Suchergebnisse

Abstract
Inhaled air pollutants (AirP) comprise extraordinarily diverse particles, volatiles, and gases from traffic, wildfire, cigarette smoke, dust, and various other sources. These pollutants contain numerous toxic components, which collectively differ in relative levels of components, but broadly share chemical classes. Exposure and health outcomes from AirP are complex, depending on pollutant source, duration of exposure, and socioeconomic status. We discuss examples in the current literature on organ responses to AirP, with a focus on lung, arteries, and brain. Some transcriptional responses are shared. It is well accepted that AirP contributes to Alzheimer's disease and other neurodegenerative conditions in the Gero-Exposome. However, we do not know which chemical compounds initiate these changes and how activation of these transcriptional pathways is further modified by genetics and prenatal development.

Abstract
Epigenetic changes have been established to be a hallmark of aging, which implies that aging science requires collaborating with the field of chromatin biology. DNA methylation patterns, changes in relative abundance of histone post-translational modifications, and chromatin remodeling are the central players in modifying chromatin structure. Aging is commonly associated with an overall increase in chromatin instability, loss of homeostasis, and decondensation. However, numerous publications have highlighted that the link between aging and chromatin changes is not nearly as linear as previously expected. This complex interplay of these epigenetic elements during the lifetime of an organism likely contributes to cellular senescence, genomic instability, and disease susceptibility. Yet, the causal links between these phenomena still need to be fully unraveled. In this perspective article, we discuss potential future directions of aging chromatin biology.

Context: SMEs represent approximately 50% of world GDP and due to the Covid-19 pandemic, they have been severely affected. This document provides an overview of the factors that affected the economy of SMEs and presents some solutions to maintain their operation in times of difficulties. Methodology: The elaboration of the manuscript is supported in relevant literature published between 2019-2021. The search strategy was applied through the databases EMBASE, WEB OF SCIENCES, SCOPUS under key search terms COVID-19, pandemic, small enterprises, medium-sized enterprises, global economic, economic growth, developing countries, emerging economies, economic impact, financial fragility, government action*, credit risk, travel restriction*, e-commerce, digital technologie*, digital transformation, emerging market*, supply chain*, small business. Subsequently, the document classification and analysis were carried out through the Raceer method (compilation, storage, conceptual schematic elaboration, link of informative units, writing). Results: The analysis of the relevant information revealed that the economy of SMEs played an important role in the sharp drop in GDP and in the increase in poverty and unemployment levels worldwide, and that those that wanted to remain in operation, they had to reinvent themselves and dabble in new business strategies. Conclusions: The pandemic generated by Covid-19 produced significant changes in purchasing habits, manufacturing methods and ways of working that seriously impacted the performance of SMEs. To deal with this new economic scenario, technology and innovation are expected to lead to new rapidly adapting business models. ; Contexto: Las pymes representan aproximadamente el 50 % del PIB mundial, y debido a la pandemia por la covid-19, se han visto gravemente afectadas. Este documento proporciona un panorama general de factores que incidieron en la economía de las pymes y presenta algunas soluciones para mantener su operación en tiempos de dificultades. Metodología: La elaboración ...

Abstract
The biological aging of stem cells (exhaustion) is proposed to contribute to the development of a variety of age-related conditions. Despite this, little is understood about the specific mechanisms which drive this process. In this study, we assess the transcriptomic and proteomic changes in three different populations of mesenchymal progenitor cells from older (50-70 years) and younger (20-40 years) individuals to uncover potential mechanisms driving stem cell exhaustion in mesenchymal tissues. To do this, we harvested primary bone marrow mesenchymal stem and progenitor cells (MPCs), circulating osteoprogenitors (COP), and adipose-derived stem cells (ADSCs) from younger and older donors, with an equal number of samples from males and females. These samples underwent RNA sequencing and label-free proteomic analysis, comparing the younger samples to the older ones. There was a distinct transcriptomic phenotype in the analysis of pooled older stem cells, suggestive of suppressed proliferation and differentiation; however, these changes were not reflected in the proteome of the cells. Analyzed independently, older MPCs had a distinct phenotype in both the transcriptome and proteome consistent with altered differentiation and proliferation with a pro-inflammatory immune shift in older adults. COP cells showed a transcriptomic shift to pro-inflammatory signaling but no consistent proteomic phenotype. Similarly, ADSCs displayed transcriptomic shifts in physiologies associated with cell migration, adherence, and immune activation but no proteomic change with age. These results show that there are underlying transcriptomic changes with stem cell aging that may contribute to a decline in tissue regeneration. However, the proteome of the cells was inconsistently regulated.

