@article{HagoortVuillermeHortobagyietal.2022, author = {Hagoort, Iris and Vuillerme, Nicolas and Hortob{\´a}gyi, Tibor and Lamoth, Claudine J. C.}, title = {Outcome-dependent effects of walking speed and age on quantitative and qualitative gait measures}, series = {Gait \& posture}, volume = {93}, journal = {Gait \& posture}, publisher = {Elsevier}, address = {Clare}, issn = {0966-6362}, doi = {10.1016/j.gaitpost.2022.01.001}, pages = {39 -- 46}, year = {2022}, abstract = {Background: Walking speed predicts many clinical outcomes in old age. However, a comprehensive assessment of how walking speed affects accelerometer based quantitative and qualitative gait measures in younger and older adults is lacking. Research question: What is the relationship between walking speed and quantitative and qualitative gait outcomes in younger and older adults? Methods: Younger (n = 27, age: 21.6) and older participants (n = 27, age: 69.5) completed 340 steps on a treadmill at speeds of 0.70 to a maximum of 1.75 m.s(-1). We used generalized additive mixed models to determine the relationship between walking speed and quantitative (stride length, stride time, stride frequency and their variability) and qualitative (stride regularity, stability, smoothness, symmetry, synchronization, predictability) gait measures extracted from trunk accelerations. Results: The type of relationship between walking speed and the majority of gait measures (quantitative and qualitative) was characterized as logarithmic, with more prominent speed-effects at speeds below 1.20 m.s(-1). Changes in quantitative measures included shorter strides, longer stride times, and a lower stride frequency, with more variability at lower speeds independent of age. For qualitative measures, we found a decrease in gait symmetry, stability and regularity in all directions with decreasing speeds, a decrease in gait predictability (Vertical, V, anterior-posterior, AP) and stronger gait synchronization (AP-mediolateral, ML, AP-V), and direction dependent effects of gait smoothness, which decreased in V direction, but increased in AP and ML directions with decreasing speeds. We found outcome-dependent effects of age on the quantitative and qualitative gait measures, with either no differences between age-groups, age-related differences that existed regardless of speed, and age-related differences in the type of relationship with walking speed. Significance: The relationship between walking speed and quantitative and qualitative gait measures, and the effects of age on this relationship, depends on the type of gait measure studied.}, language = {en} } @article{HortobagyiVetrovskyBalbimetal.2022, author = {Hortob{\´a}gyi, Tibor and Vetrovsky, Tomas and Balbim, Guilherme Moraes and Sorte Silva, Narlon Cassio Boa and Manca, Andrea and Deriu, Franca and Kolmos, Mia and Kruuse, Christina and Liu-Ambrose, Teresa and Radak, Zsolt and Vaczi, Mark and Johansson, Hanna and Rocha dos Santos, Paulo Cezar and Franzen, Erika and Granacher, Urs}, title = {The impact of aerobic and resistance training intensity on markers of neuroplasticity in health and disease}, series = {Ageing research reviews : ARR}, volume = {80}, journal = {Ageing research reviews : ARR}, publisher = {Elsevier}, address = {Clare}, issn = {1568-1637}, doi = {10.1016/j.arr.2022.101698}, pages = {18}, year = {2022}, abstract = {Objective: To determine the effects of low- vs. high-intensity aerobic and resistance training on motor and cognitive function, brain activation, brain structure, and neurochemical markers of neuroplasticity and the association thereof in healthy young and older adults and in patients with multiple sclerosis, Parkinson's disease, and stroke. Design: Systematic review and robust variance estimation meta-analysis with meta-regression. Data sources: Systematic search of MEDLINE, Web of Science, and CINAHL databases. Results: Fifty studies with 60 intervention arms and 2283 in-analyses participants were included. Due to the low number of studies, the three patient groups were combined and analyzed as a single group. Overall, low- (g=0.19, p = 0.024) and high-intensity exercise (g=0.40, p = 0.001) improved neuroplasticity. Exercise intensity scaled with neuroplasticity only in healthy young adults but not in healthy older adults or patient groups. Exercise-induced improvements in neuroplasticity were associated with changes in motor but not cognitive outcomes. Conclusion: Exercise intensity is an important variable to dose and individualize the exercise stimulus for healthy young individuals but not necessarily for healthy older adults and neurological patients. This conclusion warrants caution because studies are needed that directly compare the effects of low- vs. high-intensity exercise on neuroplasticity to determine if such changes are mechanistically and incrementally linked to improved cognition and motor function.