Title Promoter Affiliations Abstract "Healthy and active aging: effects of a cognitively enriched walking intervention on cognitive function in older adults and the role of expectations regarding aging for health behaviors" "Greet Cardon, Jannique van Uffelen" "Physical Activity, Sports & Health Research Group" "This PhD will contribute to the understanding of healthy and active aging, all the more important given the increasing number of older adults in the population. Dementia currently affects more than 47 million people worldwide, is forecasted to triple by 2050 and has been reported to be one of the most costly disorders in Belgium.There is good scientific evidence that the cognitive impairments associated with the development of dementia can be lessened or even reversed because of the plasticity of the brain (rewiring). Recent research has shown that physical activity combined with performing cognitively challenging tasks is a very potent way to induce this rewiring of the brain that can enable people to improve cognitive functions. Yet, so far, these studies are mainly limited to controlled laboratory conditions. In this project, we will translate this laboratory-based evidence into a real-life, low-cost intervention that is easily accessible and tailored to the needs of the aging population and evaluate the effectiveness of this newly developed intervention.In this research project, we will conduct a pilot trial to gain insights on the feasibility of the cognitively enriched walking program (also referred to as “Brain Walks”) for older adults and for coaches supervising the walks. This program was developed by our research group in collaboration with older adults, health professionals and scientists. In my PhD, we will finalize the intervention based on the results of a mixed-method pilot study. Following this, we will examine the added value of enriching physical activity with cognitive tasks in improving cognition of older adults by conducting a nine-month community-based randomized controlled trial. We will also examine the longer term effectiveness in a follow-up study six months after the program.A disadvantage of (real-life) intervention studies, however, is that only the people who participate can experience the benefits. Furthermore, people also decide for themselves whether or not to engage in certain healthy behaviors, such as physical activity. As such, despite the proven benefits for cognitive, physical and mental health, only 27.5% of adults worldwide engage in the minimum WHO recommended amount of physical (aerobic) activity for health benefits (i.e. PA guidelines), and it is known that prevalence of insufficient physical activity (i.e. not meeting PA guidelines) increases with age.One important factor that may influence whether or not older adults engage in health promoting behavior are their ‘expectations regarding aging (ERA)’, the beliefs people hold as to how well they will age physically and cognitively. Research has shown that low ERA were associated with poorer general, physical, mental and cognitive health and lower engagement in health promoting behaviors. Moreover, researchers have proposed a bi-directional relationship between ERA and health. In this project, we will address this topic by providing an updated synthesis of the existing research on ERA and the association with health behaviors in older adults. Furthermore, we will include ERA as a secondary outcome measure for the cognitively enriched walking program RCT and follow-up study. This way, we aim to develop a better understanding of the influence of an exercise intervention and a combined intervention targeting both physical and cognitive activity on the ERA of older adults." "The aging T-Cell immune system, cognitive aging and Alzheimer's disease" "Rik Vandenberghe" "Laboratory for Cognitive Neurology" "Alzheimer disease (AD) is a complex disease characterized by amyloid plaques, neurofibrillary tangles, and neuronal and synaptic loss. Genetic factors play a significant role, with Apolipoprotein E4 (APOE4) carriership being the strongest genetic risk factor. Further loci from Genome Wide association studies (GWAS) suggest that immune system dysregulation is a critical feature of AD, with alterations in the adaptive immune system leading to both protective and destructive downstream effects. However, there is wide variability within AD patients in their adaptive immunity phenotype which may partly explain the heterogeneity within Alzheimer disease as a multidimensional brain disease instead of a monolithic disorder. We aim to examine the longitudinal changes in adaptive immunity in peripheral blood in AD across the disease spectrum and how they reflect cognitive decline as well as PET- and blood-based changes in brain proteostasis and neuroinflammation. We will employ and add on to the ongoing longitudinal collection of imaging, serum, plasma, and PBMC in the full FPACK and ARCK cohort. We hypothesize that there are amyloid-dependent and amyloid-independent mechanisms of brain aging that are linked with immune dysregulation, namely decreases in CD4 TEM/TCM and increases in CD4 TEMRA immunophenotypes and age-related increases in CD8 TEMRA cells respectively. Changes in peripheral adaptive immunity most likely become proportionally more pronounced as the disease progresses." "Why can't the aging brain adapt to the aging body?" "Jean-Jacques Orban de