Abstract
In the brain, environmental changes, such as neuroinflammation, can induce senescence, characterized by the decreased proliferation of neurons and dendrites and synaptic and vascular damage, resulting in cognitive decline. Senescence promotes neuroinflammatory disorders by senescence-associated secretory phenotypes and reactive oxygen species. In human brain microvascular endothelial cells (HBMVECs), we demonstrate that chronological aging and irradiation increase death-associated protein kinase 3 (DAPK3) expression. To confirm the role of DAPK3 in HBMVEC senescence, we disrupted DAPK3 activity using small interfering RNA (siRNA) or a dominant-negative mutant (DAPK3-P216S), which reduced cellular senescence phenotypes, as assessed by changes in tube formation, senescence-associated beta-galactosidase activity, and cell proliferation. In endothelial cells, DAPK3 promotes cellular senescence by regulating the phosphorylation and inactivation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) via the protein kinase B pathway, resulting in the decreased expression of mitochondrial metabolism-associated genes, such as ATP5G1, BDNF, and COX5A. Our studies show that DAPK3 is involved in cellular senescence and PGC1α regulation, suggesting that DAPK3 regulation may be important for treating aging-related brain diseases or the response to radiation therapy.

Abstract
The National Institute on Aging sponsored a symposium at the Gerontological Society of America (GSA) annual meeting in Indianapolis, Indiana, to discuss recent discoveries related to senescent and inflammatory mechanisms in aging and disease. Consistent with the 2022 Biological Sciences GSA program led by Dr. Rozalyn Anderson, the symposium featured early-stage investigators and a leader in the field of geroscience research. Cell senescence and immune interactions coordinate homeostatic and protective programming throughout the life span. Dysfunctional communication in this exchange eventuates in inflammation-related compositional changes in aged tissues, including propagation of the senescence-associated secretory phenotype and accumulation of senescent and exhausted immune cells. Presentations in this symposium explored senescent and immune-related dysfunction in aging from diverse viewpoints and featured emerging cellular and molecular methods. A central takeaway from the event was that the use of new models and approaches, including single-cell -omics, novel mouse models, and 3D culture systems, is revealing dynamic properties and interactions of senescent and immune cell fates. This knowledge is critical for devising new therapeutic approaches with important translational relevance.

Issue addressed: Exercising outdoors provide beneficial effect on mental and physical health for all ages. However, few older people exercise outdoors other than walking. While outdoor gyms have become increasingly common in Australia, limited outdoor exercise equipment specifically designed for older people is available in public spaces. We have set up and evaluated a unique purpose-built outdoor exercise park for older people in the community setting and demonstrated positive physical and well-being outcomes associated with the provision of this unique exercise mode and social programme. Methods: This study is a reflective narrative describing this innovative exercise approach and reports challenges associated with establishment of the exercise park, conducting the randomised trial, strategies adopted to address these challenges and recommendations for future implementation of this approach in the community. Results: Many challenges were encountered, including securing appropriate land to locate the exercise park, control of environmental factors for safety (non-slippery ground and equipment) as well as logistics in running the exercise programme itself. Several adjustments in the equipment were also required to ensure safe use by older people. Conclusion: The inclusion of outdoor equipment for older people in public spaces or urban parks is important and careful consideration needs to be taken by local/public authorities to provide access, amenities and safety for all as well as activities to suit all ages. So what?: Seniors' exercise parks can be installed in public places and may provide an enjoyable and effective approach to engage older individuals in a more active and healthier lifestyle.

BACKGROUND: The physical environment has been shown to have a positive effect on the promotion of physical activity of older people. Outdoor environments that incorporate specialised exercise equipment suitable for older people are uniquely placed to promote physical activity and social connectedness amongst older people. The ENJOY project included the installation of specialised outdoor exercise equipment (the Seniors Exercise Park) and the delivery of a physical and social activity program for older people as part of a prospective pre-post research design. The installation of the specialised equipment in public sites and an aged care facility was also aimed at increasing usage of the equipment by older people from the wider community and to increase physical and social activities. METHOD: A conceptual framework for implementation and several engagement methods were utilised to guide the research and to support the participating partners throughout the project. This paper is a reflective narrative describing the collaborative process and approach utilised to engage local governments and community, and reports the challenges and the lessons learnt to inform future strategies for implementation. RESULTS: The conceptual framework for the implementation process that guided the conduct and delivery of the ENJOY project included the core elements of the Interactive Systems Framework and the ecologic framework. These models incorporate elements of research-to-practice and community-centred implementation to accommodate the unique perspectives of a range of stakeholders. CONCLUSION: Partner characteristics such as local governments' structure and policy as well as community factors can impact on implementation. Partnership with local governments with effective communication, strategic planning and community and seniors engagement approaches are recommended for successful implementation. The lessons learnt can further assist public health research design around changes to the built environment to positively impact on ...

