Publications by authors named "Richard Siow"

Neutrophil extracellular traps (NETs) are large structures composed of chromatin, histones and granule-derived proteins released extracellularly by neutrophils. They are generally considered to be a part of the antimicrobial defense strategy, preventing the dissemination of pathogens. However, overproduction of NETs or their ineffective clearance can drive various pathologies, many of which are associated with advanced age and involve uncontrolled inflammation, oxidative, cardiovascular and neurodegenerative stress as underlying mechanisms.

View Article and Find Full Text PDF

Background: Dementia poses a significant global health challenge. Anthocyanins neutralize free radicals, modulate signaling pathways, inhibit pro-inflammatory genes, and suppress cytokine production and may thus have positive cognitive effects in people at increased risk of dementia. We aim to investigate the effects of purified anthocyanins on cognitive function in people at increased risk of dementia according to their inflammation status based on blood-based inflammatory biomarkers.

View Article and Find Full Text PDF

DailyColors™ is a supplement made up of several phytonutrients that aims to replicate elements from the Mediterranean diet. These include fruit, berry and vegetable extracts that are rich in key phytochemicals such as Quercetin, Catechins, Phloretin, Ellagic Acid, and Anthocyanins. Here, we determined the effects of DailyColors™ on the blood biomarkers associated with the diverse mechanisms implicated in ageing and age-related diseases, including mitochondrial function, inflammation, and oxidative stress, as well as on saliva's DNA methylation pattern.

View Article and Find Full Text PDF
Article Synopsis
  • * They discovered important signs of ageing and how they work together, which could help find ways to slow down or even reverse age-related diseases.
  • * A special meeting called the Longevity Med Summit in May 2023 brought experts together to talk about how to improve our health as we get older and live healthier lives for more years.
View Article and Find Full Text PDF
Article Synopsis
  • Recent studies show that zinc (Zn) is crucial for cardiovascular health, playing a role in protecting blood vessel lining from oxidative stress and regulating nitric oxide synthase.
  • Too much zinc can cause cell death in endothelial cells due to imbalances in antioxidant systems, while zinc deficiency leads to inflammation and heightened adhesion of immune cells.
  • The transcription factor NRF2 is activated by zinc, influencing numerous cellular processes including metabolism, repair, and response to oxidative stress, indicating that zinc levels may be a potential marker for diagnosing and treating related diseases.
View Article and Find Full Text PDF

Unhealthy aging poses a global challenge with profound healthcare and socioeconomic implications. Slowing down the aging process offers a promising approach to reduce the burden of a number of age-related diseases, such as dementia, and promoting healthy longevity in the old population. In response to the challenge of the aging population and with a view to the future, Norway and the United Kingdom are fostering collaborations, supported by a "Money Follows Cooperation agreement" between the 2 nations.

View Article and Find Full Text PDF
Article Synopsis
  • Sexually active older adults (ages 60-89) are increasingly vulnerable to HIV and other sexually transmitted infections (STIs) due to health issues and low condom usage; a study aimed to analyze these trends globally from 1990 to 2019.
  • The research collected data on HIV and various STIs from the Global Burden of Diseases Study across 204 countries, assessing incidence rates and disability-adjusted life-years (DALYs) to understand the impact on older populations.
  • Findings revealed that in 2019, there were approximately 77,000 new HIV cases and over 26 million new cases of other STIs among older adults, with a slight annual decline in HIV rates, while other STIs showed stable
View Article and Find Full Text PDF

Use of autologous cells isolated from elderly patients with multiple comorbidities may account for the modest efficacy of cell therapy in patients with chronic limb threatening ischemia (CLTI). We aimed to determine whether proarteriogenic monocyte/macrophages (Mo/MΦs) from patients with CLTI were functionally impaired and to demonstrate the mechanisms related to any impairment. Proarteriogenic Mo/MΦs isolated from patients with CLTI were found to have an impaired capacity to promote neovascularization in vitro and in vivo compared with those isolated from healthy controls.

