Ageing - NUS Medical Sciences Cluster

ageing

 Our Mission

The MSC Ageing Programme aims to bring together scientists from a broad range of disciplines to investigate the multifaceted aspects of ageing to provide a more comprehensive understanding of the biology of ageing. Our overall goal is to identify and change the ways in which we age to improve the healthspan and lifespan of the elderly through synergistic basic science and clinical collaborations.

Who We Are

We are an inter-disciplinary group consisting of faculty members and researchers from the basic sciences departments of NUS Medicine. The wide-ranging biological expertise within the team well position us to tackle the mechanisms of ageing through many unique directions to develop novel interventions to prevent and better manage common conditions associated with ageing.

What We Do

Understanding the mechanisms behind ageing is important for treating common diseases of old age as well as shedding light on ways to promote successful ageing (longer and healthier lifespan). Our strategy seeks to identify, understand and manipulate common pathways that modulate ageing in model organisms and then to seek methods for their manipulation in humans. This will pave the way to ameliorate the aging process and increase health during ageing in humans.

At present, our research focus areas cover the seven pillars of ageing (Kennedy et al., 2014 Cell 159(4), 709-713) and include current technology:

  • Epigenetics and molecular pathways of ageing
  • Proteostasis
  • Stem cells and regeneration
  • Metabolism
  • Adaptation to stress
  • Macromolecular damage
  • Inflammation
  • Technology

Our research is supported by shared core facilities within the MSC such as the Neuroscience Phenotyping Core (NPC) and the Memory, Aging & Cognition Centre (MACC), as well as imaging, antibody development, and genome and proteome screening platforms.

The Way Forward

We strive to advance the frontiers of ageing research in Singapore through cutting-edge science by leveraging on the multidimensional cooperation and complementary skills amongst the scientific partners within and outside the cluster, and overseas researchers. This programme aims to pave the way for close collaboration with clinicians to translate what we have learned in the lab to novel interventions in humans for the development of clinical trials and practice recommendations that improve quality and reduce cost of elderly healthcare and promote healthy ageing. We hope to foster and train future scientists to engage in high calibre research in ageing and age-related diseases.

 

Researchers Involved in the MSC Ageing Programme

 

