Neurological Diseases, Intermittent Fasting and Exosomes

ARUMUGAM, Thiruma Valavan Centre for Cardiovascular Biology and Disease Research, La Trobe University, Melbourne, Australia

Abstract：As the brain ages, it undergoes significant cellular changes that indicate compromised bioenergetics, impaired neuroplasticity, disrupted resilience, aberrant neuronal network activity, dysregulated Ca2+ homeostasis, accumulation of oxidatively modified molecules and organelles, and increased inflammation. These alterations make the aging brain vulnerable to neurodegenerative conditions, including Alzheimer's and Parkinson's diseases, vascular dementia, and stroke. Intermittent fasting (IF), a dietary regimen that alternates between periods of unrestricted food intake and fasting without sacrificing nutritional quality, has shown promise in promoting longevity and mitigating the development of age-related dementia. Our findings demonstrate that IF induces changes in chromosome accessibility, epigenomic landscape, RNA, and protein profiles, orchestrating extensive alterations in gene expression compared to ad libitum feeding. This discovery may pave the way for a paradigm shift in using IF as a universally accessible, drug-free preventive lifestyle management strategy.

BIO：Professor Arumugam obtained his Bachelor's Degree in Medical Science with Honors from the University of Sydney in 1998 and a Doctor of Philosophy in Pharmacology from the University of Queensland in 2003. He completed post-doctoral training at Louisiana State University Health Sciences Center and at the National Institute of Health, Baltimore, under Professor Mark Mattson. He established his independent laboratory at Texas Tech University Health Sciences Center in 2007, later transitioning to The University of Queensland, the National University of Singapore, and joining La Trobe University in March 2020. His research is primarily dedicated to unraveling neuronal cell death mechanisms in stroke and vascular dementia and exploring the impact of intermittent metabolic switching on brain aging. His contributions have appeared in journals such as Nature Medicine, Nature Neuroscience, Circulation, PNAS, Molecular Psychiatry, Theranostics, Cell Metabolism, and Nature Communications, with over 195 articles, more than 23,000 citations, and an h-index of 79.

JO, Dong-Gyu School of Pharmacy, Sungkyunkwan University, Seoul, Korea

Abstract：Effective intracellular delivery of therapeutic proteins can potentially treat a wide array of diseases, yet efficient delivery across the cell membrane remains challenging. We engineered exosomes equipped with a photoinducible cargo protein release system (MAPLEX), in which cargo proteins are loaded by fusing them with photocleavable protein (mMaple3)–conjugated exosomal membrane markers and released by blue-light illumination. Using this system, we induced transcriptional regulation in fibroblasts, in vivo gene recombination in Cre reporter mice, and targeted epigenome editing in the brains of 5xFAD and 3xTg-AD Alzheimer's models. Delivery of Bace1-targeting dCas9 ribonucleoprotein complexes with the catalytic domain of DNMT3A methylated targeted CpG sites within the Bace1 promoter, reducing Bace1 expression, improving recognition memory, and reducing amyloid pathology.

BIO：Dong-Gyu Jo is a Professor of the School of Pharmacy at Sungkyunkwan University. He received his Ph.D. in Molecular Neurobiology from the Gwangju Institute of Science & Technology in 2002, and from 2003 to 2007 worked in the Laboratory of Neurosciences at the National Institute on Aging, NIH, USA, as a postdoctoral fellow. In 2007 he started his own laboratory at Sungkyunkwan University. His laboratory employs experimental models of aging and age-related neurodegenerative disorders to establish the cellular and biochemical changes occurring during aging and in disorders such as Alzheimer's, Parkinson's, and stroke, and runs drug discovery projects. Recently his research interests have expanded to the field of extracellular vesicles.

LAI, Mitchell K.P. Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore

Abstract：Alzheimer's disease (AD) and vascular dementia (VaD) remain two of the commonest causes of dementia in the elderly, and represent unmet needs in terms of efficient, early diagnosis, disease-modifying treatments, and prevention. In this talk, I showcase my lab's efforts in characterizing AD and VaD using proteomic and lipidomic approaches. I also introduce the concept of cognitive resilience (CR) in the context of cognitive decline and dementia, and how knowledge gained from intermittent fasting studies may inform identification and amplification of CR targets as a potential strategy to preserve cognitive function or even reverse the dementia process.

BIO：LAI, Kim Peng Mitchell（赖君鹏）obtained his BSc in Biological Sciences from the University of Alberta, Canada, and PhD in Medicine from the University of Sydney, Australia. He was Principal Research Scientist at the Department of Clinical Research, Singapore General Hospital, and Visiting Senior Fellow at the Wolfson Centre for Age-Related Diseases, King's College London, before moving to the Yong Loo Lin School of Medicine, National University of Singapore, where he is now Senior Lecturer and Education Director with the Department of Pharmacology, and Principal Investigator with the Memory, Ageing and Cognition Centre. His research interest is in dementia, specifically identification of novel drug targets and biomarkers for Alzheimer's disease and vascular dementia. He has authored over 100 research articles and several book chapters.

CHEN, Guobin School of Medicine, Jinan University

Abstract：Aging Research is an Open Access publication addressing the biology and medicine issues of aging and aging-related diseases. The journal publishes original research of unusual significance or broad conceptual or technical advances in all areas of aging, longevity and aging-related health issues, exploring the process, mechanism, biomarkers, anti-aging strategies or drugs at the population, individual, system, organ, tissue, cell and subcellular levels.

BIO：Guobing Chen is Professor of Immunology, Director of Institute of Geriatric Immunology and Dean of the School of Medicine, Jinan University in China. His group is working on how the immune system changes during aging, to identify the biomarkers of immune aging, explore the immunological factors relevant to geriatric diseases such as infectious, autoimmune and neurodegenerative diseases, and to develop efficient treatments to prevent aging and aging-related diseases.