Research
Groundbreaking study reveals substance use accelerates brain ageing through distinct molecular pathways

Researchers have uncovered crucial evidence that substance use disorders (SUDs) accelerate biological ageing in the brain through distinct molecular mechanisms. The groundbreaking study examines how different substances, such as alcohol, opioids, and stimulants, affect the brain’s ageing process at the molecular level, potentially explaining why individuals with SUDs often experience early-onset age-related diseases.
The research team, analysed brain tissue from 58 donors with SUDs to assess differential ageing patterns using specialised epigenetic clocks designed specifically for brain tissues.
Unlike previous studies that relied on more general epigenetic ageing markers, this investigation employed brain-specific tools (DNAmClockCortical, CerebralCortexClockcommon, and PCBrainAge) to provide a more accurate assessment of neural ageing.
“Our study is the first to investigate brain accelerated ageing in substance use disorders using epigenetic clocks specifically designed for brain tissues,” explains Dr. Kluwe-Schiavon.
“This approach allowed us to capture unique aspects of the ageing process in the brain that might have been missed with more general methods.”
The researchers, led by Drs. Bruno Kluwe-Schiavon, Gabriel Fries, and Consuelo Walss-Bass, focused on the dorsolateral prefrontal cortex, a brain region central to decision-making and executive control that is particularly vulnerable to addiction. By examining postmortem brain tissue and conducting sophisticated gene expression analyses, the team identified specific molecular signatures associated with accelerated ageing in different SUDs.
One of the study’s most significant findings was that different substances appear to accelerate brain ageing through distinct biological pathways. In alcohol use disorder, researchers found altered expression of genes involved in protein phosphorylation, signal transduction, and glutamatergic synapse function. For opioid use disorder, transcriptional regulation, neurodevelopment, and immune-inflammatory processes emerged as key drivers of accelerated ageing.
Stimulant use disorder showed distinct patterns related to oxidative stress, hypoxia responses, and cell adhesion pathways.
Dr. Walss-Bass said: “We’ve discovered that accelerated ageing in substance use disorders is not a uniform process. Each substance appears to hijack the brain’s natural ageing rhythm through unique molecular mechanisms, though some pathways are shared across different substance types.”
Despite the differences between substances, the research identified some common biological mechanisms across all SUDs. Neuroinflammation, oxidative stress, and mitochondrial dysfunction appeared to play crucial roles in accelerated ageing regardless of the specific substance used.
“Our integrative analysis suggests that mitochondrial function, the powerhouse of the cell, is central to maintaining cellular energy homeostasis and regulating oxidative stress responses,” notes Dr. Gabriel Fries, co-corresponding author of the study.
“When substance use disrupts these processes, it can accelerate the biological ageing of neural tissue.”
The findings have profound implications for public health, addiction medicine, and treatment approaches. If substance use induces premature biological ageing, it should be viewed not merely as a behavioural choice but as an accelerant of neurodegeneration.
“What we call relapse may sometimes be the cognitive exhaustion of a prematurely aged cortex,” said Dr. Kluwe-Schiavon.
“This perspective shifts how we think about addiction treatment and recovery.”
The research opens the door to a new field that the authors describe as “the psychiatry of ageing in young people.” It calls for longitudinal investigations that follow individuals through abstinence, relapse, remission, and decay, as well as integrative biomarker panels that combine methylation, gene expression, and neuroimaging.
In his accompanying editorial, Dr. Julio Licinio offers a thought-provoking perspective on the study’s implications.
“This is not just a question of whether drugs kill. We already know they do. The deeper question, provocative and new, thanks to this anatomically grounded work, is whether drugs age the brain,” writes Dr. Licinio.
He emphasises that the ageing effects observed in substance use disorders are “neither cosmetic nor metaphorical. It is cellular. It is molecular. And it is coded into the methylated terrain of the genome.”
Dr. Licinio notes that the findings have implications far beyond the laboratory, reaching into public health, addiction medicine, criminal justice, and education policy.
