scholarly journals Identifying Senescent Cells That Drive Aging

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 247-247
Author(s):  
Laura Niedernhofer
Keyword(s):  
Genotoxic Stress ◽  
Cell Types ◽  
Lead Target ◽  
Negative Consequences ◽  
Potent Inducer ◽  
Age Related ◽  
Specific Manner ◽  
Suppressor Mechanism ◽  
The Impact ◽  
Potent Tumor

Abstract Cellular senescence is a potent tumor suppressor mechanism. However, the untoward effect is that the accumulation of senescent cells promotes loss of resilience, aging and age-related diseases. One approach to maintaining the benefits of senescence while preventing the negative consequences is senolytic therapies: drugs that do not prevent senescence, but selectively kill senescent cells. Since virtually any type of cell can become senescent, it is important to identify the lineages of senescent cells that are most potent at driving loss of tissue homeostasis and aging. This will enable honing development of senolytics. We used a genetic approach to drive increased genotoxic stress, a potent inducer of senescence, in a tissue specific manner. The impact of this targeted senescence on different organs and cell types will be discussed, identifying a lead target for senolytics.

scholarly journals Thrombospondin-1 in maladaptive aging responses: a concept whose time has come

2020 ◽  
Vol 319 (1) ◽  
pp. C45-C63
Author(s):  
Jeffrey S. Isenberg ◽  
David D. Roberts
Keyword(s):  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Genotoxic Stress ◽  
Cell Types ◽  
Cellular Tissue ◽  
Therapeutic Agents ◽  
Age Related ◽  
Organ Systems ◽  
Age Dependent ◽  
Thrombospondin 1

Numerous age-dependent alterations at the molecular, cellular, tissue and organ systems levels underlie the pathophysiology of aging. Herein, the focus is upon the secreted protein thrombospondin-1 (TSP1) as a promoter of aging and age-related diseases. TSP1 has several physiological functions in youth, including promoting neural synapse formation, mediating responses to ischemic and genotoxic stress, minimizing hemorrhage, limiting angiogenesis, and supporting wound healing. These acute functions of TSP1 generally require only transient expression of the protein. However, accumulating basic and clinical data reinforce the view that chronic diseases of aging are associated with accumulation of TSP1 in the extracellular matrix, which is a significant maladaptive contributor to the aging process. Identification of the relevant cell types that chronically produce and respond to TSP1 and the molecular mechanisms that mediate the resulting maladaptive responses could direct the development of therapeutic agents to delay or revert age-associated maladies.

scholarly journals Integrative single-cell and bulk RNA-seq analysis in human retina identified cell type-specific composition and gene expression changes for age-related macular degeneration

2019 ◽  
Author(s):  
Yafei Lyu ◽  
Randy Zauhar ◽  
Nico Dana ◽  
Christianne E. Strang ◽  
Kui Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Macular Degeneration ◽  
Single Cell ◽  
Cell Types ◽  
Age Related Macular Degeneration ◽  
Peripheral Retina ◽  
Rna Seq ◽  
Cell Type ◽  
Age Related ◽  
The Impact

Age-related macular degeneration (AMD) preferentially affects distinct cell types and topographic regions in retina. To characterize the impact of AMD on gene expression changes across retinal cell types and regions, we generated both single-cell RNA-seq (scRNA-seq) and bulk RNA-seq data from macular and peripheral retina in postmortem human donors with and without AMD. The scRNA-seq data revealed 11 major cell types with many previously reported AMD risk genes showing substantial cell type and region specificity. Cell type proportional changes with advancing AMD stage were significant for Müller glia, rods, astrocytes, microglia and endothelium.

scholarly journals Expression of Exosome Biogenesis Genes is Pervasively Altered by Aging in the Mouse and in the Human Brain During Alzheimer's Disease

2021 ◽  
Author(s):  
Dan Lark ◽  
Thomas J LaRocca
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Types ◽  
Cell Populations ◽  
Cell Type ◽  
Body Protein ◽  
Common Gene ◽  
Exosome Biogenesis ◽  
Age Related ◽  
The Impact

