the foundation for future studies to assess the prediction, diagnosis, early warning, and treatment of diseases associated with skeletal aging, with the ultimate goal of improving the skeletal health of elderly populations in China and around the world.
    DOI:  https://doi.org/10.1093/lifemedi/lnad045
  7. Trends Cancer. 2025 Jan 28. pii: S2405-8033(25)00001-9. [Epub ahead of print]
    Cancer evolution: from Darwin to the Extended Evolutionary Synthesis.
    Thomas Savy, Lucy Flanders, Thaneswari Karpanasamy, Min Sun, Marco Gerlinger.
      The fundamental evolutionary nature of cancer has been recognized for decades. Increasingly powerful genetic and single cell sequencing technologies, as well as preclinical models, continue to unravel the evolution of premalignant cells, and progression to metastatic stages and to drug-resistant end-stage disease. Here, we summarize recent advances and distil evolutionary principles and their relevance for the clinic. We reveal how cancer cell and microenvironmental plasticity are intertwined with Darwinian evolution and demonstrate the need for a conceptual framework that integrates these processes. This warrants the adoption of the recently developed Extended Evolutionary Synthesis (EES).
    Keywords:  biomarkers; cancer evolution; cellular plasticity; drug resistance; macroevolution; metastasis; mutagenesis
    DOI:  https://doi.org/10.1016/j.trecan.2025.01.001
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