Xivry" "Movement Control & Neuroplasticity Research Group" "During aging, the ability of people to accurately control their movements deteriorates partially due to a change in the properties of the body (e.g., muscles, tendons). While the brain of young adults would be able to cope with such a change in the body, the brain of elderly people cannot. Here, the mechanisms of motor adaptation will be investigated in detail in elderly adults in order to understand why the brain cannot adapt to the aging body. This impairment is probably linked to the fact that many cells in the brain of elderly people become non-functional. Interestingly, transcranial direct current stimulation (tDCS) can recruit non-functional cells. Therefore, I will investigate the ability of tDCS to recruit the non-functional cells of the aging brain in order to temporarily improve motor function in elderly people. The effect of tDCS on brain activity will be monitored via functional magnetic resonance imaging in order to gain insights into the neural substrates of tDCS-mediated improvements in motor function. While tDCS will never fully restore motor functions in elderly adults, it could temporarily help them to regain some functions that would be later maintained via other rehabilitation programs." "Neural temporal processing in the aging auditory system: disentangling effects of aging and peripheral hearing loss" "Astrid van Wieringen" "Research Group Experimental Oto-rhino-laryngology" "Good speech perception skills are important for communication and social integration. Many persons, however, suffer from impaired speech perception in everyday, noisy listening situations, which causes them to avoid or miss out on social events, thereby affecting their quality of life. There is general consensus that difficulties in speech perception result from hearing impairment, age, and cognitive problems. Nevertheless, it remains unclear to what extent each of these three factors act upon speech perception. This lack of knowledge can be attributed to the interrelatedness between hearing impairment, age, and cognitive declines, which makes it difficult to investigate their differential contributions to difficulties in speech perception. Yet, such knowledge is needed to develop effective intervention strategies for remediating these highly prevalent difficulties.The aim of the present research was to unravel the differential impact of hearing impairment and age on speech perception. Therefore, a specific research design was applied. We recruited persons of three age categories, i.e., young (20-30 years), middle-aged (50-60 years), and older (70-80 years), who were either normal-hearing (NH) or hearing-impaired (HI). All participants passed a sensitive cognitive screening, indicating that they had normal cognitive capacities. In this way, we minimized confounding effects of cognition. By comparing outcomes among the three NH age groups, on the one hand, and between NH and HI similar-aged adults, on the other hand, we could investigate effects of age and hearing impairment, respectively.We performed behavioral speech tests and electrophysiological measurements to gain insight into the extent as well as the nature of the declining effects of age and hearing impairment on speech perception. Speech perception performance was evaluated in different masking noises to verify whether the impact of age and/or hearing impairment depends on the type of background noise. As for the electrophysiological measurements, we investigated neural temporal processing in the auditory brain, and neural envelope encoding in particular. The slowly varying temporal envelope of speech is known to drive speech perception and the envelope modulations are encoded by synchronized neural oscillatory activity along the central auditory pathway. In order to look into this neural envelope encoding, we recorded auditory steady-state responses (ASSRs) to speech-related acoustic modulations. The degree of neural envelope encoding was examined all along the auditory pathway, from the brainstem up to the cortex. The functional hemispheric asymmetry, i.e., asymmetrical processing of specific modulation frequencies towards the left or the right hemisphere, which is an intrinsic aspect of speech processing, was investigated as well.The present research demonstrates that speech perception in noise declines by middle age and decreases further on to older age, independent of hearing sensitivity. We also show that the declining effect of hearing impairment is the same at a young, middle, and older age. The declining effects of age and hearing impairment are most pronounced in cognitively demanding background noises (informational masking). Moreover, in such background noises, both hearing impairment and age account for a significant part of the speech perception difficulties of HI aging persons, whereas hearing impairment is the predominant degrading factor in background noises that merely cause energetic masking.Our electrophysiological measurements reveal that age as well as hearing impairment are characterized by changes in the neural encoding of the temporal envelope in both subcortical and cortical auditory regions. As for the factor age, cortical neural envelope encoding increases and the subcortical encoding decreases with advancing age, irrespective of peripheral hearing sensitivity. Furthermore, at an older age, there is a reduction in