Background: The physical environment has been shown to have a positive effect on the promotion of physical activity of older people. Outdoor environments that incorporate specialised exercise equipment suitable for older people are uniquely placed to promote physical activity and social connectedness amongst older people. The ENJOY project included the installation of specialised outdoor exercise equipment (the Seniors Exercise Park) and the delivery of a physical and social activity program for older people as part of a prospective pre-post research design. The installation of the specialised equipment in public sites and an aged care facility was also aimed at increasing usage of the equipment by older people from the wider community and to increase physical and social activities. Method: A conceptual framework for implementation and several engagement methods were utilised to guide the research and to support the participating partners throughout the project. This paper is a reflective narrative describing the collaborative process and approach utilised to engage local governments and community, and reports the challenges and the lessons learnt to inform future strategies for implementation. Results: The conceptual framework for the implementation process that guided the conduct and delivery of the ENJOY project included the core elements of the Interactive Systems Framework and the ecologic framework. These models incorporate elements of research-to-practice and community-centred implementation to accommodate the unique perspectives of a range of stakeholders. Conclusion: Partner characteristics such as local governments' structure and policy as well as community factors can impact on implementation. Partnership with local governments with effective communication, strategic planning and community and seniors engagement approaches are recommended for successful implementation. The lessons learnt can further assist public health research design around changes to the built environment to positively impact on older people's physical activity levels.

Background: Creating inclusive and accessible outdoor environments that provide and encourage opportunities for older adults to engage in physical activity and social interaction is important for healthy ageing. The Senior Exercise Park is outdoor exercise equipment designed specifically for use by older people that provides physical and social benefits for older people in the community, and has the potential to be used widely as a sustainable mode of physical activity. The aim of this study is to implement and evaluate the effects of sustained engagement through the use of a community-based novel outdoor physical activity program (purpose-built exercise park) for older people on physical, mental and social health and physical activity outcomes (the ENJOY project). Methods: This is a prospective pre-post design study with 12 months follow up. Adults aged ≥60 years will be recruited from the general community from the suburbs close to the Senior Exercise Parks locations in Melbourne. Participants will undergo a 12 week structured supervised physical activity program using the outdoor Senior Exercise Park equipment followed by 6 months unstructured physical activity program. Participants will be assessed at baseline, 3, 9, and 12 months. The following outcomes will be assessed: physical activity, physical function, psychosocial and mental health outcomes, falls risk and falls occurrence, participants' feedback and satisfaction, and health care resource use. Discussion: The ENJOY trial is designed to operate in a community setting with local government engagement to maximise the usage of the exercise park and provide an outdoor space for older people to be physically active. This project will evaluate the effectiveness and sustainability of the outdoor exercise park on a range of health outcomes and its long-term usability in the community. Trial registration: This trial is prospectively registered with the Australian New Zealand Clinical Trials Registry. Trial registration number ACTRN12618001727235 registered 18th of October 2018.

Background: Creating inclusive and accessible outdoor environments that provide and encourage opportunities for older adults to engage in physical activity and social interaction is important for healthy ageing. The Senior Exercise Park is outdoor exercise equipment designed specifically for use by older people that provides physical and social benefits for older people in the community, and has the potential to be used widely as a sustainable mode of physical activity. The aim of this study is to implement and evaluate the effects of sustained engagement through the use of a community-based novel outdoor physical activity program (purpose-built exercise park) for older people on physical, mental and social health and physical activity outcomes (the ENJOY project). Methods: This is a prospective pre-post design study with 12 months follow up. Adults aged ≥60 years will be recruited from the general community from the suburbs close to the Senior Exercise Parks locations in Melbourne. Participants will undergo a 12 week structured supervised physical activity program using the outdoor Senior Exercise Park equipment followed by 6 months unstructured physical activity program. Participants will be assessed at baseline, 3, 9, and 12 months. The following outcomes will be assessed: physical activity, physical function, psychosocial and mental health outcomes, falls risk and falls occurrence, participants' feedback and satisfaction, and health care resource use. Discussion: The ENJOY trial is designed to operate in a community setting with local government engagement to maximise the usage of the exercise park and provide an outdoor space for older people to be physically active. This project will evaluate the effectiveness and sustainability of the outdoor exercise park on a range of health outcomes and its long-term usability in the community. Trial registration: This trial is prospectively registered with the Australian New Zealand Clinical Trials Registry. Trial registration number ACTRN12618001727235 registered ...