}, language = {en} } @article{HeroldTheobaldGronwaldetal.2022, author = {Herold, Fabian and Theobald, Paula and Gronwald, Thomas and Rapp, Michael A. and M{\"u}ller, Notger Germar}, title = {Going digital - a commentary on the terminology used at the intersection of physical activity and digital health}, series = {European review of aging and physical activity}, volume = {19}, journal = {European review of aging and physical activity}, publisher = {Springer}, address = {Berlin ; Heidelberg}, issn = {1861-6909}, doi = {10.1186/s11556-022-00296-y}, pages = {7}, year = {2022}, abstract = {In recent years digital technologies have become a major means for providing health-related services and this trend was strongly reinforced by the current Coronavirus disease 2019 (COVID-19) pandemic. As it is well-known that regular physical activity has positive effects on individual physical and mental health and thus is an important prerequisite for healthy aging, digital technologies are also increasingly used to promote unstructured and structured forms of physical activity. However, in the course of this development, several terms (e.g., Digital Health, Electronic Health, Mobile Health, Telehealth, Telemedicine, and Telerehabilitation) have been introduced to refer to the application of digital technologies to provide health-related services such as physical interventions. Unfortunately, the above-mentioned terms are often used in several different ways, but also relatively interchangeably. Given that ambiguous terminology is a major source of difficulty in scientific communication which can impede the progress of theoretical and empirical research, this article aims to make the reader aware of the subtle differences between the relevant terms which are applied at the intersection of physical activity and Digital Health and to provide state-of-art definitions for them.}, language = {en} } @article{HeinzelLorenzQuynhLamDuongetal.2017, author = {Heinzel, Stephan and Lorenz, Robert C. and Quynh-Lam Duong, and Rapp, Michael A. and Deserno, Lorenz}, title = {Prefrontal-parietal effective connectivity during working memory in older adults}, series = {Neurobiology of Aging}, volume = {57}, journal = {Neurobiology of Aging}, publisher = {Elsevier}, address = {New York}, issn = {0197-4580}, doi = {10.1016/j.neurobiolaging.2017.05.005}, pages = {18 -- 27}, year = {2017}, abstract = {Theoretical models and preceding studies have described age-related alterations in neuronal activation of frontoparietal regions in a working memory (WM)load-dependent manner. However, to date, underlying neuronal mechanisms of these WM load-dependent activation changes in aging remain poorly understood. The aim of this study was to investigate these mechanisms in terms of effective connectivity by application of dynamic causal modeling with Bayesian Model Selection. Eighteen healthy younger (age: 20-32 years) and 32 older (60-75 years) participants performed an n-back task with 3 WM load levels during functional magnetic resonance imaging (fMRI). Behavioral and conventional fMRI results replicated age group by WM load interactions. Importantly, the analysis of effective connectivity derived from dynamic causal modeling, indicated an age-and performance-related reduction in WM load-dependent modulation of connectivity from dorsolateral prefrontal cortex to inferior parietal lobule. This finding provides evidence for the proposal that age-related WM decline manifests as deficient WM load-dependent modulation of neuronal top-down control and can integrate implications from theoretical models and previous studies of functional changes in the aging brain.}, language = {en} } @article{NowotnyCastroHugoetal.2018, author = {Nowotny, Kerstin and Castro, Jose Pedro and Hugo, Martin and Braune, Sabine and Weber, Daniela and Pignitter, Marc and Somoza, Veronika and Bornhorst, Julia and Schwerdtle, Tanja and Grune, Tilman}, title = {Oxidants produced by methylglyoxal-modified collagen trigger ER stress and apoptosis in skin fibroblasts}, series = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research}, volume = {120}, journal = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research}, publisher = {Elsevier}, address = {New York}, issn = {0891-5849}, doi = {10.1016/j.freeradbiomed.2018.03.022}, pages = {102 -- 113}, year = {2018}, abstract = {Methylglyoxal (MG), a highly reactive dicarbonyl, interacts with proteins to form advanced glycation end products (AGEs). AGEs include a variety of compounds which were shown to have damaging potential and to accumulate in the course of different conditions such as diabetes mellitus and aging. After confirming collagen as a main target for MG modifications in vivo within the extracellular matrix, we show here that MG-collagen disrupts fibroblast redox homeostasis and induces endoplasmic reticulum (ER) stress and apoptosis. In particular, MG-collagen-induced apoptosis is associated with the activation of the PERK-eIF2 alpha pathway and caspase-12. MG-collagen contributes to altered redox homeostasis by directly generating hydrogen peroxide and oxygen-derived free radicals. The induction of ER stress in human fibroblasts was confirmed using collagen extracts isolated from old mice in which MG-derived AGEs were enriched. In conclusion, MG-derived AGEs represent one factor contributing to diminished fibroblast function during aging.