“If substance use induces premature biological ageing, then we must treat it not merely as a moral lapse or behavioural choice, but as an accelerant of neurodegeneration,” he argues.
While the study provides valuable insights, the researchers acknowledge several limitations, including the relatively small sample size and cross-sectional design, which limits causal interpretations. They call for future research with larger cohorts and longitudinal designs to confirm their findings and further elucidate the mechanisms of accelerated ageing in different SUDs.
An intriguing question emerging from this research is why some brains deteriorate faster than others under similar pharmacological conditions. Could there be predisposing genomic signatures, either genetic susceptibilities or epigenetic scars left by early-life adversity, that make some individuals biologically more vulnerable to substance-induced ageing?
“If one is to be optimistic, and one must be, even in the face of molecular entropy, then perhaps these findings mark the beginning of a therapeutic redirection,” Dr. Licinio suggests in his editorial.
“Anti-ageing interventions, long the obsession of cosmetic medicine and Silicon Valley biohackers, might soon find their most ethically urgent application in addiction psychiatry.”
News
NHS to review cost effectiveness of new Alzheimer’s drugs

NICE will review whether new Alzheimer’s drugs should be offered on the NHS after an appeal found their wider impact was not fully counted.
An appeal found that the National Institute for Health and Care Excellence had failed to properly account for the wider impact of the treatments, including the heavy burden on unpaid carers, when calculating the cost effectiveness of the medicines.
Both treatments, lecanemab and donanemab, will now return to a NICE committee for further consideration.
“Today’s ruling is an opportunity for NICE to consider the real cost of Alzheimer’s on people and their families, and we welcome the decision to look again at whether new medicines could be provided on the NHS,” said David Thomas, head of policy and public affairs at Alzheimer’s Research UK.
Lecanemab and donanemab do not cure Alzheimer’s, but they slow it by targeting and clearing clumps of amyloid proteins, sticky protein build-ups in the brain linked to the disease.
While the drugs are available privately in the UK for people who can afford them, NICE ruled last year that they were too expensive to be made available on the NHS in England and Wales.
It is estimated informal dementia care costs the economy more than £20bn a year.
Alzheimer’s Research UK wants NICE to update how it assesses the value of new dementia drugs and factor in the huge additional costs this condition places on society and the wider economy.
NICE and its expert committees assess whether new drugs are good value for money for the NHS based on a wide range of evidence.
This includes how treatments perform in clinical trials, the experiences of patients and carers, and the costs of new drugs as well as any changes to NHS services needed to provide access.
When NICE weighs up whether a new Alzheimer’s drug is cost effective for the NHS, it carries out a limited assessment of the impact dementia has on the health of carers.
But the condition takes an enormous toll on families and society because caring for someone with dementia can lead people to become more isolated and give up work.
It can have a major emotional impact and put families under financial strain.
Thomas said: “Research has delivered new treatments with the potential to provide people with valuable extra months of independence, lessening the burden on carers.
“While these treatments offer modest benefits and can cause serious side effects, they provide the foundation for a future where dementia becomes a treatable condition.
“Now we need NICE to look again at how these medicines could benefit both people with early Alzheimer’s and their carers.”
Chris, whose mother Shirley is living with Alzheimer’s disease, said: “The real cost of Alzheimer’s is far greater than many people realise.
“In order to give my mum the care she needed, I moved back home to help my dad as the care was too much for him alone. After my dad passed away from Covid in 2021, I became sole carer for my mum.
“It was a very difficult period, working a full-time job, caring for Mum and dealing with the loss of my dad. Eventually I got some in-home care support to help.
“The family has borne most of the cost of Mum’s care, both in time and fees, and the family home has been sold to finance it.”
“The emotional and financial strain Alzheimer’s has taken on our family is horrendous, and I know many families across the UK are experiencing this pressure.”
He is backing Alzheimer’s Research UK’s call for NICE to change how it evaluates new dementia treatments.
The timeframe for the next NICE meetings to discuss the drugs is still to be set, and it is not certain follow-up hearings would change NICE’s guidance on access to the medicines.