functional hemispheric asymmetry. As for hearing impairment, we demonstrate that it is inherently related to enhanced neural envelope encoding from the brainstem up to the cortex – most saliently when audibility is corrected for – at a young and middle age. No such neural enhancement is apparent in HI older adults. Yet, hearing impairment at an older age (presbycusis) is characterized by a functional hemispheric asymmetry that is not apparent in older adults who have normal peripheral hearing sensitivity.Finally, we performed regression analyses to determine whether the age- and hearing-related changes in speech perception performance can be explained by the observed changes in neural temporal processing. Significant correlations were, indeed, identified. We show that enhanced neural envelope encoding in the auditory cortex is predictive of poor speech perception in NH adults. In HI adults, enhanced neural envelope encoding in the brainstem is associated with inferior speech perception.This doctoral research clarifies the differential contributions of age and hearing impairment to difficulties in speech perception and provides a detailed characterization of the impact of age and hearing impairment on neural envelope encoding in the auditory brain. Moreover, the observed correspondences between neural envelope encoding and impaired speech perception yield promising directions for developing advanced intervention strategies to improve speech perception skills, and, in turn, quality of life.   " "Closed-Loop Acoustic Stimulation during Sleep to enhance motor memory consolidation in Aging" "Genevieve Albouy" "Department of Movement Sciences" "Research has consistently demonstrated that older adults have difficulties consolidating recently learned movements into robust motor memories. This impairment undoubtedly contributes to the movement deficits emerging with healthy aging and hinders rehabilitative strategies. As consolidation is known to be facilitated by sleep, these movement-related deficits partially result from age-associated degradations in sleep characteristics.Accordingly, the project CLASSy Aging (Closed-Loop Acoustic Stimulation during Sleep to enhance motor memory consolidation in Aging) aims to optimize sleep-related motor memory consolidation in healthy older adults. Specifically, during a post-learning nap, I will use forefront real-time electroencephalographic (EEG) analyses to reactivate memories via Targeted Memory Reactivation time-locked to neuroplasticity-related physiological events of interest (i.e., sleep spindles and slow oscillations). This project will use a novel and sophisticated approach designed to boost sleep-dependent consolidation and minimize previously observed aging-related deficits. I will unravel the neural correlates of the memory reactivation process using high-density EEG during post-learning sleep and the stimulation-enhanced neuroplasticity processes during task practice using functional Magnetic Resonance Imaging (MRI). This project uses a comprehensive approach as the brain will be imaged at different phases of the memory formation (i.e., learning, consolidation and retest) making use of cutting-edge neuroimaging analyses (univariate and multivariate MRI analyses, sources localization of hdEEG signal) tailored to each of these phases. This ambitious, yet feasible, multimodal neuroimaging project will provide significant insights into motor memory processes. It will offer new avenues to amplify neuroplasticity, alleviate motor deficits, and increase well-being in not only healthy aging, but ultimately in those with neurological conditions." "Circulating extracellular vesicle cargo perturbations in skeletal muscle chronic regeneration and aging" "Maurilio Sampaolesi" "Stem Cell and Developmental Biology" "In thirty years, the global population of seniors (60 years old) is estimated to more than double its size. This trend will affect the number of patients affected by sarcopenia, a syndrome characterized by loss of muscle mass and strength without body mass reduction.Various factors contribute to sarcopenia, including diet, chronic illness, physical activity and physiological ageing, leading to poor quality of life. The main underlying cause is an imbalance in protein synthesis and degradation that leads to muscle atrophy. We have already demonstrated how ageing negatively impacts the regenerative potential of human mesoangioblasts, muscle stem cells that contribute to repairing muscle fibres in adulthood. In addition, we and other groups proved that small non-coding RNAs (miRNAs) are able to modulate muscle mass and function and can be delivered as extracellular vesicle cargoes. Our working hypothesis is that ageing muscles have a different miRNA signature compared to young muscles and that by modulating this signature we can recover old muscle features. Therefore, we will apply miRNAs-based therapy to murine models of sarcopenia, assessing functional regeneration in skeletal muscles. We will therefore investigate inter- and intrapopulation heterogeneity during muscle ageing via single-cell RNA sequencing. Finally, we will test conserved miRNAs on old human muscle stem cells to revert the hallmarks of ageing." "Unraveling the role of retinal imaging as a clinical tool in evaluating accelerated aging in congenital heart disease" "Philip Moons" "Academic Centre for Nursing and Midwifery" "Congenital heart