bims-agimec 2025-02-23 papers

Issue of 2025–02–23
seven papers selected by
Metin Sökmen, Ankara Üniversitesi

J Parkinsons Dis. 2025 Feb 02. 1877718X251316552

Aging, cellular senescence and Parkinson's disease.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, affecting 1-2% of people over age 65. The risk of developing PD dramatically increases with advanced age, indicating that aging is likely a driving factor in PD neuropathogenesis. Several age-associated biological changes are also hallmarks of PD neuropathology, including mitochondrial dysfunction, oxidative stress, and neuroinflammation. Accumulation of senescent cells is an important feature of aging that contributes to age-related diseases. How age-related cellular senescence affects brain health and whether this phenomenon contributes to neuropathogenesis in PD is not yet fully understood. In this review, we highlight hallmarks of aging, including mitochondrial dysfunction, loss of proteostasis, genomic instability and telomere attrition in relation to well established PD neuropathological pathways. We then discuss the hallmarks of cellular senescence in the context of neuroscience and review studies that directly examine cellular senescence in PD. Studying senescence in PD presents challenges and holds promise for advancing our understanding of disease mechanisms, which could contribute to the development of effective disease-modifying therapeutics. Targeting senescent cells or modulating the senescence-associated secretory phenotype (SASP) in PD requires a comprehensive understanding of the complex relationship between PD pathogenesis and cellular senescence.

Keywords: Parkinson's disease; aging; cellular senescence; neurodegeneration; senolytic

DOI: https://doi.org/10.1177/1877718X251316552

Aging Dis. 2025 Feb 11.

Ovarian Aging: The Silent Catalyst of Age-Related Disorders in Female Body.

Xingyu Liu, Yuanqu Zhao, Yanzhi Feng, Shixuan Wang, Aiyue Luo, Jinjin Zhang.

Age-related diseases have emerged as a global concern as the population ages. Consequently, understanding the underlying causes of aging and exploring potential anti-aging interventions is imperative. In females, the ovaries serve as the principal organs responsible for ovulation and the production of female hormones. The aging ovaries are related to infertility, menopause, and associated menopausal syndromes, with menopause representing the culmination of ovarian aging. Current evidence indicates that ovarian aging may contribute to dysfunction across multiple organ systems, including, but not limited to, cognitive impairment, osteoporosis, and cardiovascular disease. Nevertheless, due to the widespread distribution of sex hormone receptors throughout the body, ovarian aging affects not only these specific organs but also influences a broader spectrum of age-related diseases in women. Despite this, the impact of ovarian aging on overall age-related diseases has been largely neglected. This review provides a thorough summary of the impact of ovarian aging on age-related diseases, encompassing the nervous, circulatory, locomotor, urinary, digestive, respiratory, and endocrine systems. Additionally, we have outlined prospective therapeutic approaches for addressing both ovarian aging and age-related diseases, with the aim of mitigating their impacts and preserving women's fertility, physical health, and psychological well-being.

DOI: https://doi.org/10.14336/AD.2024.1468

Aging Dis. 2025 Feb 17.

The Role of Hypoxia in Longevity.

Ayesha Nisar, Sawar Khan, Yongzhang Pan, Li Hu, Pengyun Yang, Naheemat Modupeola Gold, Zhen Zhou, Shengjie Yuan, Meiting Zi, Sardar Azhar Mehmood, Yonghan He.

Aging is marked by a progressive decrease in physiological function and reserve capacity, which results in increased susceptibility to diseases. Understanding the mechanisms of driving aging is crucial for extending health span and promoting human longevity. Hypoxia, marked by reduced oxygen availability, has emerged as a promising area of study within aging research. This review explores recent findings on the potential of oxygen restriction to promote healthy aging and extend lifespan. While the role of hypoxia-inducible factor 1 (HIF-1) in cellular responses to hypoxia is well-established, its impact on lifespan remains complex and context-dependent. Investigations in invertebrate models suggest a role for HIF-1 in longevity, while evidence in mammalian models is limited. Hypoxia extends the lifespan independent of dietary restriction (DR), a known intervention underlying longevity. However, both hypoxia and DR converge on common downstream effectors, such as forkhead box O (FOXO) and flavin-containing monooxygenase (FMOs) to modulate the lifespan. Further work is required to elucidate the molecular mechanisms underlying hypoxia-induced longevity and optimize clinical applications. Understanding the crosstalk between HIF-1 and other longevity-associated pathways is crucial for developing interventions to enhance lifespan and healthspan. Future studies may uncover novel therapeutic strategies to promote healthy aging and longevity in human populations.