}, language = {en} } @article{HortobagyiUematsuSandersetal.2018, author = {Hortobagyi, Tibor and Uematsu, Azusa and Sanders, Lianne and Kliegl, Reinhold and Tollar, Jozsef and Moraes, Renato and Granacher, Urs}, title = {Beam Walking to Assess Dynamic Balance in Health and Disease}, series = {Gerontology}, volume = {65}, journal = {Gerontology}, number = {4}, publisher = {Karger}, address = {Basel}, issn = {0304-324X}, doi = {10.1159/000493360}, pages = {332 -- 339}, year = {2018}, abstract = {Background: Dynamic balance keeps the vertical projection of the center of mass within the base of support while walking. Dynamic balance tests are used to predict the risks of falls and eventual falls. The psychometric properties of most dynamic balance tests are unsatisfactory and do not comprise an actual loss of balance while walking. Objectives: Using beam walking distance as a measure of dynamic balance, the BEAM consortium will determine the psychometric properties, lifespan and patient reference values, the relationship with selected "dynamic balance tests," and the accuracy of beam walking distance to predict falls. Methods: This cross-sectional observational study will examine healthy adults in 7 decades (n = 432) at 4 centers. Center 5 will examine patients (n = 100) diagnosed with Parkinson's disease, multiple sclerosis, stroke, and balance disorders. In test 1, all participants will be measured for demographics, medical history, muscle strength, gait, static balance, dynamic balance using beam walking under single (beam walking only) and dual task conditions (beam walking while concurrently performing an arithmetic task), and several cognitive functions. Patients and healthy participants age 50 years or older will be additionally measured for fear of falling, history of falls, miniBESTest, functional reach on a force platform, timed up and go, and reactive balance. All participants age 50 years or older will be recalled to report fear of falling and fall history 6 and 12 months after test 1. In test 2, seven to ten days after test 1, healthy young adults and age 50 years or older (n = 40) will be retested for reliability of beam walking performance. Conclusion: We expect to find that beam walking performance vis-{\`a}-vis the traditionally used balance outcomes predicts more accurately fall risks and falls. Clinical Trial Registration Number: NCT03532984.}, language = {en} } @article{FernandoDrescherNowotnyetal.2018, author = {Fernando, Raquel and Drescher, Cathleen and Nowotny, Kerstin and Grune, Tilman and Castro, Jose Pedro}, title = {Impaired proteostasis during skeletal muscle aging}, series = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research}, volume = {132}, journal = {Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research}, publisher = {Elsevier}, address = {New York}, issn = {0891-5849}, doi = {10.1016/j.freeradbiomed.2018.08.037}, pages = {58 -- 66}, year = {2018}, abstract = {Aging is a complex phenomenon that has detrimental effects on tissue homeostasis. The skeletal muscle is one of the earliest tissues to be affected and to manifest age-related changes such as functional impairment and the loss of mass. Common to these alterations and to most of tissues during aging is the disruption of the proteostasis network by detrimental changes in the ubiquitin-proteasomal system (UPS) and the autophagy-lysosomal system (ALS). In fact, during aging the accumulation of protein aggregates, a process mainly driven by increased levels of oxidative stress, has been observed, clearly demonstrating UPS and ALS dysregulation. Since the UPS and ALS are the two most important pathways for the removal of misfolded and aggregated proteins and also of damaged organelles, we provide here an overview on the current knowledge regarding the connection between the loss of proteostasis and skeletal muscle functional impairment and also how redox regulation can play a role during aging. Therefore, this review serves for a better understanding of skeletal muscle aging in regard to the loss of proteostasis and how redox regulation can impact its function and maintenance.}, language = {en} } @article{FernandoDrescherDeubeletal.2018, author = {Fernando, Raquel and Drescher, Cathleen and Deubel, Stefanie and Jung, Tobias and Ost, Mario and Klaus, Susanne and Grune, Tilman and Castro, Jose Pedro}, title = {Low proteasomal activity in fast skeletal muscle fibers is not associated with increased age-related oxidative damage}, series = {Experimental gerontology}, volume = {117}, journal = {Experimental gerontology}, publisher = {Elsevier}, address = {Oxford}, issn = {0531-5565}, doi = {10.1016/j.exger.2018.10.018}, pages = {45 -- 52}, year = {2018}, abstract = {The skeletal muscle is a crucial tissue for maintaining whole body homeostasis. Aging seems to have a disruptive effect on skeletal muscle homeostasis including proteostasis. However, how aging specifically impacts slow and fast twitch fiber types remains elusive. Muscle proteostasis is largely maintained by the proteasomal system. Here we characterized the proteasomal system in two different fiber types, using a non-sarcopenic aging model. By analyzing the proteasomal activity and amount, as well as the polyubiquitinated proteins and the level of protein oxidation in Musculus soleus (Sol) and Musculus extensor digitorum longus (EDL), we found that the slow twitch Sol muscle shows an overall higher respiratory and proteasomal activity in young and old animals. However, especially during aging the fast twitch EDL muscle reduces protein oxidation by an increase of antioxidant capacity. Thus, under adaptive non-sarcopenic conditions, the two fibers types seem to have different strategies to avoid age-related changes.