disease (CHD) used to be a predominantly lethal condition. Improved life expectancy yield that most patients with CHD can survive into adulthood, to date. However, survivors often develop morbidities that suggest accelerated aging, because several agerelatedmorbidities occur more often and at an earlier age in these patients. We need to quantify and understand disparities in chronological and biological age in adults with CHD. Furthermore, it is important to have non-invasive tools at hand that can evaluate this age gap.Retinal imaging could become a useful clinical tool to be used for this purpose, if proven valuable." "Associations between immunosenescence and cellular senescence as determinants of aging and pathology." "Immunology & Infection, Center of Molecular Immunology" "Ageing is accompanied by a functional decline of our immune system, called immunosenescence. In parallel, with advancing age, there is an accumulation of senescent cells with limited proliferative capacity throughout the body. Although immunosenescence and cellular senescence share some common features, the relationship between these two phenomena is still poorly understood. The aim of this project is to determine the association between immunosenescence and cellular senescence as determinants of aging and pathology. To achieve this, we identify the expression of cellular senescence and immunosenescence markers in immune cells from healthy donors between 20 and 99 years old. We study European as well as Caribbean donors, to detect common ageing pathways and identify distinct ageing patterns in these populations. We use immune cells of centenarians as a model of successful ageing, and immune cells from MS patients as a model for premature immune ageing. The results gathered provide a human encyclopedia with the timing and expression patterns of (immune-)senescence markers amongst different immune cell subsets. We use these data to determine the association between immune ageing and clinical status. Ultimately, we build an ""aging clock"" for the estimation of the biological age of the immune system. This knowledge is necessary to design adequate therapies that ameliorate the worldwide increase in ageassociated diseases." "Numerical Cognition and Aging" "Wim Fias" "Department of Experimental clinical and health psychology, Department of Experimental psychology" "Numerical cognition is an essential everyday life skill and encompasses a host of number-related cognitive functions. As with most mental abilities, numerical cognition changes over time. However, while the literature has paid much attention to the early development of numerical cognition, studies on elderly remain scarce. The current evidence on aging is not unequivocal. Moreover, current literature on aging in numerical cognition is rather descriptive and not explicitly framed in theories of cognitive aging. The triple code model and the HAROLD hypothesis respectively postulate predictions on the laterality of processes underlying numerical processing and compensational changes in laterality over age. Combining those two theories results in some unanswered questions, as current literature provides no clarity on how numerical task performance and underlying laterality are related to one another over age. Therefore, this project aims to investigate underlying brain laterality using Functional Transcranial Doppler Sonography (fTCDS), as this may prove a promising avenue to address this issue and to come to a better understanding of aging effects in mathematical cognition. In case aging impairs numerical task performance, whether or not accompanied by maladaptive underlying laterality, it would be favorable to counteract this impairment. Therefore, this project aims to investigate how training affects both numerical task performance and underlying laterality in elderly." "Identification of endotrophin as a new key player in vascular aging." "Lynn Roth" "Physiopharmacology (PHYSPHAR)" "Age-related diseases such as cardiovascular (CV) disease have a substantial impact on our quality of life. The aging vasculature is characterized by arterial stiffness, which is an independent predictor of CV complications. There is accumulating evidence that loss of autophagy, a cellular housekeeping mechanism, facilitates vascular aging. Recent literature describes that endotrophin (ETP) serum levels (a cleavage product of COL6A3) are associated with arterial stiffness and CV events. Furthermore, we have observed that autophagy deficiency in vascular smooth muscle cells (VSMCs) results in a higher expression of ETP. However, an in-depth analysis of the link between ETP and autophagy and how this affects vascular aging is lacking. Therefore, we aim to investigate if ETP accelerates vascular aging and whether it contributes to the detrimental effects of autophagy deficiency in VSMCs. This will answer three research questions: (1) What are the biological effects of ETP on vascular cell function, and do they explain some of the detrimental effects of VSMC autophagy deficiency? (2) Can ETP contribute to accelerated vascular aging in mice? (3) Does defective VSMC autophagy exert its main effects on the vascular wall through enhanced expression of ETP? Overall, this project will bring us one step closer in understanding how an age-related decline in autophagy can lead to CV disease and might result in identifying ETP as a novel therapeutic target."