DOI: https://doi.org/10.14336/AD.2024.1630

Hum Cell. 2025 Feb 19. 38(2): 58

Extrachromosomal circular DNA: a double-edged sword in cancer progression and age-related diseases.

Shadira Anindieta Irdianto, Astari Dwiranti, Anom Bowolaksono.

Extrachromosomal circular DNA (eccDNA) is a fascinating form of genetic material found outside the usual chromosomal DNA in eukaryotic cells, including humans. Since its discovery in the 1960s, eccDNA has been linked to critical roles in cancer progression and age-related diseases. This review thoroughly explores eccDNA, covering its types, how it forms, and its significant impact on diseases, particularly cancer. EccDNA, especially in its extrachromosomal DNA (ecDNA) form, contributes to the genetic diversity of tumour cells, helping them evolve quickly and resist treatments. Beyond cancer, eccDNA is also connected to age-related conditions like Werner syndrome, amyotrophic lateral sclerosis (ALS), and type 2 diabetes mellitus (T2DM), where it may affect genomic stability and disease development. The potential of eccDNA as a biomarker for predicting disease outcomes and as a target for new treatments is also highlighted. This review aims to deepen our understanding of eccDNA and inspire further research into its roles in human health and disease, paving the way for innovative diagnostic and therapeutic approaches.

Keywords: Ageing; Biomarker; Cancer; Extrachromosomal circular DNA; Gene amplification

DOI: https://doi.org/10.1007/s13577-025-01178-y

Nat Rev Cardiol. 2025 Feb 19.

Roadmap for alleviating the manifestations of ageing in the cardiovascular system.

Luca Liberale, Simon Tual-Chalot, Simon Sedej, Stefano Ministrini, Georgios Georgiopoulos, Myriam Grunewald, Magnus Bäck, Marie-Luce Bochaton-Piallat, Reinier A Boon, Gustavo Campos Ramos, Menno P J de Winther, Konstantinos Drosatos, Paul C Evans, Jane F Ferguson, Sofia K Forslund-Startceva, Claudia Goettsch, Mauro Giacca, Judith Haendeler, Marinos Kallikourdis, Daniel F J Ketelhuth, Rory R Koenen, Patrick Lacolley, Esther Lutgens, Pasquale Maffia, Satomi Miwa, Claudia Monaco, Fabrizio Montecucco, Giuseppe Danilo Norata, Elena Osto, Gavin D Richardson, Niels P Riksen, Oliver Soehnlein, Ioakim Spyridopoulos, Sophie Van Linthout, Gemma Vilahur, Jolanda J Wentzel, Vicente Andrés, Lina Badimon, Athanase Benetos, Christoph J Binder, Ralf P Brandes, Filippo Crea, David Furman, Vera Gorbunova, Tomasz J Guzik, Joseph A Hill, Thomas F Lüscher, María Mittelbrunn, Alessio Nencioni, Mihai G Netea, João F Passos, Kimon S Stamatelopoulos, Nektarios Tavernarakis, Zoltan Ungvari, Joseph C Wu, James L Kirkland, Giovanni G Camici, Stefanie Dimmeler, Guido Kroemer, Mahmoud Abdellatif, Konstantinos Stellos.