Extracellular vesicles (EVs) like exosomes are secreted by numerous cell types in a variety of tissues. EVs have been implicated in both aging and age-related disorders like Alzheimer's disease (AD). However, how aging and AD affect EV biogenesis within and across cell types is poorly understood. Moreover, cells acquire characteristics based on tissue niche, but the impact of tissue residence on cell type EV biogenesis is unknown. We explored the Tabula Muris Senis, Mayo RNA-seq and ROSMAP data sets to characterize the cell and tissue-specific effects of aging and AD on genes involved in EV biogenesis. Specifically, we examined the age-dependent expression (age coefficient) of genes involved in EV biogenesis (22 genes), EV cargo (3 genes) and senescence (5 genes). Of the 131 cell populations (cell type x tissue) studied, 95 have at least one EV biogenesis gene impacted by age. The most common gene increased by age was charged multivesicular body protein 2A (CHMP2A) (54 cell populations). The most common gene decreased by age was syndecan binding protein (SDCBP) (58 cell populations). The senescence-associated genes cyclin-dependent kinase 1A (CDKN1A) and CDKN2A were not related to changes in CHMP2A and SDCBP and were altered by age in fewer cell populations. Finally, individuals with AD had decreased CHMP2A and increased SDCBP expression, opposite of what is observed with aging in the absence of diagnosed neurological disease. These findings indicate that age modifies exosome biogenesis gene expression in many cell populations mostly independent of senescence, and may be further altered in AD.

scholarly journals Wnt/β-Catenin Signaling Promotes Differentiation of Ischemia-Activated Adult Neural Stem/Progenitor Cells to Neuronal Precursors

2021 ◽  
Vol 15 ◽  
Author(s):  
Jan Kriska ◽  
Lucie Janeckova ◽  
Denisa Kirdajova ◽  
Pavel Honsa ◽  
Tomas Knotek ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Progenitor Cells ◽  
Wnt Pathway ◽  
Cultured Cells ◽  
Focal Cerebral Ischemia ◽  
Cell Types ◽  
Adult Brain ◽  
Negative Consequences ◽  
Neural Stem Progenitor Cells ◽  
The Impact

Modulating endogenous regenerative processes may represent a suitable treatment for central nervous system (CNS) injuries, such as stroke or trauma. Neural stem/progenitor cells (NS/PCs), which naturally reside in the subventricular zone (SVZ) of the adult brain, proliferate and differentiate to other cell types, and therefore may compensate the negative consequences of ischemic injury. The fate of NS/PCs in the developing brain is largely influenced by Wingless/Integrated (Wnt) signaling; however, its role in the differentiation of adult NS/PCs under ischemic conditions is still enigmatic. In our previous study, we identified the Wnt/β-catenin signaling pathway as a factor promoting neurogenesis at the expense of gliogenesis in neonatal mice. In this study, we used adult transgenic mice in order to assess the impact of the canonical Wnt pathway modulation (inhibition or hyper-activation) on NS/PCs derived from the SVZ, and combined it with the middle cerebral artery occlusion (MCAO) to disclose the effect of focal cerebral ischemia (FCI). Based on the electrophysiological properties of cultured cells, we first identified three cell types that represented in vitro differentiated NS/PCs – astrocytes, neuron-like cells, and precursor cells. Following FCI, we detected fewer neuron-like cells after Wnt signaling inhibition. Furthermore, the immunohistochemical analysis revealed an overall higher expression of cell-type-specific proteins after FCI, indicating increased proliferation and differentiation rates of NS/PCs in the SVZ. Remarkably, Wnt signaling hyper-activation increased the abundance of proliferating and neuron-like cells, while Wnt pathway inhibition had the opposite effect. Finally, the expression profiling at the single cell level revealed an increased proportion of neural stem cells and neuroblasts after FCI. These observations indicate that Wnt signaling enhances NS/PCs-based regeneration in the adult mouse brain following FCI, and supports neuronal differentiation in the SVZ.

scholarly journals Young people in the age of the COVID-19 pandemic: the age-related benefits and limitations

2021 ◽  
Vol 5 (2) ◽  
pp. 20-28
Author(s):  
Maiya A. Yadova
Keyword(s):  
Young People ◽  
Digital Literacy ◽  
Modern World ◽  
Sociological Research ◽  
Negative Consequences ◽  
Social Transformations ◽  
Generation Z ◽  
Age Related ◽  
Quality Health ◽  
The Impact

