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Aging is a one-way process associated with profound structural and functional changes in the organism. Indeed, the neuromuscular system undergoes a wide remodeling, which involves muscles, fascia, and the central and peripheral nervous systems. As a result, intrinsic features of tissues, as well as their functional and structural coupling, are affected and a decline in overall physical performance occurs. Evidence from the scientific literature demonstrates that senescence is associated with increased stiffness and reduced elasticity of fascia, as well as loss of skeletal muscle mass, strength, and regenerative potential. The interaction between muscular and fascial structures is also weakened. As for the nervous system, aging leads to motor cortex atrophy, reduced motor cortical excitability, and plasticity, thus leading to accumulation of denervated muscle fibers. As a result, the magnitude of force generated by the neuromuscular apparatus, its transmission along the myofascial chain, joint mobility, and movement coordination are impaired. In this review, we summarize the evidence about the deleterious effect of aging on skeletal muscle, fascial tissue, and the nervous system. In particular, we address the structural and functional changes occurring within and between these tissues and discuss the effect of inflammation in aging. From the clinical perspective, this article outlines promising approaches for analyzing the composition and the viscoelastic properties of skeletal muscle, such as ultrasonography and elastography, which could be applied for a better understanding of musculoskeletal modifications occurring with aging. Moreover, we describe the use of tissue manipulation techniques, such as massage, traction, mobilization as well as acupuncture, dry needling, and nerve block, to enhance fascial repair.
Due to the increasingly heterogeneous trajectories of aging, gerontology requires theoretical models and empirical methods that can meaningfully, reliably, and precisely describe, explain, and predict causes and effects within the aging process, considering particular contexts and situations. Human behavior occurs in contexts; nevertheless, situational changes are often neglected in context-based behavior research. This article follows the tradition of environmental gerontology research based on Lawton’s Person-Environment-Interaction model (P-E model) and the theoretical developments of recent years. The authors discuss that, despite an explicit time component, current P-E models could be strengthened by focusing on detecting P-E interactions in various everyday situations. Enhancing Lawton’s original formula via a situationally based component not only changes the theoretical perspectives on the interplay between person and environment but also demands new data collection approaches in empirical environmental research. Those approaches are discussed through the example of collecting mobile data with smartphones. Future research should include the situational dimension to investigate the complex nature of person environment interactions.
Unmasking a temperature-dependent effect of the P. anserina i-AAA protease on aging and development
(2011)
Different molecular pathways involved in maintaining mitochondrial function are of fundamental importance to control cellular homeostasis. Mitochondrial i-AAA protease is part of such a surveillance system, and PaIAP is the putative ortholog in the fungal aging model Podospora anserina. Here, we investigate the role of PaIAP in aging and development. Deletion of the gene encoding PaIAP resulted in a specific phenotype. When incubated at 27°C, spore germination and fruiting body formation are not different from that of the corresponding wild-type strain. Unexpectedly, the lifespan of the deletion strain is strongly increased. In contrast, cultivation at an elevated temperature of 37°C leads to impairments in spore germination and fruiting body formation and to a reduced lifespan. The higher PaIAP abundance in wild-type strains of the fungus grown at elevated temperature and the phenotype of the deletion strain unmasks a temperature-related role of the protein. The protease appears to be part of a molecular system that has evolved to allow survival under changing temperatures, as they characteristically occur in nature.
Background: Scientifically evaluated cognitive intervention programs are essential to meet the demands of our increasingly aging society. Currently, one of the “hottest” topics in the field is the improvement of working memory function and its potential impact on overall cognition. The present study evaluated the efficacy of WOME (WOrking MEmory), a theory-based working memory training program, in a double-blind, placebo-controlled, and randomized controlled trial (www.drks.de, DRKS00013162).
Methods: N = 60 healthy older adults were allocated to (1) the WOME intervention, (2) an active low-level intervention, or (3) a passive control group. Overall, the intervention groups practiced twelve sessions of 45 min within 4 weeks of their respective training. Transfer effects were measured via an extensive battery of neuropsychological tests and questionnaires both pre-/post-training and at a 3-month follow-up.
Results: WOME led to a significant improvement in working memory function, demonstrated on a non-trained near transfer task and on two different composite scores with moderate to large effect sizes. In addition, we found some indication of relevant impact on everyday life. The effects were short-term rather than stable, being substantially diminished at follow-up with only little evidence suggesting long-term maintenance. No transfer effects on other cognitive functions were observed.
Conclusion: WOME is an appropriate and efficient intervention specifically targeting the working memory system in healthy older adults.
Trial Registration: German Clinical Trials Register (DRKS), Identifier: DRKS00013162.
