bims-agimec 2024-12-22 papers

Issue of 2024–12–22
seven papers selected by
Metin Sökmen, Ankara Üniversitesi

Cell Mol Biol Lett. 2024 Dec 18. 29(1): 153

Inter- and intracellular mitochondrial communication: signaling hubs in aging and age-related diseases.

Meng Zhang, Jin Wei, Chang He, Liutao Sui, Chucheng Jiao, Xiaoyan Zhu, Xudong Pan.

Mitochondria are versatile and complex organelles that can continuously communicate and interact with the cellular milieu. Deregulated communication between mitochondria and host cells/organelles has significant consequences and is an underlying factor of many pathophysiological conditions, including the process of aging. During aging, mitochondria lose function, and mitocellular communication pathways break down; mitochondrial dysfunction interacts with mitochondrial dyscommunication, forming a vicious circle. Therefore, strategies to protect mitochondrial function and promote effective communication of mitochondria can increase healthy lifespan and longevity, which might be a new treatment paradigm for age-related disorders. In this review, we comprehensively discuss the signal transduction mechanisms of inter- and intracellular mitochondrial communication, as well as the interactions between mitochondrial communication and the hallmarks of aging. This review emphasizes the indispensable position of inter- and intracellular mitochondrial communication in the aging process of organisms, which is crucial as the cellular signaling hubs. In addition, we also specifically focus on the status of mitochondria-targeted interventions to provide potential therapeutic targets for age-related diseases.

Keywords: Age-related diseases; Aging; Mitochondrial communication; Mitochondrial dysfunction; Signaling hubs

DOI: https://doi.org/10.1186/s11658-024-00669-4

AAPS PharmSciTech. 2024 Dec 19. 26(1): 17

Gene Therapy: Towards a New Era of Medicine.

Mokshit Bhagat, Raj Kamal, Jyoti Sharma, Kirandeep Kaur, Amit Sharma, Gurjeet Singh Thakur, Rohit Bhatia, Ankit Awasthi.

Over the past years, many significant advances have been made in the field of gene therapy and shown promising results in clinical trials conducted. Gene therapy aims at modifying or replacing a defective, inefficient, or nonfunctional gene with a healthy, functional gene by administration of genome material into the cell to cure genetic diseases. Various methods have been devised to do this by using several viral and non-viral vectors which are either administered by in vivo or ex vivo technique. Viral vectors are best suitable for this therapy due to their potential to invade cells and deliver their genetic material whereas non-viral vectors are less efficient than viral vectors but possess some advantages such as less immunogenic response and large gene carrying capacity. Recent advances in biotechnology such as CRISPR-Cas9 mediated genome engineering and Cancer treatment with Chimeric antigen receptor (CAR) T-cell therapy are addressed in this review. This review article also delves into some recent research studies, gene therapy trials, and its applications, laying out future hopes for gene therapy in the treatment of various diseases namely haemophilia, Muscular dystrophy, SCID, Sickle cell disease, Familial Hypercholesterolemia, Cystic Fibrosis. Additionally, it also includes various nanoformulations and clinical trial data related to gene therapy.

Keywords: CAR T-cell; CRISPR-Cas9; gene therapy; gene vectors; genetic disease; viral vectors

DOI: https://doi.org/10.1208/s12249-024-03010-6

Ther Adv Rare Dis. 2024 Jan-Dec;5:5 26330040241305144

Hutchinson-Gilford progeria syndrome: unraveling the genetic basis, symptoms, and advancements in therapeutic approaches.

Akhil Arun, Athira Rejith Nath, Bonny Thankachan, M K Unnikrishnan.

Hutchinson-Gilford Progeria syndrome (HGPS) serves as a prominent model for Progeroid syndromes, a group of rare genetic disorders characterized by accelerated aging. This review explores the genetic basis, clinical presentation, and complications of HGPS. HGPS is caused by mutations in the LMNA gene, resulting in the production of a defective structural protein, prelamin A. This protein contains a "CAAX" motif, where C represents cysteine, and its abnormal processing is central to the disease's pathology. HGPS leads to multiple organ systems being affected, including cardiovascular, skeletal, neurological, and dermatological systems, causing severe disability and increased mortality. Cardiovascular issues are particularly significant in HGPS and are crucial for developing therapeutic strategies. Recent advances in treatment modalities offer promise for managing HGPS. Farnesyltransferase inhibitors and genetic interventions, such as CRISPR-Cas9, have shown potential in mitigating progerin-associated symptoms, with encouraging results observed in preclinical and clinical studies. Additionally, emerging therapies such as rapamycin, sulforaphane, and MG132 hold promise in targeting underlying disease mechanisms. Comprehensive management approaches, including growth hormone therapy, retinoids, and dental care, are emphasized to enhance overall patient well-being. Despite progress, further research is essential to unravel the complex pathophysiology of Progeroid syndromes and develop effective treatments. Continued focus on therapies that address progerin accumulation and its downstream effects is vital for improving patient care and outcomes for individuals affected by HGPS and related disorders. This review highlights ongoing efforts to understand and combat Progeroid syndromes, aiming to alleviate the burdens imposed by these debilitating conditions.