This article explores the prospects of the impact of the COVID-19 pandemic on young people in Russia and abroad. Particular attention is paid to the phenomenon that modern researchers refer to as “coronavirus ageism”. This study shows that in the age of the pandemic, the young age becomes a natural resource that significantly increases the chances of adapting to the social transformations caused by the pandemic. The author’s sociological research of adaptation strategies and social practices of the post-Soviet youth in the age of the pandemic shows that digital acumen helps to overcome the negative consequences of the coronavirus crisis. The mediation role of the first digital generations in the modern world — Millennials and Generation Z — is important in transferring IT knowledge and skills to older generations. Thus, the intensity of intergenerational contacts can be considered as one of the key factors positively influencing the digital literacy of older generations. This fact provides an opportunity to look differently at the familiar problem of the generational gap. However, there are deprived young people for whom the prospects of succeeding in life in the age of the new coronavirus pandemic are slim. Many young people living in the world’s poorest countries (or regions) have limited access to digital technologies and education. Some young people are cut off from quality health services, which poses a threat not only to their health but also to their lives. Some young people are faced with the hardships of unemployment, suffer from violence, cannot cope with negative emotions and loneliness, have experienced the death of loved ones or friends, etc.

scholarly journals Diminished satellite cells and elevated adipogenic gene expression in muscle as caused by ovariectomy are averted by low-magnitude mechanical signals

2015 ◽  
Vol 119 (1) ◽  
pp. 27-36 ◽  
Author(s):  
Danielle M. Frechette ◽  
Divya Krishnamoorthy ◽  
Benjamin J. Adler ◽  
M. Ete Chan ◽  
Clinton T. Rubin
Keyword(s):  
Gene Expression ◽  
Satellite Cell ◽  
Visceral Adiposity ◽  
Cell Populations ◽  
Negative Consequences ◽  
Mechanical Signals ◽  
Age Related ◽  
Adipogenic Gene ◽  
The Impact ◽  
Total P

Age-related degeneration of the musculoskeletal system, accelerated by menopause, is further complicated by increased systemic and muscular adiposity. The purpose of this study was to identify at the molecular, cellular, and tissue levels the impact of ovariectomy on adiposity and satellite cell populations in mice and whether mechanical signals could influence any outcomes. Eight-week-old C57BL/6 mice were ovariectomized, with one half subjected to low-intensity vibration (LIV; 0.3 g/90 Hz, 15 min/day, 5 day/wk; n = 10) for 6 wk and the others sham vibrated (OVX; n = 10). Data are compared with age-matched, intact controls (AC; n = 10). In vivo μCT analysis showed that OVX mice gained 43% total ( P < 0.001) and 125% visceral adiposity ( P < 0.001) compared with their baseline after 6 wk, whereas LIV gained only 21% total ( P = 0.01) and 70% visceral adiposity ( P < 0.01). Relative to AC, expression of adipogenic genes (PPARγ, FABP4, PPARδ, and FoxO1) was upregulated in OVX muscle ( P < 0.05), whereas LIV reduced these levels ( P < 0.05). Adipogenic gene expression was inversely related to the percentage of total and reserve satellite cell populations in the muscle, with both declining in OVX compared with AC (−21 and −28%, respectively, P < 0.01). LIV mitigated these declines (−11 and −17%, respectively). These results provide further evidence of the negative consequences of estrogen depletion and demonstrate that mechanical signals have the potential to interrupt subsequent adipogenic gene expression and satellite cell suppression, emphasizing the importance of physical signals in protecting musculoskeletal integrity and slowing the fat phenotype.

Conflicts in Biafra, Katanga and Cabinda as a result of the geopolitical legacy of colonialism

2020 ◽  
Vol 2020 (10-3) ◽  
pp. 238-246
Author(s):  
Olga Dzhenchakova
Keyword(s):  
Democratic Republic ◽  
Economic Factor ◽  
Colonial Period ◽  
Sub Saharan Africa ◽  
Negative Consequences ◽  
Post Colonial ◽  
Republic Of The Congo ◽  
Sub Saharan ◽  
The Republic ◽  
The Impact

The article considers the impact of the colonial past of some countries in sub-Saharan Africa and its effect on their development during the post-colonial period. The negative consequences of the geopolitical legacy of colonialism are shown on the example of three countries: Nigeria, the Democratic Republic of the Congo and the Republic of Angola, expressed in the emergence of conflicts in these countries based on ethno-cultural, religious and socio-economic contradictions. At the same time, the focus is made on the economic factor and the consequences of the consumer policy of the former metropolises pursuing their mercantile interests were mixed.

