Ageing &
Brain Health
Multiple Sclerosis is most commonly diagnosed in young adults, but it is a chronic condition that people live with as they get older. Increasing age is associated with worse recovery after relapses, reduced benefit from disease-modifying therapies and a higher chance of progressive disease. Older patients are also more likely to have other medical conditions and medications, both of which can interact with their MS.
Dr Chris McMurran and Dr Jonathon Holland were awarded the 2024 Vera Down grant to support research into ageing and brain repair in MS. In the video below, they discuss the research that this funding will support.
AGE & REMYELINATION
Damage to the myelin sheaths around nerve fibres can be repaired in a regenerative process called remyelination. However, much like wound healing in the skin, this repair process becomes less effective as people get older. In the CCMR One trial, we showed that the response to the remyelinating drug bexarotene was strongest in patients under the age of 42 (McMurran… Cunniffe, 2022, Ann Clin Transl Neurol.).
This result aligns with laboratory studies that have demonstrated problems in the oligodendrocyte progenitor cells, the immune response and the efficiency of remyelination in older animals.
Our systematic review of ageing and remyelination, led by Dr Trisha Mukherjee, was recently published in the journal Brain.
Age-related decline in remyelination is thought to be an important driver for secondary neuronal loss and increasing disability as people with MS get older. We are investigating this hypothesis in the ARMOUR-MS study. In this observational cohort study, people with MS across the lifespan from childhood to old age have their myelin dynamics and axonal health mapped over time using visual assessments, MRI, clinical scores and blood biomarkers.
The treatment effect of bexarotene on VEP latency improvement (a biomarker for remyelination) reduces with increasing chronological age. From McMurran et al., 2022.
BIOLOGICAL AGEING
Ageing is more than the simple passage of time. It is mediated by biological processes that vary between individuals due to genetic and environmental influences. The idea that people can age at different rates is a concept known as biological ageing. For example, two people aged 40 may show biological profiles more typical of age 20 and 60 respectively, reflecting differences in their physiology and disease risk.
Many different approaches exist to measure biological age, including the use of clinical blood test results, DNA methylation patterns or volumetric brain MRI data. We have shown that for two healthy people with the same chronological age, an older blood- or methylation-based biological increases the risk of developing various neurological conditions in the future (McMurran et al., 2023, Brain; Mak & McMurran et al., 2023, JNNP).
Our research aims to understand the relationship between remyelination, neuronal loss and biological ageing in people with MS. We do this by generating different measures of biological age in our clinical cohorts and linking these to remyelination outcomes.
Understanding the interaction between biological age and MS could lead to more accurate prognostic information for people with MS. Additionally, a growing class geroprotective drugs aims to target the biological mechanisms that drive ageing. These interventions hold promise as a means to delay or prevent problems that people with MS face as they get older.
GEROPROTECTIVE DRUGS IN MS
Our recently completed CCMR Two trial showed that the combination of metformin and clemastine can promote remyelination in people with relapsing remitting MS. The study tested a novel concept: whether an intervention that targets the underlying mechanisms of ageing can boost remyelination and neuronal protection in humans.
Metformin is an oral diabetes medication that has an evidence base as a geroprotective drug: it can slow or postpone multiple age-related pathologies in laboratory models, as well as in people. Giving metformin to aged mice or rats rejuvenates their oligodendrocyte progenitor cells so that they respond better to remyelinating drugs like clemastine.
PILOT HEALTHY BRAIN AGEING CLINIC
Outside of a research context, many opportunities already exist to improve brain health by targeting biological ageing. These include boosting physical activity, supporting other healthy behaviours and optimising the management of any co-existing medical conditions.
With involvement from patient and public contributors (including our Public Collaborators Ageing in MS focus group) we are launching a pilot Healthy Brain Ageing Clinic, funded by the NIHR Cambridge Biomedical Research Centre.
Participants will have a comprehensive review of their health and lifestyle, learn about their biological age, and work with a multi-disciplinary professional team to develop personalised strategies to improve long-term brain health.
Meet the Group
Learn a little more about each member of the Ageing and Brain Health group by clicking on their profile picture below.
Dr Chris McMurran
Group Lead
Prof Alasdair Coles
Head of Group
Dr Jonathon Holland
Ph.D. Candidate
Dr Trisha Mukherjee
Ph.D. Candidate
Lucas Paulo de Lima Camillo
Medical Student
Dorsa Manavi
Medical Student
Publications
Publications
Brain
Volume 149, Issue 1, January 2026
Ageing and remyelination failure in people with multiple sclerosis
Remyelination is a promising strategy for preventing or reversing disability progression in multiple sclerosis, but preclinical research suggests that its effectiveness may decline with age. This review examines the available evidence on the relationship between ageing and remyelination in people with multiple sclerosis, bringing together pathological, imaging and clinical studies. Overall, the evidence suggests that the capacity for endogenous remyelination decreases with advancing age, although findings are not consistent and the precise contribution of ageing remains unclear. Importantly, remyelination appears to remain possible across the lifespan, with some evidence suggesting that its effectiveness may vary according to lesion location, while lesion age and disease duration are important factors that can confound the relationship between age and remyelination. These findings highlight the need for further research to better understand how chronological and biological ageing influence remyelination and whether this age-related decline can be therapeutically reversed. A clearer understanding of this relationship could help identify people most likely to benefit from remyelinating therapies and inform the optimal timing of treatment.
