Randomized trial shows exercise reduces brain age by 0.6 years in adults — Evidence Review

A new randomized controlled trial from the AdventHealth Research Institute finds that maintaining a year-long aerobic exercise routine can help keep the brain biologically younger in healthy adults. These results align with a broad body of research linking regular physical activity to improved brain structure, cognitive function, and reduced age-related brain changes.

• Multiple studies show that aerobic exercise and higher physical activity levels are linked to greater brain volume, improved white matter integrity, and better cognitive function in older adults, reinforcing the new study’s findings of exercise-induced reductions in brain-predicted age difference (brain-PAD) 1 2 6 7.
• The modest reduction in brain age observed in the new trial is consistent with meta-analyses and systematic reviews showing small but significant benefits of exercise on brain structure and cognition, both in healthy individuals and those at risk for decline 4 6 9.
• While mechanisms remain under investigation, related studies suggest benefits may arise from improved neuroplasticity, growth factor cascades, and vascular health, although the precise pathways—such as those affecting brain-PAD—are still being explored 11 13 15.

Study Overview and Key Findings

Research on how to protect brain health across the lifespan has often focused on older adults, leaving a gap in understanding how midlife interventions might prevent or slow age-related brain changes before cognitive decline emerges. This new study addresses that gap by targeting adults aged 26 to 58, using MRI-based measures of brain age to assess whether a year-long aerobic exercise regimen can measurably impact biological brain aging. The study’s focus on brain-predicted age difference (brain-PAD) provides a direct, objective marker of brain health, moving beyond traditional cognitive or fitness outcomes.

Property	Value
Organization	AdventHealth Research Institute, University of Pittsburgh
Journal Name	Journal of Sport and Health Science
Authors	Dr. Lu Wan, Dr. Kirk I. Erickson
Population	Healthy adults aged 26 to 58
Sample Size	n=130
Methods	Randomized Controlled Trial (RCT)
Outcome	Brain age, cardiorespiratory fitness
Results	Exercise group saw brain-PAD drop by about 0.6 years

Literature Review: Related Studies

To place these findings in context, we searched the Consensus database, which aggregates over 200 million research papers. We used the following search queries to identify relevant studies:

1. exercise brain age MRI scans
2. physical activity cognitive function aging
3. brain health effects of exercise

The following table summarizes key topics and findings from the related literature:

Topic	Key Findings
How does aerobic exercise impact brain structure and age-related brain changes?	- Aerobic exercise training increases brain volume and helps preserve both gray and white matter in older adults, with positive effects observed via MRI 1 2. - Exercise moderates age-related atrophy, particularly in the medial temporal lobe, and improves white matter structure 2 3.
What are the cognitive effects of physical activity and exercise across age groups and health states?	- Exercise interventions improve cognitive function in adults over 50, regardless of cognitive status, with benefits seen in memory, executive function, and processing speed 6 7 9 10. - Physical activity also benefits cognition and mood in brain disorders like Alzheimer's disease 8 14.
What mechanisms link physical activity to brain health and aging?	- Exercise-induced benefits may be mediated by increased neuroplasticity, growth factor cascades (e.g., BDNF), improved vascular health, and reduced inflammation 11 13 15. - The precise biological pathways remain incompletely understood, with multiple mechanisms likely involved 11 15.
Are there dose-response or modality-specific effects of exercise on brain health?	- Multicomponent approaches (aerobic plus resistance training) may offer the greatest cognitive benefits, but aerobic exercise alone is consistently effective 6 10. - The magnitude of brain and cognitive effects tends to be small to moderate, with longer interventions showing greater impact 5 6 10.

How does aerobic exercise impact brain structure and age-related brain changes?

The literature consistently demonstrates that aerobic exercise can induce structural brain changes, including increased gray and white matter volumes and reduced atrophy in regions vulnerable to aging. Several trials using MRI have documented that regular aerobic activity helps maintain or increase brain tissue, especially in older adults, which aligns with the new study’s finding that exercise can decrease brain-PAD, a biomarker of brain age 1 2 3.

• Aerobic training has been shown to increase overall brain volume and protect against age-related tissue loss in both gray and white matter 1.
• Higher physical activity and fitness levels are linked to better white matter integrity and reduced severity of white matter lesions, though effect sizes are generally small 2.
• Exercise may selectively preserve regions such as the medial temporal lobe, which is important for memory and highly susceptible to age-related decline 3.
• The new study’s use of brain-PAD as an outcome is a novel approach that builds on these volumetric findings with a global marker of brain aging 1 2 3.