HOW CLIMATE CHANGE CAN INFLUENCE THE AGRICULTURE IN UKRAINE: A REVIEW

2020 ◽  
Author(s):  
N. Maidanovych ◽  
Keyword(s):  
Climate Change ◽  
Crop Yields ◽  
Soil Surface ◽  
Winter Period ◽  
Negative Consequences ◽  
Resource Saving ◽  
Impact Of Climate Change ◽  
Positive Effects ◽  
Average Annual Temperature ◽  
The Impact

The purpose of this work is to review and analyze the main results of modern research on the impact of climate change on the agro-sphere of Ukraine. Results. Analysis of research has shown that the effects of climate change on the agro-sphere are already being felt today and will continue in the future. The observed climate changes in recent decades have already significantly affected the shift in the northern direction of all agro-climatic zones of Europe, including Ukraine. From the point of view of productivity of the agro-sphere of Ukraine, climate change will have both positive and negative consequences. The positives include: improving the conditions of formation and reducing the harvesting time of crop yields; the possibility of effective introduction of late varieties (hybrids), which require more thermal resources; improving the conditions for overwintering crops; increase the efficiency of fertilizer application. Model estimates of the impact of climate change on wheat yields in Ukraine mainly indicate the positive effects of global warming on yields in the medium term, but with an increase in the average annual temperature by 2 ° C above normal, grain yields are expected to decrease. The negative consequences of the impact of climate change on the agrosphere include: increased drought during the growing season; acceleration of humus decomposition in soils; deterioration of soil moisture in the southern regions; deterioration of grain quality and failure to ensure full vernalization of grain; increase in the number of pests, the spread of pathogens of plants and weeds due to favorable conditions for their overwintering; increase in wind and water erosion of the soil caused by an increase in droughts and extreme rainfall; increasing risks of freezing of winter crops due to lack of stable snow cover. Conclusions. Resource-saving agricultural technologies are of particular importance in the context of climate change. They include technologies such as no-till, strip-till, ridge-till, which make it possible to partially store and accumulate mulch on the soil surface, reduce the speed of the surface layer of air and contribute to better preservation of moisture accumulated during the autumn-winter period. And in determining the most effective ways and mechanisms to reduce weather risks for Ukrainian farmers, it is necessary to take into account the world practice of climate-smart technologies.

Financial Risks of the Bank: Assessment and Mechanism of Neutralization

2020 ◽  
Vol 22 (1) ◽  
pp. 6-12
Author(s):  
Nelia Volkova ◽  
◽  
Alina Mukhina ◽  
Keyword(s):  
Risk Assessment ◽  
Financial Stability ◽  
Financial Risk ◽  
Stable Operation ◽  
Financial Risks ◽  
Negative Consequences ◽  
Conceptual Approach ◽  
Relevant Today ◽  
Banking Institution ◽  
The Impact

Abstract. Introduction. The issue of financial risk management of commercial banks is quite relevant today, because the activity of banks is the most risky of all. The presence of risks in banking can lead to unexpected losses, namely the loss of own resources. That’s why for the stable operation of the bank without loss the priority is to assess the financial risks, which is the basis for their further neutralization. Purpose. The purpose of the article is to develop conceptual provisions for assessment financial risks and justifying the need to neutralize them. Results. The article analyzes the impact of risks on the financial stability of a banking institution. The main methods of bank risk assessment are considered. All these include the statistical method, the analytical method, the expert method, the analogue method and the combined method. The necessity of neutralization of financial risks in order to avoid negative consequences is substantiated. Also the methods of bank risks neutralization are considered. It should be noted that these methods of neutralization can not only be used, but also supplement the list with new methods must be done, which in the future will protect the bank from the influence of undesirable factors. A conceptual approach to the assessment and neutralization of financial risks is proposed. This conceptual approach aims to ensure effective assessment of the level of risk with their subsequent neutralization Conclusions. Use of a conceptual approach will allow an effective risk assessment and decision-making to avoid or accept risk. Thanks to using this approach, the banking institution will be able to react swiftly to the presence of financial risks and to prevent the occurrence of negative consequences, which may lead to a violation of the financial stability of the bank.

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