Researcher Department Description of Research
Epigenetics and molecular pathways of ageing
Brian Kennedy
(Facilitator)
Centre for Healthy Ageing/Biochemistry Mechanisms and molecular pathways of ageing (mTOR, Sirtuin etc.), human ageing cohort studies, ageing biomarkers
Barry Halliwell
Biochemistry Mechanisms of ageing in C. elegans and humans. Role of reactive oxygen species and antioxidants in age-related diseases, especially neurodegenerative diseases
Jan Gruber Biochemistry Ageing, age-related diseases, interventions against ageing, C. elegans ageing model
Liang Fengyi Anatomy • Molecular pathways that regulate ageing:
- Sirtuin 2, 5 & 6 in neuronal apoptosis, redox equilibrium, glial differentiation/ cell biology
- Actin cytoskeleton, actin-binding proteins, Rho GTPase pathways and brain ageing
- Multiple C2 domain trans-membrane proteins (MCTP1 and MCTP2) and Ca2+ signalling/equilibrium• Reactive oxygen species and stress resistance:
- sirtuins
- actin cytoskeleton, actin-binding proteins in CNS glia, retinal pigment epithelium (RPE) cells.
- multiple C2 domain trans-membrane proteins (MCTP1 and MCTP2)• Mitochondria and ageing: Sirtuin 5 anti-oxidative, anti-apoptotic functions
Wee-Wei Tee Physiology Epigenetics of ageing and ageing-related diseases
Reshma Taneja Physiology Muscle biology, epigenetics
Sudhakar Jha Biochemistry Epigenetic regulation of TERT expression
Yvonne Tay Biochemistry Post-transcriptional regulatory networks
Caroline Lee Biochemistry Cancer and ageing, genetics and epigenetics of ageing, variations associated with ageing, role of FAT10 in cancer and ageing
Alan Prem Kumar Pharmacology RNA homeostasis and telomere maintenance in ageing
Proteostasis
Esther Wong Centre for Healthy Ageing/Physiology Autophagy, mitophagy and proteostasis in ageing and neurodegeneration
Wang Jigang Centre for Healthy Ageing/Pharmacology Chemical biology, autophagy, ageing
Shen Han-Ming Physiology The autophagy-lysosomal pathway in ageing
Stem cells and regenerative biology
Zeng Xianmin Centre for Healthy Ageing/ Physiology Stem cells in ageing and neurodegeneration
Derrick Ong Physiology Stem cells and regenerative biology, neurodegeneration and cognitive decline, brain ageing, epigenetics and signalling pathways (e.g. calcium signalling), telomere, DNA damage and genomic instability
Metabolism
Nguyen Nam Long Biochemistry Lipids in healthy ageing
Thilo Hagen Biochemistry Study of cell metabolism and how metabolic changes are involved in human diseases
Long Yun Chau Biochemistry Effects of nutrients on growth factor and nutrient signalling including AMPK and mTORC1 pathways
Yew Wen Shan Biochemistry Synthetic enzymology-enabled:
-Metabolism and dietary modulation
-Novel therapeutics interventions and treatment strategies to increase human healthspan
Thiruma Valavan Arumugam Physiology Calorie restriction induced neuroprotection, epigenetics of intermittent fasting and stroke
Adaptation to stress
Goh Jorming Centre for Healthy Ageing/Physiology Exercise and ageing, cancer, immune function
Shazib Pervaiz Physiology Redox metabolism, mitochondria and cell fate signaling
Tsai Shih-Yin Physiology Sarcopenia, mTOR, proteostasis, sex, exercise and ageing
Jason Lee Physiology Thermoregulation and ageing – impact on exercise, nutrition and recovery
Mallilankaraman Karthik Babu Physiology Mitochondrial calcium and redox signalling, mitochondrial dysfunction in neurodegenerative and metabolic diseases
Ang Eng Tat Anatomy Tai Chi research and ageing
Marie-Veronique Clement Biochemistry Redox regulation of the senescent phenotype
Deng Lih Wen Biochemistry Reactive oxygen species and stress resistance, metabolism and dietary modulation
Lim Yun-An (Andrea) Pharmacology Neurodegeneration and cognitive decline, inflammation, mitochondria and ageing, reactive oxygen species
Macromolecular damage
Manoor Prakash Hande Physiology Telomeres, telomerase, DNA damage/repair, genome stability
Ling Shuo-Chien Physiology Ageing and age-dependent neurodegeneration
John Chua Jia En Physiology Neurodegeneration and neuronal ageing
Soong Tuck wah Physiology Calcium channels in brain health and aging, autophagy and lysosomes
Sajikumar Sreedharan Physiology Long-term memory, dementia, neurodegeneration and cognitive decline, brain ageing and epigenetics and signalling pathways
Sanjay Khanna Physiology The neural basis of affect-motivation and co-morbid disorder of cognition and mood in chronic pain
Dheen S.Thameem Anatomy • Molecular and epigenetic characterization of microglial cells and development of strategies to inhibit microglia-mediated neuroinflammation in neuropathological conditions (neurodegeneration and brain injury).
• Unravelling the mechanisms of microglia-mediated cognitive processes in aging brain. It is hypothesized that memory molecules expressed in microglia are involved in cognitive processes including synaptic plasticity and contribute to age-related cognitive decline.
Study of maternal diabetes induced changes in the epigenomic landscape of genes involved in neurodevelopmental processes such as axon guidance, corticogenesis and synaptogenesis predisposing offspring to Autism Spectrum Disorder
Ong Wei Yi Anatomy Neurodegeneration and cognitive decline, reactive oxygen species and stress resistance, brain ageing, inflammation, epigenetics and signalling pathways (e.g. calcium signalling), develop and test novel therapeutics interventions and treatment strategies designed to increase human healthspan
Deron Raymond Herr Pharmacology
Gavin Stewart Dawe Pharmacology Amyloid precursor protein (APP) signaling and mitochondrial peptides in neurodegenerative disease and ageing; neurogenesis, brain circuitry, neuropeptide pharmacology in modulation of plasticity and cognitive and emotional function in dementia and ageing
Jiang Jianming Biochemistry/ Cardiovascular Research Institute (CVRI) DNA damage response in ageing and dilated cardiomyopathy
Inflammation
Lim Hsiu Kim Lina Physiology Stress and ageing, inflammatory biomarkers for ageing
Herbert Schwarz Physiology Effect of mitochondria-targeting compounds SS-31 and PZ19b on immune ageing and exhaustion. Exploring the underlying mechanism and feasibility of therapeutic interference to ameliorate age-related inflammation by CD137
Celestial Yap Physiology Cytoskeleton and Tumour Biology, signalling pathways in cancer and inflammatory diseases
Nicholas Gascoigne Microbiology and Immunology T cell development, differentiation, and activation, thymus regeneration.
Alonso Sylvie Microbiology and Immunology Host pathogen interactions (dengue, HFMD, tuberculosis, flu), mouse models of infectious diseases, vaccine development
Liu Haiyan Microbiology and Immunology Cancer immunotherapy and ageing
Benoit Malleret Microbiology and Immunology Erythrocytic immunobiology
Lu Jinhua Microbiology and Immunology • C1q is produced by macrophages and dendritic cells and an elevated biomarker, together with CRP, IL6 and IL1, and accelerates fibroblastic differentiation of muscle cells. We screened FDA/natural product chemical libraries and identified candidates that regulate C1q production by macrophages (molecular pathways that regulate ageing).