What are the cognitive effects of physical activity and exercise across age groups and health states?

Meta-analyses and systematic reviews reveal that physical exercise—particularly aerobic activity—improves cognitive function in adults over 50, regardless of baseline cognitive status. These benefits extend to multiple cognitive domains and are also reported in individuals with various brain disorders. The new study’s focus on younger and midlife adults expands this evidence base by suggesting that exercise may help maintain brain health before overt cognitive decline occurs 6 7 8 9 10 14.

• Physical exercise interventions improve memory, executive function, and processing speed in older adults, with small but statistically significant effects 6 7 9 10.
• Benefits are observed for both healthy individuals and those with cognitive impairment or chronic brain disorders 8 14.
• Multicomponent training may be particularly effective, but aerobic exercise alone also provides clear benefits 6 10.
• The present study supports the idea that even modest shifts in biological brain age could translate into meaningful cognitive differences over time 6 7 10.

What mechanisms link physical activity to brain health and aging?

While improvements in fitness and reductions in cardiovascular risk factors are often cited as mediators of exercise’s benefits, recent research points to additional mechanisms at the molecular and structural levels. Exercise-induced increases in neurotrophic factors like BDNF, enhanced neuroplasticity, improved vascular function, and reductions in inflammation are all implicated. The new study’s finding that the reduction in brain-PAD was not explained by changes in fitness, blood pressure, or BDNF highlights the complexity and likely multifactorial nature of these processes 11 13 15.

• Exercise triggers growth factor cascades (e.g., BDNF) that promote synaptic plasticity, neurogenesis, and vascular health, supporting learning and memory 11 13.
• Muscle-brain endocrine signaling, involving myokines and other factors, plays a role in mediating the effects of exercise on the brain 13.
• Reduced inflammation may be a common pathway linking peripheral and central exercise benefits 11 13 15.
• The precise biological mechanisms remain incompletely understood, with variation likely based on age, health status, and exercise modality 11 15.

Are there dose-response or modality-specific effects of exercise on brain health?

Evidence suggests that both the type and duration of exercise influence brain and cognitive outcomes. Multicomponent interventions (aerobic plus resistance) may offer greater cognitive benefits, but aerobic exercise alone is consistently effective. Longer and more intense interventions tend to yield greater improvements, although the effect sizes remain small to moderate 5 6 10.

• Meta-analyses report that 45–60 minutes of moderate-intensity exercise per session, multiple times per week, is associated with the largest cognitive gains 6 10.
• The impact of exercise on brain structure and function appears to be more pronounced with longer intervention durations 5.
• While all exercise modalities offer some benefit, combining aerobic and resistance training may maximize cognitive improvements 6 10.
• The new study’s protocol of 150 minutes per week of moderate-to-vigorous aerobic activity aligns with current guidelines and reinforces the importance of sustained, guideline-based exercise 6 10.

Future Research Questions

While the current study advances understanding of how aerobic exercise influences biological brain aging in midlife, several areas require further investigation to clarify long-term impacts, underlying mechanisms, and practical applications.

Research Question	Relevance
Do reductions in brain-predicted age difference (brain-PAD) from exercise persist over multiple years?	It is unclear whether the observed decrease in brain-PAD is maintained with continued exercise or if the effects diminish over time. Longitudinal studies are needed to assess the durability of brain age changes and their clinical relevance 2 5 6.
Which molecular and structural mechanisms mediate the impact of exercise on brain aging?	The modest brain-PAD reduction was not explained by changes in fitness, BDNF, or blood pressure, suggesting other mechanisms are involved. Identifying these pathways may help optimize interventions and clarify how exercise protects brain health 11 13 15.
How do different types and intensities of exercise affect brain age and cognition across the lifespan?	There is ongoing debate about the relative benefits of aerobic, resistance, and multicomponent training, as well as the optimal dose for brain health at different ages. Comparative studies can inform exercise guidelines for cognitive and brain outcomes 6 10.
Does lowering brain age through exercise reduce the risk of dementia and other neurological diseases later in life?	The clinical significance of lowering brain-PAD remains uncertain: whether these changes translate into reduced incidence of cognitive impairment, stroke, or dementia requires larger, long-term studies with diverse populations 7 8 14.
Are the effects of exercise on brain aging consistent across different demographic and risk groups?	Most trials, including the current one, focus on healthy, well-educated adults. Research is needed to determine if similar benefits occur in more diverse or at-risk populations, such as those with metabolic disorders or genetic risk factors 6 8 14.