But Alzheimer’s Research UK is continuing to push to make sure dementia is now a main priority for political and NHS decision-makers.
The head of the ongoing independent review into adult social care, Baroness Louise Casey, has called on the government to act, show leadership and prioritise dementia.
She has proposed appointing a dementia tsar to drive forward the prevention, treatment and care of dementia.
Baroness Casey has also argued for more funding for dementia treatment trials.
With more than 130 Alzheimer’s drugs in clinical trials worldwide, the charity says it is vital the NHS runs trials of new treatments now to understand how to deliver them to eligible patients in future.
In addition to changing how NICE assesses new medicines, the health service needs to collect real-world evidence on new dementia drugs and prepare for diagnostic tests and innovative treatments that are coming.
“Alzheimer’s Research UK is calling on the government to give dementia the same political determination that transformed cancer care,” Thomas said.
“We urgently need investment and a clear UK-wide plan so new treatments can be assessed in the NHS and reach the people who stand to benefit.”
Health and social care secretary Wes Streeting has said dementia is “one of the greatest challenges of our time” and pledged that the UK should become a world leader in dementia clinical trials.
News
Osteoporosis drugs could reduce dementia risk, study suggests
News
Gut health supplement relieves arthritis pain, research finds

A prebiotic fibre supplement may ease arthritis pain and improve grip strength in people with knee osteoarthritis, a study suggests.
The daily supplement, made from inulin, a dietary fibre found in chicory root, Jerusalem artichokes and other vegetables, also lowered pain sensitivity and saw fewer people drop out than a digital physiotherapy programme tested alongside it.
Dr Afroditi Kouraki, lead author of the study from the University of Nottingham, said: ‘Our findings suggest that targeting gut health with a prebiotic supplement is a safe, well-tolerated, and effective way to reduce pain in people with knee osteoarthritis.
“The very low dropout rate compared to the exercise group is also encouraging from a public health perspective, people were able to fit this supplement easily into their daily lives.’
Osteoarthritis of the knee, a wear-and-tear joint condition, affects hundreds of millions of people worldwide and is a leading cause of pain and disability, particularly in older adults.
Current treatments rely heavily on pain medication, which can cause side effects, or exercise programmes, which many patients find hard to maintain.
The INSPIRE trial, led by researchers at the University of Nottingham, involved 117 adults with knee osteoarthritis and tested four groups: inulin alone, digital physiotherapy-supported exercise alone, a combination of both, and a placebo. Both inulin and physiotherapy independently reduced knee pain.
However, inulin alone improved grip strength and reduced pain sensitivity, measures linked to how the nervous system processes pain, while physiotherapy did not.
The dropout rate for those taking the supplement was just 3.6 per cent, compared with 21 per cent for the physiotherapy group, suggesting a daily supplement may be easier for people to stick with than an exercise programme.
Inulin works as a prebiotic, meaning it feeds beneficial bacteria in the gut.
This leads to the production of compounds called short-chain fatty acids, particularly butyrate, which can affect inflammation and pain pathways throughout the body.
Participants taking inulin also showed increased levels of both butyrate and GLP-1, a gut hormone linked to pain regulation and muscle health.
Higher GLP-1 levels were associated with improved grip strength, pointing to a possible gut-muscle connection.
Senior author Professor Ana Valdes added: ‘The link we observed between GLP-1 and grip strength is particularly intriguing and points to a broader gut-muscle-pain axis that warrants further investigation. This could have implications not just for osteoarthritis, but for understanding how gut health influences ageing and physical resilience more broadly.’
Professor Lucy Donaldson, director of research at Arthritis UK, said: “The pain of arthritis can severely impact quality of life. Our recent lived experience survey showed that six in ten people are living in pain most or all of the time due to their arthritis.
“Researchers are starting to explore the role of the gut microbiome in our experience of pain.
“This exciting preliminary research highlights how diet and physiotherapy can act in different ways to have benefits for people with arthritis.
“We know a variety and balance of healthy foods, including fibre, and regular physical activity matter, and we’re glad to be supporting research that explores how they work to help people with arthritis.”
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