A new clinical trial, led by researchers at the Institute of Psychiatry, Psychology & Neuroscience, has found that exercise has a significant effect on mood and lab-based measures of new brain cell formation in healthy middle-aged participants.
The Neurofit study investigated the effect of a 3-month exercise intervention programme on cognitive performance, mood, and biological indicators of new neuron production in middle age. Previous studies have found middle age to be a period of increased psychological distress and changes in cognition. This period can come at the same time as a reduction in physical activity, due to changes in work or social patterns.
Existing studies in animal models have also shown positive effects of exercise on cognitive performance. These benefits are accompanied by more neurons being made from stem cells in the hippocampus, a key part of the brain involved in memory and cognition. The Neurofit clinical trial aimed to evaluate the effect of exercise on these same factors in humans.
Measuring cognitive function
There are many possible ways to measure cognitive function. In this study, the researchers looked at how 3 months of exercise impacted performance in a type of cognitive task called pattern separation. The researchers chose one particular task, called the Mnemonic Similarity Task, which tests participants' ability to differentiate sets of similar items. This task is particularly dependent on the hippocampus, a key part of the brain that is affected by age-related changes and Alzheimer's disease.
The results of the randomised controlled trial, involving 52 healthy participants between the ages of 45 and 65, were published in npj Aging. Of the 52 participants, 27 performed a combination of aerobic and resistance training three times a week for three months, while the other 25 were assigned to a control group that did not. While no effect of exercise was found on cognitive performance (the primary outcome) at three months, participants who partook in the exercise programme had a significant increase in mood related measures compared to those in the control group. Changes were also seen in laboratory tests that act as a proxy for the brain's ability to make new hippocampal neurons.
"Our findings suggest that just three months of exercise may be sufficient to significantly improve mood, even in healthy individuals without depressive symptoms, while cognitive benefits, particularly those involving hippocampal function, may require either a longer period of exercise or a more intensive exercise programme to emerge," commented Sahand Farmand, PhD student and first author on the study.
Making new neurons as an adult
Few parts of the adult human brain are able to make new neurons. Most of the cells in our brain are given their roles during development, some will be neurons, some will be support cells called glia. There are different types of neurons, all with specialised functions and normally once cell has specialised, it will not change its type. The hippocampus is one of the only parts of the adult brain that keeps a reserve of unspecialised stem cells ready to transition into neurons later in life.
Looking at new neuron formation in humans
Directly measuring how many stem cells are turning into new hippocampal neurons in humans would be highly invasive and neither feasible nor ethical for a clinical trial. Instead, researchers look at stem cells in the lab by adding a distilled blood sample (called serum) to see if the factors in the participant's blood cause more stem cells to turn into neurons. They can then compare whether serum from people who had the intervention (for example, a 3-month exercise programme) behaves differently to serum from people who didn't.
To assess how exercise may impact brain health, the researchers took samples of blood serum from the exercise group and added them to human hippocampal stem cells in the lab. This procedure provides as a non-invasive proxy for measuring how exercise affects the development of new neurons in the hippocampus from stem cells.
Adding blood serum from the exercise group caused fewer hippocampal stem cells to be in a proliferation state compared to blood serum from the control group. The researchers suggest this may be due to stem cells being held in a state where they are reserved for future specialised use.
"We were initially surprised that blood serum from people who followed the exercise programme reduced the number of stem cells available to develop into new neurons," commented Professor Sandrine Thuret, Professor of Neuroscience at King's College London.
"However, as the brain has a finite pool of stem cells, we think the brain may be reserving some of them for later use, rather than using them all at once. Exercise might be helping this process."
The researchers observed that for some individuals, exercise had strong effects on both cognitive performance, mood and lab tests. Future work will investigate the molecular mechanisms driving this response.
These results form part of a larger study, joint with APC Microbiome Ireland at University College Cork, that is also investigating the effect of exercise on gut microbiota and the gut-brain axis.
This work was primarily funded by the Reta Lila Weston Trust. Additional funding came from the UKRI Ageing Across the Lifecourse Networks Biotechnology and Biological Sciences Research Council (BBSRC),
Effects of a three-month exercise programme on cognition, mood and neurogenesis: The NeuroFit randomised controlled trial (DOI: 10.1038/s41514-026-00439-w, Farmand et al.) was published in npj Aging.
