scholarly journals Age-Dependent Protective Effect of Selenium against UVA Irradiation in Primary Human Keratinocytes and the Associated DNA Repair Signature

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
C. Favrot ◽  
D. Beal ◽  
E. Blouin ◽  
M. T. Leccia ◽  
A. M. Roussel ◽  
...  

Few studies have focused on the protective role of selenium (Se) against skin aging and photoaging even though selenoproteins are essential for keratinocyte function and skin development. To the best of our knowledge, the impact of Se supplementation on skin cells from elderly and young donors has not been reported. Therefore, the main objective of our study was to evaluate the effects of Se supplementation on skin keratinocytes at baseline and after exposure to ultraviolet A (UVA) irradiation. Low doses of Se (30 nM) were very potently protective against UVA-induced cytotoxicity in young keratinocytes, whereas the protection efficiency of Se in old keratinocytes required higher concentrations (240 nM). Additionally, the DNA repair ability of the old keratinocytes drastically decreased compared with that of the young keratinocytes at baseline and after the UVA exposure. The Se supplementation significantly enhanced the DNA repair of 8-oxoguanine (8oxoG) only in the keratinocytes isolated from young donors. Therefore, aged keratinocytes have an increased vulnerability to oxidative DNA damage, and the Se needs in the elderly should be considered. Strengthening DNA repair activities with Se supplementation may represent a new strategy to combat aging and skin photoaging.

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Lavinia Tinaburri ◽  
Mariarosaria D’Errico ◽  
Sara Sileno ◽  
Riccardo Maurelli ◽  
Paolo Degan ◽  
...  

Oxidative DNA damage accumulation may induce cellular senescence. Notably, senescent cells accumulate in aged tissues and are present at the sites of age-related pathologies. Although the signaling of DNA strand breaks has been extensively studied, the role of oxidative base lesions has not fully investigated in primary human keratinocyte aging. In this study, we show that primary human keratinocytes from elderly donors are characterized by a significant accumulation of the oxidative base lesion 8-OH-dG, impairment of oxidative DNA repair, and increase of miR-200a levels. Notably, OGG1-2a, a critical enzyme for 8-OH-dG repair, is a direct target of miR-200a and its expression levels significantly decrease in aged keratinocytes. The 8-OH-dG accumulation displays a significant linear relationship with the aging biomarker p16 expression during keratinocyte senescence. Interestingly, we found that miR-200a overexpression down-modulates its putative target Bmi-1, a well-known p16 repressor, and up-regulates p16 itself. miR-200a overexpression also up-regulates the NLRP3 inflammasome and IL-1β expression. Of note, primary keratinocytes from elderly donors are characterized by NRPL3 activation and IL-1β secretion. These findings point to miR-200a as key player in primary human keratinocyte aging since it is able to reduce oxidative DNA repair activity and may induce several senescence features through p16 and IL-1β up-regulation.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Maria P. Lambros ◽  
Lavanya Kondapalli ◽  
Cyrus Parsa ◽  
Hari Chandana Mulamalla ◽  
Robert Orlando ◽  
...  

Qingre Liyan decoction (QYD), a Traditional Chinese medicine, and N-acetyl cysteine (NAC) have been used to prevent radiation induced mucositis. This work evaluates the protective mechanisms of QYD, NAC, and their combination (NAC-QYD) at the cellular and transcriptional level. A validated organotypic model of oral mucosal consisting of a three-dimensional (3D) cell tissue-culture of primary human keratinocytes exposed to X-ray irradiation was used. Six hours after the irradiation, the tissues were evaluated by hematoxylin and eosin (H and E) and a TUNEL assay to assess histopathology and apoptosis, respectively. Total RNA was extracted and used for microarray gene expression profiling. The tissue-cultures treated with NAC-QYD preserved their integrity and showed no apoptosis. Microarray results revealed that the NAC-QYD caused the upregulation of genes encoding metallothioneins,HMOX1, and other components of the Nrf2 pathway, which protects against oxidative stress. DNA repair genes (XCP,GADD45G,RAD9, andXRCC1), protective genes (EGFRandPPARD), and genes of the NFκB pathway were upregulated. Finally, tissue-cultures treated prophylactically with NAC-QYD showed significant downregulation of apoptosis, cytokines and chemokines genes, and constrained damage-associated molecular patterns (DAMPs). NAC-QYD treatment involves the protective effect of Nrf2, NFκB, and DNA repair factors.


Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 344
Author(s):  
Silvia Cocchio ◽  
Tolinda Gallo ◽  
Stefania Del Zotto ◽  
Elena Clagnan ◽  
Andrea Iob ◽  
...  

Influenza and its complications are an important public health concern, and vaccination remains the most effective prevention measure. However, the efficacy of vaccination depends on several variables, including the type of strategy adopted. The goal of this study was to assess the impact of different influenza vaccination strategies in preventing hospitalizations for influenza and its related respiratory complications. A retrospective cohort study was conducted on data routinely collected by the health services for six consecutive influenza seasons, considering the population aged 65 years or more at the time of their vaccination and living in northeastern Italy. Our analysis concerns 987,266 individuals vaccinated against influenza during the study period. The sample was a mean 78.0 ± 7.7 years old, and 5681 individuals (0.58%) were hospitalized for potentially influenza-related reasons. The hospitalization rate tended to increase over the years, not-significantly peaking in the 2016–2017 flu season (0.8%). Our main findings revealed that hospitalizations related to seasonal respiratory diseases were reduced as the use of the enhanced vaccine increased (R2 = 0.5234; p < 0.001). Multivariate analysis confirmed the significantly greater protective role of the enhanced vaccine over the conventional vaccination strategy, with adjusted Odds Ratio (adj OR) = 0.62 (95% CI: 0.59–0.66). A prior flu vaccination also had a protective role (adj OR: 0.752 (95% CI: 0.70–0.81)). Age, male sex, and H3N2 mismatch were directly associated with a higher risk of hospitalization for pneumonia. In the second part of our analysis, comparing MF59-adjuvanted trivalent inactivated vaccine (MF59-TIV) with conventional vaccines, we considered 479,397 individuals, of which 3176 (0.66%) were admitted to a hospital. The results show that using the former vaccine reduced the risk of hospitalization by 33% (adj OR: 0.67 (95% CI: 0.59–0.75)). This study contributes to the body of evidence of a greater efficacy of enhanced vaccines, and MF59-adjuvanted TIV in particular, over conventional vaccination strategies in the elderly.


2009 ◽  
Vol 1187 ◽  
Author(s):  
Petra J. Kluger ◽  
Marc Panas ◽  
Lena Schober ◽  
Guenter E. M. Tovar ◽  
Heike Mertsching ◽  
...  

AbstractTo gain basic insight into the impact of non-biological features on cells’ behaviour, primary skin-cells, keratinocytes and fibroblasts, were cultured on amine-functionalized or carboxy-functionalized planar, nano- or microstructured surfaces. Sintered layers of silica nano- or microparticles were used to fabricate structures in the range of naturally occurring structure-sizes. Organo-chemical functionalization was achieved using organo-functional silanes. Primary human keratinocytes and fibroblasts were isolated from human foreskin and cultivated on the modified interfaces. Both cell-types displayed specific proliferation behaviour, depending on surface topography and chemical functionalization: Keratinocytes showed significantly better proliferation on amino-functionalized surfaces than on carboxy-functionalized surfaces. On amino-functional surfaces decree-topography. Fibroblasts, in contrast, tended to proliferate stronger on carboxylated surfaces. Immunohistological staining proofed that actin and vinculin, which is involved in the formation of focal adhesions, were expressed on all modified surfaces, thus revealing intact cytoskeleton and cell-substrate contacts.


2019 ◽  
Vol 20 (17) ◽  
pp. 4070 ◽  
Author(s):  
Matthew G. Brewer ◽  
Takeshi Yoshida ◽  
Fiona I. Kuo ◽  
Sade Fridy ◽  
Lisa A. Beck ◽  
...  

Atopic dermatitis (AD) is the most common chronic and relapsing inflammatory skin disease. AD is typically characterized by skewed T helper (Th) 2 inflammation, yet other inflammatory profiles (Th1, Th17, Th22) have been observed in human patients. How cytokines from these different Th subsets impact barrier function in this disease is not well understood. As such, we investigated the impact of the canonical Th17 cytokine, IL-17A, on barrier function and protein composition in primary human keratinocytes and human skin explants. These studies demonstrated that IL-17A enhanced tight junction formation and function in both systems, with a dependence on STAT3 signaling. Importantly, the Th2 cytokine, IL-4 inhibited the barrier-enhancing effect of IL-17A treatment. These observations propose that IL-17A helps to restore skin barrier function, but this action is antagonized by Th2 cytokines. This suggests that restoration of IL-17/IL-4 ratio in the skin of AD patients may improve barrier function and in so doing improve disease severity.


