Precision Exercise Medicine: Sex Specific Differences in Immune and CNS Responses to Physical Activity

Abstract

Physical activity is a powerful lifestyle factor capable of improving cognitive function, modifying the risk for dementia associated with neurodegeneration and possibly slowing neurodegenerative disease progression in both men and women. However, men and women show differences in the biological responses to physical activity and in the vulnerabilities to the onset, progression and outcome of neurodegenerative diseases, prompting the question of whether sex-specific regulatory mechanisms might differentially modulate the benefits of exercise on the brain. Mechanistic studies aimed to better understand how physical activity improves brain health and function suggest that the brain responds to physical exercise by overall reducing neuroinflammation and increasing neuroplasticity. Here, we review the emerging literature considering sex-specific differences in the immune system response to exercise as a potential mechanism by which physical activity affects the brain. Although the literature addressing sex differences in this light is limited, the initial findings suggest a potential influence of biological sex in the brain benefits of exercise, and lay out a scientific foundation to support very much needed studies investigating the potential effects of sex-differences on exercise neurobiology. Considering biological sex and sex-differences in the neurobiological hallmarks of exercise will help to enhance our understanding of the mechanisms by which physical activity benefits the brain and also improve the development of treatments and interventions for diseases of the central nervous system.

Skeletal muscle TFEB signaling promotes central nervous system function and reduces neuroinflammation during aging and neurodegenerative disease

“… 59 While it is unclear whether these differential responses between male and female hippocampi reflect local differences in the CNS itself 60 or peripheral differences in the expression, secretion, or trafficking of circulating signals, they underscore the fundamental need to examine sex differences contributing to the biology of aging and neurodegenerative diseases. 61 …”

Prevention of Vascular Contributions to Cognitive Impairment and Dementia: The Role of Physical Activity and Exercise

“…98 Preliminary evidence also suggests sex differences in myokine secretion, but more studies designed specifically to compare the sexes are needed. 6,99 Moreover, the majority of research has focused on AT-induced myokines, but it is crucial to shift focus to RT-induced myokines, given the clinical relevance of muscle mass and strength. 100 Older adults with sarcopenia are at an increased risk of cardiometabolic diseases, arterial stiffness, ischemic brain injury, including WMHs.…”

Skeletal Muscle TFEB Signaling Promotes Central Nervous System Function and Reduces Neuroinflammation during Aging and Neurodegenerative Disease

“…mitochondrial function) mice 66 . While it is unclear whether these differential responses between male and female hippocampi reflect local differences in the CNS itself (as recently published here 67 ) or peripheral differences in the expression, secretion or trafficking of circulating signals (such as Ctsb, for example), they underscore the fundamental need to examine sex differences contributing to the biology of aging and neurodegenerative diseases 68 .…”