Abstract
Kidney aging accelerates the progression of various acute and chronic kidney diseases and can also induce pathological changes in other organs throughout the body. Circular RNAs (circRNAs) have been demonstrated to play a vital role in aging and age-related diseases. However, biological functions and the underlying molecular mechanism of circRNAs in kidney aging remain largely unclear. Uncovering the functions of circRNAs in kidney aging and their underlying regulatory mechanisms may shed new light on the development of novel diagnostic and therapeutic strategies for human aging. Here, we report the important role of circVmn2r1 in the progression of kidney aging. We found that circVmn2r1 was one of the top expressed circRNAs in mouse kidney by RNA sequencing and was significantly upregulated in 24-month-old mouse kidney compared to 3-month-old. More importantly, we demonstrated that overexpression of circVmn2r1 promoted kidney aging in senescence-accelerated mouse prone 8 mice. Cellular assays with mouse kidney tubular epithelium (TCMK-1) cells under both gain-of-function and loss-of-function conditions demonstrated that circVmn2r1 inhibited proliferation and promoted senescence, whereas miR-223-3p counteracted these effects. Mechanistic analysis demonstrated that circVmn2r1 acted as a miR-223-3p sponge to relieve the repressive effect of miR-223-3p on its target NLRP3, which we proved could inhibit proliferation and promote senescence of TCMK-1 cells. Our results indicate that circVmn2r1 promotes kidney aging through acting as a miR-223-3p sponge, consequently upregulating NLRP3 expression, and can be a valuable diagnostic marker and an important therapeutic target for kidney aging.

Abstract
Blood-based mitochondrial bioenergetic profiling is a feasible, economical, and minimally invasive approach that can be used to examine mitochondrial function and energy metabolism in human subjects. In this study, we use 2 complementary respirometric techniques to evaluate mitochondrial bioenergetics in both intact and permeabilized peripheral blood mononuclear cells (PBMCs) and platelets to examine sex dimorphism in mitochondrial function among older adults. Employing equal numbers of PBMCs and platelets to assess mitochondrial bioenergetics, we observe significantly higher respiration rates in female compared to male participants. Mitochondrial bioenergetic differences remain significant after controlling for independent parameters including demographic parameters (age, years of education), and cognitive parameters (mPACC5, COGDX). Our study illustrates that circulating blood cells, immune cells in particular, have distinctly different mitochondrial bioenergetic profiles between females and males. These differences should be taken into account as blood-based bioenergetic profiling is now commonly used to understand the role of mitochondrial bioenergetics in human health and aging.

Abstract
High engagement in lifestyle health behaviors appears to be protective against cognitive decline in aging. We investigated the association between patterns of modifiable lifestyle health behaviors and common brain neuropathologies of dementia as a possible mechanism. We examined 555 decedents from the Rush Memory and Aging Project, free of dementia at their initial concurrent report of lifestyle health behaviors of interest (physical, social, and cognitive activities, and healthy diet), and who underwent a postmortem neuropathology evaluation. First, we used latent profile analysis to group participants based on baseline behavior patterns. Second, we assessed the associations of profile membership with each neurodegenerative (global Alzheimer's disease [AD] pathology, amyloid-beta load, density of neurofibrillary tangles, and presence of cortical Lewy bodies and TAR DNA-binding protein 43 cytoplasmic inclusions) and neurovascular pathologies (presence of chronic gross or microscopic infarcts, arteriolosclerosis, atherosclerosis, and cerebral amyloid angiopathy), using separate linear or logistic regression models, adjusted for age at death, sex (core model), vascular disease risk factors, and vascular conditions (fully adjusted model). Participants had either consistently lower (N = 224) or consistently higher (N = 331) engagement across 4 lifestyle health behaviors. We generally found no differences in neuropathologies between higher and lower engagement groups in core or fully adjusted models; for example, higher engagement in lifestyle health behaviors was not associated with global AD pathology after core or full adjustment (both p > .8). In conclusion, we found no evidence of associations between patterns of lifestyle health behaviors and neuropathology. Other mechanisms may underlie protective effects of health behaviors against dementia.