The doctoral dissertation in the field of Molecular Medicine will be examined at the Faculty of Health Sciences.
What is the topic of your doctoral research? Why is it important to study the topic?
Healthy aging is an important mission not only for decreasing the risk of disease development, but also for the maintenance of the functional ability of people throughout their whole lifespan. With the increasing elderly population, age-related disorders including Alzheimer’s disease (AD) have become a major public health problem. AD is the first leading cause of dementia with no effective treatment nowadays. This is most likely due to our still limited understanding of the disease mechanisms. Even though aging and genetic predisposition are the major AD risk factors, there are also lifestyle factors such as physical inactivity which exert a huge impact on the development of AD.
The primary goal of this thesis was to provide new understandings on the beneficial mechanisms induced by regular physical exercise both in the brain and periphery, in the context of aging and AD. Understanding the cellular and molecular events associated with lifestyle modulation such as regular exercise will be highly important for limiting age- and AD-related pathology via non-pharmacological strategy and promoting healthy aging.
What are the key findings or observations of your doctoral research?
According to our results, long-term voluntary exercise was protective against age-related cellular stress in skeletal muscle of mice upon aging. The beneficial exercise effect is linked with improved redox regulation, endoplasmic reticulum (ER) stress adaptation and heat shock protein (HSP) defense. Further, long-term voluntary exercise was beneficial against cognitive impairment developing in the 5xFAD mouse model of AD and was associated with remodelling of glial cells – astrocytes. Exercise-induced beneficial effect in AD was associated with increased number and altered morphology of GFAP-positive astrocytes, which could be linked with the restoration of astrocytic brain derived neurotrophic factor (BNDF). Moreover, long-term voluntary exercise modulates brain and peripheral iron metabolism, which is altered in AD. This study is the first which links brain iron status with the reduction of iron regulator protein hepcidin in mice undergoing exercise. The results suggest that regular exercise regulates iron homeostasis decreasing hepcidin levels in the brain possibly via an attenuation of the interleukin-6 (IL-6)/STAT3 pathway.
These findings reveal new aspects of the beneficial effect of long-term physical exercise in both the brain and skeletal muscle and collectively highlight the positive impact of regular exercise on aging and AD.
Please describe the process of your doctoral research.
The effects of long-term physical exercise in aging and AD were studied by using mouse models. To study effect of long-term voluntary exercise on aging, 3-months-old ICR mice were used and mice from the voluntary exercise group had unlimited use of a running wheel for 21 months. To study effect of long-term voluntary exercise in AD, the 5xFAD mouse model of AD and their wild-type (WT) littermates at the age of 1.5 months were utilized. Mice from the voluntary exercise group had access to a running wheel for 6 months. We evaluated long-term exercise effect on aging in skeletal muscle and on AD in skeletal muscle, plasma and brain by variety of biochemical measurements. The impact of exercise on cognition in WT and 5xFAD mice were assessed by battery of behavioural tests. Histological measurements were used to assess the impact of long-term physical exercise on AD pathology. Morphological and colocalization analysis was performed to evaluate the involvement of astrocyte in exercise-induced beneficial effect in 5xFAD mice.
The doctoral dissertation of Irina Belaya, Master of Science, entitled Exercise-induced cellular and molecular alterations in aging and Alzheimer’s disease will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Professor Alexei Verkhratsky of the University of Manchester, and the Custos will be Associate Professor Katja Kanninen of the University of Eastern Finland. The public examination will be held in English and it will be streamed online.