Ageing of the cardiovascular system is associated with frailty and various life-threatening diseases. As global populations grow older, age-related conditions increasingly determine healthspan and lifespan. The circulatory system not only supplies nutrients and oxygen to all tissues of the human body and removes by-products but also builds the largest interorgan communication network, thereby serving as a gatekeeper for healthy ageing. Therefore, elucidating organ-specific and cell-specific ageing mechanisms that compromise circulatory system functions could have the potential to prevent or ameliorate age-related cardiovascular diseases. In support of this concept, emerging evidence suggests that targeting the circulatory system might restore organ function. In this Roadmap, we delve into the organ-specific and cell-specific mechanisms that underlie ageing-related changes in the cardiovascular system. We raise unanswered questions regarding the optimal design of clinical trials, in which markers of biological ageing in humans could be assessed. We provide guidance for the development of gerotherapeutics, which will rely on the technological progress of the diagnostic toolbox to measure residual risk in elderly individuals. A major challenge in the quest to discover interventions that delay age-related conditions in humans is to identify molecular switches that can delay the onset of ageing changes. To overcome this roadblock, future clinical trials need to provide evidence that gerotherapeutics directly affect one or several hallmarks of ageing in such a manner as to delay, prevent, alleviate or treat age-associated dysfunction and diseases.

DOI: https://doi.org/10.1038/s41569-025-01130-5

J Physiol Biochem. 2025 Feb 19.

The link between Mitochondria and Sarcopenia.

Nurul Tihani Kamarulzaman, Suzana Makpol.

Sarcopenia, a widespread condition, is characterized by a variety of factors influencing its development. The causes of sarcopenia differ depending on the age of the individual. It is defined as the combination of decreased muscle mass and impaired muscle function, primarily observed in association with ageing. As people age from 20 to 80 years old, there is an approximate 30% reduction in muscle mass and a 20% decline in cross-sectional area. This decline is attributed to a decrease in the size and number of muscle fibres. The regression of muscle mass and strength increases the risk of fractures, frailty, reduced quality of life, and loss of independence. Muscle cells, fibres, and tissues shrink, resulting in diminished muscle power, volume, and strength in major muscle groups. One prominent theory of cellular ageing posits a strong positive relationship between age and oxidative damage. Heightened oxidative stress leads to early-onset sarcopenia, characterized by neuromuscular innervation breakdown, muscle atrophy, and dysfunctional mitochondrial muscles. Ageing muscles generate more reactive oxygen species (ROS), and experience decreased oxygen consumption and ATP synthesis compared to younger muscles. Additionally, changes in mitochondrial protein interactions, cristae structure, and networks may contribute to ADP insensitivity, which ultimately leads to sarcopenia. Within this framework, this review provides a comprehensive summary of our current understanding of the role of mitochondria in sarcopenia and other muscle degenerative diseases, highlighting the crucial need for further research in these areas.

Keywords: Mitochondria; Mitochondrial protein interactions; Muscle ageing; Oxidative stress; Sarcopenia

DOI: https://doi.org/10.1007/s13105-024-01062-7

Neurochem Int. 2025 Feb 14. pii: S0197-0186(25)00020-8. [Epub ahead of print]184 105947

Beyond plaques and tangles: The role of immune cell dysfunction in Alzheimer's disease.

Nasif Hussain, Mohd Moin Khan, Ayushi Sharma, Rakesh K Singh, Rizwan Hasan Khan.

The interplay between immune cell dysfunction and associated neuroinflammation plays a critical role in the pathogenesis of Alzheimer's disease. Neuroinflammation, orchestrated by microglia and peripheral immune cells, exacerbates synaptic dysfunction and neurodegeneration in AD. Emerging evidence suggests a systemic immune response in AD, challenging traditional views of neurocentric pathology. Therapeutic strategies targeting neuroinflammation hold promise, yet translating preclinical findings into clinical success remains elusive. This article presents recent advances in AD scientific studies, highlighting the pivotal role of immune cell dysfunction and signaling pathways in disease progression. We also discussed therapeutic studies targeting immune cell dysregulation, as treatment methods. This advocates for a paradigm shift towards holistic approaches that integrate peripheral and central immune responses, fostering a comprehensive understanding of AD pathophysiology and paving the way for transformative interventions.

Keywords: Alzheimer's disease; Aβ; Immune system; Immunotherapy; Microglia; Neurodegeneration; T cells

DOI: https://doi.org/10.1016/j.neuint.2025.105947