}, language = {en} } @article{MaBalazadehMuellerRoeber2019, author = {Ma, Xuemin and Balazadeh, Salma and Mueller-Roeber, Bernd}, title = {Tomato fruit ripening factor NOR controls leaf senescence}, series = {Journal of experimental botany}, volume = {70}, journal = {Journal of experimental botany}, number = {10}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0022-0957}, doi = {10.1093/jxb/erz098}, pages = {2727 -- 2740}, year = {2019}, abstract = {NAC transcription factors (TFs) are important regulators of expressional reprogramming during plant development, stress responses, and leaf senescence. NAC TFs also play important roles in fruit ripening. In tomato (Solanum lycopersicum), one of the best characterized NACs involved in fruit ripening is NON-RIPENING (NOR), and the non-ripening (nor) mutation has been widely used to extend fruit shelf life in elite varieties. Here, we show that NOR additionally controls leaf senescence. Expression of NOR increases with leaf age, and developmental as well as dark-induced senescence are delayed in the nor mutant, while overexpression of NOR promotes leaf senescence. Genes associated with chlorophyll degradation as well as senescence-associated genes (SAGs) show reduced and elevated expression, respectively, in nor mutants and NOR overexpressors. Overexpression of NOR also stimulates leaf senescence in Arabidopsis thaliana. In tomato, NOR supports senescence by directly and positively regulating the expression of several senescence-associated genes including, besides others, SlSAG15 and SlSAG113, SlSGR1, and SlYLS4. Finally, we find that another senescence control NAC TF, namely SlNAP2, acts upstream of NOR to regulate its expression. Our data support a model whereby NAC TFs have often been recruited by higher plants for both the control of leaf senescence and fruit ripening.}, language = {en} } @article{GohlkeZagoriyInostrozaetal.2019, author = {Gohlke, Sabrina and Zagoriy, Vyacheslav and Inostroza, Alvaro Cuadros and Meret, Michael and Mancini, Carola and Japtok, Lukasz and Schumacher, Fabian and Kuhlow, Doreen and Graja, Antonia and Stephanowitz, Heike and J{\"a}hnert, Markus and Krause, Eberhard and Wernitz, Andreas and Petzke, Klaus-Juergen and Sch{\"u}rmann, Annette and Kleuser, Burkhard and Schulz, Tim Julius}, title = {Identification of functional lipid metabolism biomarkers of brown adipose tissue aging}, series = {Molecular Metabolism}, volume = {24}, journal = {Molecular Metabolism}, publisher = {Elsevier}, address = {Amsterdam}, issn = {2212-8778}, doi = {10.1016/j.molmet.2019.03.011}, pages = {1 -- 17}, year = {2019}, abstract = {Objective: Aging is accompanied by loss of brown adipocytes and a decline in their thermogenic potential, which may exacerbate the development of adiposity and other metabolic disorders. Presently, only limited evidence exists describing the molecular alterations leading to impaired brown adipogenesis with aging and the contribution of these processes to changes of systemic energy metabolism. Methods: Samples of young and aged murine brown and white adipose tissue were used to compare age-related changes of brown adipogenic gene expression and thermogenesis-related lipid mobilization. To identify potential markers of brown adipose tissue aging, non-targeted proteomic and metabolomic as well as targeted lipid analyses were conducted on young and aged tissue samples. Subsequently, the effects of several candidate lipid classes on brown adipocyte function were examined. Results: Corroborating previous reports of reduced expression of uncoupling protein-1, we observe impaired signaling required for lipid mobilization in aged brown fat after adrenergic stimulation. Omics analyses additionally confirm the age-related impairment of lipid homeostasis and reveal the accumulation of specific lipid classes, including certain sphingolipids, ceramides, and dolichols in aged brown fat. While ceramides as well as enzymes of dolichol metabolism inhibit brown adipogenesis, inhibition of sphingosine 1-phosphate receptor 2 induces brown adipocyte differentiation. Conclusions: Our functional analyses show that changes in specific lipid species, as observed during aging, may contribute to reduced thermogenic potential. They thus uncover potential biomarkers of aging as well as molecular mechanisms that could contribute to the degradation of brown adipocytes, thereby providing potential treatment strategies of age-related metabolic conditions.}, language = {en} }