Older adults who lose muscle mass and gain body fat through a condition called sarcopenic obesity could risk developing chronic, age-related conditions such as Alzheimer's disease. Brock University PhD student Emily Copeland (BSc '20, MSc '22) is determined to understand why.
PhD student Emily Copeland is lead author on a recent review examining how levels of a protein a protein called brain derived neurotrophic factor impacts muscle, body weight and brain health.
Copeland is the lead author on a recently published research review exploring the impacts of a protein called brain derived neurotrophic factor (BDNF) on brain functioning, skeletal muscles and body fat.
BDNF plays an important role in neuron development and other brain processes and is essential for learning and memory. The vital protein is lower in people living with Alzheimer's and particularly in post-menopausal women.
"Knowing that BDNF declines with age and plays a role in both muscle and brain, we thought that it might be an important factor for healthy aging," Copeland says. "Sarcopenic obesity and Alzheimer's disease are two common age-related diseases, so we wanted to see how BDNF might be affected by them."
The team which also included co-leads Associate Professors of Kinesiology Val Fajardo and Health Sciences Rebecca MacPherson, who serve as Copeland's supervisors, as well as Professor of Health Sciences Paul LeBlanc and Assistant Professor of Psychology Paula Duarte-Guterman reviewed almost 100 scientific studies.
Copeland says the review shows how muscle wasting and weight gain associated with sarcopenic obesity contributes to Alzheimer's disease, and the role BDNF could play in treating these conditions.
"If you have more BDNF, you're more protected from developing Alzheimer's," she says. "You'll have better skeletal muscle health, and BDNF is linked to lower obesity as well."
Targeting BDNF-related pathways can inform both pharmacological and lifestyle interventions, including exercise, adds MacPherson.
"Exercise is one of the most robust physiological stimuli for increasing BDNF," she says. "The best part is that exercise is a simple strategy to boost brain health that is accessible to almost everyone."
The review found that, in studies on animal models, higher levels of BDNF decreased overactivity of an enzyme called GSK3, leading to fewer beta amyloid and neurofibrillary tangles, which are evidence of Alzheimer's disease in the brain. These plaques and tangles increased in both animal and human tissues with lower levels of BDNF.
BDNF was also shown to repair muscle, burn fat and boost the performance of mitochondria a sub-unit within a cell that regulates muscle endurance, insulin sensitivity and protein generation in studies using animal models.
When muscles fibres are injured or break down because they aren't being used, skeletal muscle repair and regeneration take place by a type of stem cell called satellite cells. These mechanisms decline as the body ages.
For older adults grappling with sarcopenic obesity, this muscle repair doesn't function well. According to the team's review, research links this impairment to decreased BDNF levels.
With muscle wasting and insulin insensitivity, more body fat called adipose tissue is created, especially in the abdomen, leading to obesity, chronic low-grade inflammation and problems with metabolism.
"Alzheimer's has become known as Type 3 diabetes," says Copeland. "Inflammation created with this type of insulin resistance in adipose tissue throughout the body crosses over into the brain. When the brain becomes resistant to insulin, it can increase amyloid beta production and overload the brains inflammatory response, putting the brain at higher risk for Alzheimer's disease."
Animal model studies reviewed by the team showed BDNF injections reduced body weight and the amount of adipose tissue that, in turn, reduced inflammation and improves insulin sensitivity.
The team's insights can be found in their review paper, "The link between sarcopenic obesity and Alzheimer's disease: a brain-derived neurotrophic factor point of view," published last month in the Journal of Physiology.
Supporting the team's research is funding from the Government of Canada's Natural Sciences and Engineering Research Council of Canada and the Canadian Institutes of Health Research.