Keywords: Hutchinson–Gilford progeria syndrome; accelerated aging; farnesyltransferase; lamin A; progerin therapy; rare diseases

DOI: https://doi.org/10.1177/26330040241305144

NPJ Metab Health Dis. 2024 ;2(1): 37

Too old for healthy aging? Exploring age limits of longevity treatments.

Prerana Shrikant Chaudhari, Maria A Ermolaeva.

It is well documented that aging elicits metabolic failures, while poor metabolism contributes to accelerated aging. Metabolism in general, and energy metabolism in particular are also effective entry points for interventions that extend lifespan and improve organ function during aging. In this review, we discuss common metabolic remedies for healthy aging from the angle of their potential age-specificity. We demonstrate that some well-known metabolic treatments are mostly effective in young and middle-aged organisms, while others maintain high efficacy independently of age. The mechanistic basis of presence or lack of the age limitations is laid out and discussed.

Keywords: Energy metabolism; Metabolism; Mitochondria; Physiology

DOI: https://doi.org/10.1038/s44324-024-00040-3

Regen Ther. 2025 Mar;28 12-19

Research of in vivo reprogramming toward clinical applications in regenerative medicine: A concise review.

Yoshihiko Nakatsukasa, Yosuke Yamada, Yasuhiro Yamada.

The successful generation of induced pluripotent stem cells (iPSCs) has significantly impacted many scientific fields. In the field of regenerative medicine, iPSC-derived somatic cells are expected to recover impaired organ functions through cell transplantation therapy. Subsequent studies using genetically engineered mouse models showed that somatic cells are also reprogrammable in vivo. Notably, cyclic expression of reprogramming factors, so-called partial reprogramming in vivo ameliorates cellular and physiological hallmarks of aging without inducing teratoma formation or premature death of animals. Subsequent studies provided evidence supporting the beneficial effects of partial reprogramming in various organs. Although in vivo reprogramming appears to be a promising strategy for tissue regeneration and rejuvenation, there remain unsolved issues that hinder its clinical application, including concerns regarding its safety, controllability, and unexpected detrimental effects. Here, we review the pathway that research of in vivo reprogramming has followed and discuss the future perspective as we look toward its clinical application in regenerative medicine.

Keywords: Induced pluripotent stem cells; In vivo reprogramming; Regeneration; Regenerative medicine; Rejuvenation

DOI: https://doi.org/10.1016/j.reth.2024.11.008

Subcell Biochem. 2024 ;107 91-116

Unlocking the Potential of Senolytic Compounds: Advancements, Opportunities, and Challenges in Ageing-Related Research.

Lilian Sales Gomez, Diana Jurk.

Cellular senescence is recognised as a contributor to the ageing process and the development of multiple age-related conditions. Researchers have launched efforts to identify compounds capable to selectively kill senescent cells, known as senolytics, without affecting non senescent cells. As of now, over 40 compounds have demonstrated senolytic properties, offering promising prospects for reversing or ameliorating age-related conditions in preclinical studies.This chapter presents the most recent developments in senolytic drug research, encompassing investigations spanning basic science, preclinical trials, and clinical studies. While many of these investigations have generated encouraging results in the realm of age-related interventions, this chapter also addresses potential challenges and pitfalls.

Keywords: Age-related diseases; Ageing; Cellular senescence; Senolytic

DOI: https://doi.org/10.1007/978-3-031-66768-8_5

Subcell Biochem. 2024 ;107 245-268

Role of Vitamin B in Healthy Ageing and Disease.

Kathleen Mikkelsen, Maria Trapali, Vasso Apostolopoulos.

B vitamin complex consist of vitamins B1, B2, B5, B6, B9, B12 and is pivotal for overall health, influencing vital functions such as, energy metabolism, DNA maintenance, and healthy immune system. Inadequate B vitamin levels are associated with various health issues, including neurocognitive problems, immune imbalances, and inflammation. In ageing individuals, deficiencies in B vitamins increase the risk of cardiovascular ailments, stroke, cognitive disorders, neurodegeneration, mental health issues, and methylation-related disorders. These result primarily due to changes in glycation, mitochondria, and oxidative stress. Thus, ensuring optimal vitamin B levels in the ageing population may be beneficial in preventing such age-related diseases. In this chapter we discuss the extensive role of B vitamins in the ageing process.

Keywords: Ageing; Cobalamin; Folate; Niacin; Pyridoxine; Riboflavin; Thiamine; Vitamin B

DOI: https://doi.org/10.1007/978-3-031-66768-8_12