Mitochondria are dynamic eukaryotic organelles involved in a variety of essential cellular processes including the generation of adenosine triphosphate (ATP) and reactive oxygen species as well as in the control of apoptosis and autophagy. Impairments of mitochondrial functions lead to aging and disease. Previous work with the ascomycete Podospora anserina demonstrated that mitochondrial morphotype as well as mitochondrial ultrastructure change during aging. The latter goes along with an age-dependent reorganization of the inner mitochondrial membrane leading to a change from lamellar cristae to vesicular structures. Particularly from studies with yeast, it is known that besides the F1Fo-ATP-synthase and the phospholipid cardiolipin also the “mitochondrial contact site and cristae organizing system” (MICOS) complex, existing of the Mic60- and Mic10-subcomplex, is essential for proper cristae formation. In the present study, we aimed to understand the mechanistic basis of age-related changes in the mitochondrial ultrastructure. We observed that MICOS subunits are coregulated at the posttranscriptional level. This regulation partially depends on the mitochondrial iAAA-protease PaIAP. Most surprisingly, we made the counterintuitive observation that, despite the loss of lamellar cristae and of mitochondrial impairments, the ablation of MICOS subunits (except for PaMIC12) leads to a pronounced lifespan extension. Moreover, simultaneous ablation of subunits of both MICOS subcomplexes synergistically increases lifespan, providing formal genetic evidence that both subcomplexes affect lifespan by different and at least partially independent pathways. At the molecular level, we found that ablation of Mic10-subcomplex components leads to a mitohormesis-induced lifespan extension, while lifespan extension of Mic60-subcomplex mutants seems to be controlled by pathways involved in the control of phospholipid homeostasis. Overall, our data demonstrate that both MICOS subcomplexes have different functions and play distinct roles in the aging process of P. anserina.
Digital technologies have gained vast relevance in postmodern societies and digital infrastructures are substantially integrated into the everyday lives of older people. This digitization is reframing the norms and practices of later life as well as the social construct of age itself. Despite the increasing amount of studies in the field of aging and technologies, it still lacks theorizing. This paper addresses this deficit, suggesting that the study of aging and technologies could profit from a comprehensive integration of theories from the sociology of aging, critical gerontology, and science-and-technology studies. We aim to make a theoretical contribution to this issue, asking: how is age being done in a digitized world? Applying a praxeological approach to aging and technologies, we firstly examine how theoretical and empirical work has constructed aging with technologies so far and identify its shortcomings. Some of this work so far lacks a proper consideration of social inequalities within these processes, whereas other studies lack a thorough consideration of materialities. Secondly, in an attempt to equally "praxeologize" and "materialize" the study of aging and technologies we develop a theoretical model that aims to overcome these shortcomings. In what we frame as a material praxeology of aging with technology, we are concerned with how age is being done through discursive formations, set into practice through social and material practices and involved in the (re)production of social inequalities. Enriching a Bordieuan terminology of social fields with notions of non-human agency, this praxeology is founded on three assumptions: (1) Social fields constitute the contexts in which age as a social phenomenon is being done with and through technologies (2) Human and non-human agents are equally involved in this process (3) The actions of the involved agents emerge from an agency distributed among them, and are structured through the power relations between them. Thirdly, we exemplify the application of this model by reference to a research project in the field of Active and Assistive Living.
Atherosclerosis and its sequelae, such as myocardial infarction and stroke, are the leading cause of death worldwide. Vascular endothelial cells (EC) play a critical role in vascular homeostasis and disease. Atherosclerosis as well as its independent risk factors including diabetes, obesity, and aging, are hallmarked by endothelial activation and dysfunction. Metabolic pathways have emerged as key regulators of many EC functions, including angiogenesis, inflammation, and barrier function, processes which are deregulated during atherogenesis. In this review, we highlight the role of glucose, fatty acid, and amino acid metabolism in EC functions during physiological and pathological states, specifically atherosclerosis, diabetes, obesity and aging.
The role of microglial cells in the pathogenesis of Alzheimer’s disease (AD) neurodegeneration is unknown. Although several works suggest that chronic neuroinflammation caused by activated microglia contributes to neurofibrillary degeneration, anti-inflammatory drugs do not prevent or reverse neuronal tau pathology. This raises the question if indeed microglial activation occurs in the human brain at sites of neurofibrillary degeneration. In view of the recent work demonstrating presence of dystrophic (senescent) microglia in aged human brain, the purpose of this study was to investigate microglial cells in situ and at high resolution in the immediate vicinity of tau-positive structures in order to determine conclusively whether degenerating neuronal structures are associated with activated or with dystrophic microglia. We used a newly optimized immunohistochemical method for visualizing microglial cells in human archival brain together with Braak staging of neurofibrillary pathology to ascertain the morphology of microglia in the vicinity of tau-positive structures. We now report histopathological findings from 19 humans covering the spectrum from none to severe AD pathology, including patients with Down’s syndrome, showing that degenerating neuronal structures positive for tau (neuropil threads, neurofibrillary tangles, neuritic plaques) are invariably colocalized with severely dystrophic (fragmented) rather than with activated microglial cells. Using Braak staging of Alzheimer neuropathology we demonstrate that microglial dystrophy precedes the spread of tau pathology. Deposits of amyloid-beta protein (A beta) devoid of tau-positive structures were found to be colocalized with non-activated, ramified microglia, suggesting that A beta does not trigger microglial activation. Our findings also indicate that when microglial activation does occur in the absence of an identifiable acute central nervous system insult, it is likely to be the result of systemic infectious disease. The findings reported here strongly argue against the hypothesis that neuroinflammatory changes contribute to AD dementia. Instead, they offer an alternative hypothesis of AD pathogenesis that takes into consideration: (1) the notion that microglia are neuron-supporting cells and neuroprotective; (2) the fact that development of non-familial, sporadic AD is inextricably linked to aging. They support the idea that progressive, aging-related microglial degeneration and loss of microglial neuroprotection rather than induction of microglial activation contributes to the onset of sporadic Alzheimer’s disease. The results have far-reaching implications in terms of reevaluating current treatment approaches towards AD.