2021 ◽  
Author(s):  
Megha Jhanji ◽  
Chintada Nageswara Rao ◽  
Xueyan Zhou ◽  
C Keene ◽  
Tao Ma ◽  
...  

Abstract Human aging and neurodegenerative diseases accumulate oxidative DNA damage-associated mutations in neurons. Circadian-regulated tyrosine (Tyr) is increased during aging and in Alzheimer’s Disease (AD). Tyr exacerbates the cognitive decline in the elderly and AD patients. Tyrosyl-tRNA synthetase (TyrRS) that activates Tyr for protein synthesis and participates in DNA repair is depleted in the affected brain regions of AD patients through an unknown mechanism. Here, we found that increased Tyr levels decrease the nuclear and neurite levels of TyrRS in neurons and cause oxidative DNA damage. Although Tyr inhibits protein synthesis at the elongation step, dopamine (DA)- a neurotransmitter derived from Tyr increases TyrRS levels. We previously showed that Tyr inhibits TyrRS-mediated activation of poly-ADP-ribose polymerase 1 (PARP1), a modulator of DNA repair. We now found that trans-resveratrol (trans-RSV) that binds to TyrRS mimicking ‘Tyr conformation’ decreases TyrRS, inhibits DNA repair and induces neurotoxicity. Conversely, cis-RSV binds to TyrRS mimicking a ‘Tyr-free conformation,’ increases TyrRS, facilitates DNA repair, and protects neurons against multiple neurotoxic agents in a TyrRS-dependent manner. Our results suggest that increased Tyr levels may have causal effects in human aging and neurocognitive disorders and offer a plausible explanation to divergent results obtained in clinical trials using RSV.


2020 ◽  
Vol 18 (3) ◽  
pp. 221-228
Author(s):  
Piotr Czarnecki ◽  
◽  
Justyna Podgórska-Bednarz ◽  
Lidia Perenc ◽  
◽  
...  

Introduction. Physical activity is known to be an important factor influencing health throughout human life. This issue has become crucial for public health due to the aging of the population in both developed and developing countries. Aim. is to present a literature review on the forms of physical activity undertaken by the elderly, as well as on issues related to physical activity and the population aging. Material and methods. The study was prepared on the basis of a review of Polish and foreign literature. The following databases and data sources were used: EBSCO, ScienceDirect and Google Scholar. An additional source of data were the websites of the Central Statistical Office. Strictly defined key phrases were used during the collection of literature. The work has been divided into thematic subsections on the aging of the society, the impact of physical activity on health and the main topic, i.e. forms of physical activity selected by the elderly. Analysis of the literature. The number of elderly people in Polish society has increased by almost 3.7 million over three decades. Therefore, an important topic is prophylaxis aimed at increasing the number of days in good health, largely covering the broadly understood activation of the elderly. The available data indicate that only 12% of elderly people undertake physical activity once a week. The most common form of spending free time actively is walking (as many as 73% of people in this population declare this form of physical activity in one of the presented studies). Conclusion. Organized forms of physical activity are undertaken much less frequently by the analyzed age group mainly due to financial limitations and limited availability of sports infrastructure.


2004 ◽  
Vol 79 (3) ◽  
pp. 286 ◽  
Author(s):  
Marjorie Chazal ◽  
Emeric Roux ◽  
Claire Alapetite ◽  
Christophe Roulin ◽  
Ethel Moustacchi ◽  
...  

2017 ◽  
Vol 2 (1) ◽  
pp. 1
Author(s):  
Amirul Amin Ismail ◽  
Ismail Samsuddin ◽  
Azman Zainonabidin ◽  
Harlina Mohd Ali

By the year 2030, Malaysian population will experience the after effects of the rapid growth of ageing society. This paper investigates the impact of seamless integration of horticultural activity in the new residential typology of retirement community. It is believed that horticultural therapy is not only beneficial for physical and psychological but also promotes socialisation opportunities among the elderly. Comparative analysis method on selected precedent studies has been carried out and analysed in accordance with Malaysian context. Initial findings indicate that a retirement community with horticultural activity gives therapy for healthier well-being. This therapeutic activity can be apositive change in elderly lifestyle and essential towards the establishment of retirement community in Malaysia. 


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