Publications
Trials
Volume 26, Article 562, December 2025
The Cambridge Centre for Myelin Repair trial Two (CCMR Two): a trial protocol for a phase 2a, randomised, double-blind, placebo-controlled clinical trial of the ability of the combination of metformin and clemastine to promote remyelination in people with relapsing-remitting multiple sclerosis already on disease-modifying therapy
The Cambridge Centre for Myelin Repair Two (CCMR-Two) trial was designed to evaluate whether the combination of metformin and clemastine can enhance remyelination in people with relapsing-remitting multiple sclerosis. Building on preclinical evidence that metformin restores the responsiveness of ageing oligodendrocyte progenitor cells to pro-remyelinating signals, this study combines metformin with clemastine, a drug previously shown to promote oligodendrocyte differentiation. In this randomised, placebo-controlled trial, 70 participants with chronic stable optic neuropathy received either active treatment or placebo for 24 weeks. The primary endpoint was change in visual evoked potential (VEP) P100 latency, a sensitive measure of myelin repair, with secondary outcomes including multifocal VEP and lesion magnetisation transfer ratio (MTR). The study was designed to detect both functional and structural evidence of remyelination within a feasible single-centre clinical trial framework. This article outlines the full protocol used for the trial.
Publications
Aging Cell
Volume 24, Issue 8, August 2025
Brain DNA Methylation Age, Lifestyle Factors and Dementia in the Swedish Twin Registry
Advanced age is the strongest risk factor for dementia, but measures of biological ageing may provide additional insight into the processes underlying age-related brain changes. Although dementia is a very different condition from multiple sclerosis (MS), both involve loss of nerve cells and are closely tied to brain ageing, and we can learn from studying overlapping mechanisms. Using post-mortem brain tissue and paired blood samples from participants in the Swedish Twin Registry, this study investigated the relationship between biological ageing in the brain, lifestyle factors and dementia. Smoking was associated with accelerated biological ageing in the prefrontal cortex, with greater smoking exposure linked to older biological age, while a longer time spent in formal education was associated with younger biological age. In contrast, there was no significant difference in measures of biological ageing between people with dementia and controls, although there was a trend towards older biological age in the prefrontal cortex among those with more advanced tau pathology. Furthermore, measures of biological ageing in the brain and blood were not clearly associated, suggesting that ageing may occur differently across tissues. Together, these findings suggest that modifiable lifestyle factors may influence biological ageing in the brain and highlight the potential value of brain-specific measures when investigating the risk and development of dementia.
Publications
Brain
Volume 146, Issue 12, December 2023
Advanced biological ageing predicts future risk for neurological diagnoses and clinical examination findings
People age at different rates, and measures of biological ageing may help explain why some individuals develop neurological disease earlier than others despite having the same chronological age. Although stroke and dementia are very different conditions from multiple sclerosis (MS), both involve loss of nerve cells and are closely tied to brain ageing, and we can learn from studying overlapping mechanisms. Using data from 802 participants in the Swedish Adoption/Twin Study of Aging (SATSA), followed over several decades, this study investigated whether accelerated biological ageing was associated with future neurological disease and abnormalities on clinical examination. Six measures of biological age were assessed using physiological and blood biomarkers and DNA methylation. Older physiological ages were associated with an increased risk of future ischaemic stroke, with each standard deviation increase in biological age associated with a 29.2% to 42.9% greater risk, while older methylation age was associated with a 29.7% greater risk of dementia per standard deviation increase. Older physiological age was also associated with the future development of abnormal reflexes and gait. Together, these findings demonstrate that biological ageing can predict clinically relevant neurological pathology independently of chronological age and may help explain differences in neurological disease risk between individuals of the same age. They also support further investigation of interventions that target the biology of ageing as a potential strategy for preventing or delaying age-associated neurological disease.
Click on the paper titles below to view the key publications to which members of the Ageing and Brain Health group have contributed.
Ageing and remyelination failure in people with multiple sclerosis, Brain (2026)
Brain DNA Methylation Age, Lifestyle Factors and Dementia in the Swedish Twin Registry, Aging Cell (2025)
Exploratory analysis of biological age measures in a remyelination clinical trial, Brain Communications (2025)
Regulatory T cells limit age-associated retinal inflammation and neurodegeneration, Molecular Neurodegeneration (2024)
Ageing impairs the regenerative capacity of regulatory T cells in mouse central nervous system remyelination, Nature Communications (2024)
Visual outcome measures in clinical trials of remyelinating drugs, BMJ Neurology Open (2024)
Changes in the Oligodendrocyte Progenitor Cell Proteome with Ageing, Molecular & Cellular Proteomics (2020)
CNS Remyelination and the Innate Immune System, Frontiers in Cell and Developmental Biology (2016)