Neural pattern similarity differentially relates to memory performance in younger and older adults
(2019)
Age-related memory decline is associated with changes in neural functioning, but little is known about how aging affects the quality of information representation in the brain. Whereas a long-standing hypothesis of the aging literature links cognitive impairments to less distinct neural representations in old age (“neural dedifferentiation”), memory studies have shown that overlapping neural representations of different studied items are beneficial for memory performance. In an electroencephalography (EEG) study, we addressed the question whether distinctiveness or similarity between patterns of neural activity supports memory differentially in younger and older adults. We analyzed between-item neural pattern similarity in 50 younger (19–27 years old) and 63 older (63–75 years old) male and female human adults who repeatedly studied and recalled scene–word associations using a mnemonic imagery strategy. We compared the similarity of spatiotemporal EEG frequency patterns during initial encoding in relation to subsequent recall performance. The within-person association between memory success and pattern similarity differed between age groups: For older adults, better memory performance was linked to higher similarity early in the encoding trials, whereas young adults benefited from lower similarity between earlier and later periods during encoding, which might reflect their better success in forming unique memorable mental images of the joint picture–word pairs. Our results advance the understanding of the representational properties that give rise to subsequent memory, as well as how these properties may change in the course of aging.
The hypothesis that oxidative stress plays a role in the pathogenesis of Alzheimer’s disease (AD) was tested by studying oxidative damage, acitvities of antioxidant enzymes and levels of reactive oxygen species (ROS) in several models. To this end, mouse models transgenic for mutant presenilin (PS1M146L) as well as mutant amyloid precursor protein (APP) and human post mortem brain tissue from sporadic AD patients and age-matched controls were studied. Aging leads to an upregulation of antioxidant enzyme activities of Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) in brains from C57BL/6J mice. Simultaneously, levels of lipid peroxidation products malondialdehyde MDA and 4-hydroxynonenal HNE were reduced. Additionally, pronounced gender effects were observed, as female mice display better protection against oxidative damage due to higher activity of GPx. Hence, antioxidant enzymes provide an important contribution to the protection against oxidative damage. In PS1M146L transgenic mice oxidative damage was only detectable in 19-22 months old mice, arguing for an additive effect of aging and the PS1 mutation. Both HNE levels in brain tissue as well as mitochondrial and cytosolic levels of ROS in splenic lymphocytes were increased in PS1M146L mice. Antioxidant defences were unaltered. In PDGF-APP and PDGF-APP/PS1 trangenic mice no changes in any of the parameters studied were observed in any age group. In contrast, Thy1-APP transgenic mice display oxidative damage as assessed by increased HNE levels. Reduced activity of Cu/Zn-SOD may explain this observation. Additionally, gender modified this effect, as female APP transgenic mice display higher b-secretase cleavage of APP and simultaneously increased HNE levels and reduced Cu/Zn-SOD activity earlier than male mice, i.e. from an age of 3 months and before the formation of Ab plaques. Reduced Cu/Zn-SOD activity was also found in another APP transgenic mouse model, in APP23 mice. In post mortem brain tissue from sporadic AD patients activities of Cu/Zn-SOD and GPx were however increased, and changes were most pronounced in temporal cortex. Simultaneously, levels of HNE but not MDA were elevated. Additionally, in vitro stimulation of lipid peroxidation led to increased MDA formation in samples from AD patients, indicating that increased activity of Cu/Zn-SOD and GPx are insufficient to protect against oxidative damage. Furthermore, the observed changes were subject to a gender effect, as samples from female AD patients showed increased activities of Cu/Zn-SOD and GPx as well as increased HNE levels, indicating that brain tissue from females is more sensitive towards oxidative damage. Levels of soluble Ab1-40 were positively correlated with with MDA levels and activities of Cu/Zn-SOD and GPx. Additionally, levels of lipid peroxidation products MDA and HNE are gene-dose-dependently modulated by the Apolipoprotein E4 allele, the most important genetic risk factor for AD known so far. While MDA levels were negatively correlated with MMSE scores, a measure for cognitive function, HNE levels were highest in AD patients with moderate cognitive impairment. Hence, increased HNE levels may play an important role in neurodegenerative events at an early disease stage. In summary, oxidative damage, as assessed by increased HNE levels, could be detected in sporadic AD patients and in different transgenic mouse models. The results of this thesis therefore support the further research of pharmacological targets aiming at augmentation of antioxidant defences for therapy or prophylaxis of Alzheimer’s disease.