• We work with antinuclear autoantibodies (ANA) which increase in elderly individuals and can contribute to the elevate inflammatory status in the aged group (inflammation). We work with a broad spectrum of nuclear antigens and are generating natural autoantibodies that help reduce the inflammatory status.

• We work with nucleoli and ribosome biogenesis – the rRNA genes are sequestered on the five acrocentric chromosomes close to the telomeres and abnormality in ribosome gene transcription/ribosome production can lead to cellular senescence and genomic instability (telomere, DNA damage and genomic instability).

Justin Chu Microbiology and Immunology • Ageing and dengue infection
• Ageing and virome
Angeli Veronique Microbiology and Immunology Contribution of tissue resident macrophages in ageing: recently we identified a population of resident tissue macrophage expressing hyaluronan receptor LYVE-1. This population of macrophage is found in all vascularised tissues and a subpopulation of LYVE-1+ macrophage specifically lines the outer layer of large blood vessels such as the aorta. RNA sequencing revealed that LYVE-1+ macrophages are involved in tissue homeostatic functions compared to LYVE-1 macrophages that have more immunological functions. In line with this finding, we demonstrated the critical role of LYVE-1+ macrophages in preventing arterial stiffness by controlling extracellular matrix 9ECM) remodelling in arterial wall. We are now investigating their contribution in ageing-related arterial stiffness, a hallmark of vascular ageing and a risk factor for cardiovascular diseases. Our research is not limited to vasculature but extended to skin and skeletal muscles as LYVE-1+ are abundant in these tissues and seem to control ECM homeostasis. Therefore, they may also be involved in skin ageing and sarcopenia.
Zhang Yongliang Microbiology and Immunology Inflammatory signalling in ageing-associated metabolic disorders
Tan Yee Joo Microbiology and Immunology Immunity and infection (virology)
George Yip Anatomy Cancers, cell death and cellular senescence, molecular pathways that regulate ageing (e.g. TOR, Sirtuin)
Bay Boon Huat Anatomy Cancers, cell death and cellular senescence
Mitchell Lai Pharmacology Dementia, Biomarkers, Neuroinflammation, neurochemistry, neurotransmission
Fred Wong Pharmacology Asthma, COPD, inflammation, antioxidants, natural products
Technology
Jonathan Scolnick Physiology Single cell proteogenomic technology development
Volker Patzel Microbiology and Immunology RNA trans-splicing based suicide gene therapy approach, development of an efficient, modular, and scalable mitochondrial delivery vector system for nucleic acids

Adjunct Members

Researcher Department Description of Research
Feng Lei Psychological Medicine NUS Cohort-based studies of healthy ageing, phenotypes, markers and determinants of cognitive ageing, prevention of cognitive decline and dementia, nutrition and phytonutrients in brain health
Tong-Wey Koh Temasek Life Sciences Laboratory Ageing and neurodegeneration, short-living model organisms: fruitfly and African turquoise killifish
Anis Larbis Singapore Immunology Network, A*STAR Immune robustness and healthspan, Inflamm-aging, T-cells
Colin Stewart Institute of Medical Biology, Physiology NUS Vascular ageing, atherosclerosis, Progeria and muscle regeneration

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