View Article and Find Full Text PDF
Article Synopsis
  • High population density and tourism in Southeast Asia raise the risk of mpox due to close interactions among people.
  • Wastewater testing in six countries showed the presence of Monkeypox virus (MPXV) DNA, indicating that the virus is spreading locally.
  • This finding is crucial for healthcare providers to identify cases and manage resources effectively, like testing and vaccines, especially in countries with limited resources.
View Article and Find Full Text PDF

Introduction: Aortic pulse wave velocity (Ao-PWV) predicts cardiovascular and kidney disease in type 2 diabetes (T2D). Klotho is a circulating antiaging hormone (sKlotho) with putative cardiorenal protective effects. The relationship between sKlotho and Ao-PWV in diabetic kidney disease (DKD) is unknown.

View Article and Find Full Text PDF

Zinc (Zn) has antioxidant, anti-inflammatory and anti-proliferative actions, with Zn dysregulation associated with coronary ischemia/reperfusion injury and smooth muscle cell dysfunction. As the majority of studies concerning Zn have been conducted under non-physiological hyperoxic conditions, we compare the effects of Zn chelation or supplementation on total intracellular Zn content, antioxidant NRF2 targeted gene transcription and hypoxia/reoxygenation-induced reactive oxygen species generation in human coronary artery smooth muscle cells (HCASMC) pre-adapted to hyperoxia (18 kPa O) or normoxia (5 kPa O). Expression of the smooth muscle marker SM22-α was unaffected by lowering pericellular O, whereas calponin-1 was significantly upregulated in cells under 5 kPa O, indicating a more physiological contractile phenotype under 5 kPa O.

View Article and Find Full Text PDF

Zinc is an important component of cellular antioxidant defenses and dysregulation of zinc homeostasis is a risk factor for coronary heart disease and ischemia/reperfusion injury. Intracellular homeostasis of metals, such as zinc, iron and calcium are interrelated with cellular responses to oxidative stress. Most cells experience significantly lower oxygen levels in vivo (2-10 kPa O) compared to standard in vitro cell culture (18kPa O).

View Article and Find Full Text PDF

Current evidence suggests that severity and mortality of COVID-19 is higher in men than in women, whereas women might be at increased risk of COVID-19 reinfection and development of long COVID. Differences between sexes have been observed in other infectious diseases and in the response to vaccines. Sex-specific expression patterns of proteins mediating virus binding and entry, and divergent reactions of the immune and endocrine system, in particular the hypothalamic-pituitary-adrenal axis, in response to acute stress might explain the higher severity of COVID-19 in men.

View Article and Find Full Text PDF

Although human dermis contains distinct fibroblast subpopulations, the functional heterogeneity of fibroblast lines from different donors is under-appreciated. We identified one commercially sourced fibroblast line (c64a) that failed to express α-smooth muscle actin (α-SMA), a marker linked to fibroblast contractility, even when treated with transforming growth factor-β1 (TGF-β1). Gene expression profiling identified insulin-like growth factor 1 (IGF1) as being expressed more highly, and Asporin (ASPN) and Wnt family member 4 (WNT4) expressed at lower levels, in c64a fibroblasts compared to three fibroblast lines that had been generated in-house, independent of TGF-β1 treatment.

View Article and Find Full Text PDF

COVID-19 disproportionately affects older people, with likelihood of severe complications and death mirroring that of other age-associated diseases. Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) has been shown to delay or reverse many age-related phenotypes, including declining immune function. Rapamycin (sirolimus) and rapamycin derivatives are US Food and Drug Administration-approved inhibitors of mTORC1 with broad clinical utility and well established dosing and safety profiles.

View Article and Find Full Text PDF

Neurological disorders are the leading cause of disability and the second largest cause of death worldwide. Despite significant research efforts, neurology remains one of the most failure-prone areas of drug development. The complexity of the human brain, boundaries to examining the brain directly in vivo, and the significant evolutionary gap between animal models and humans, all serve to hamper translational success.

View Article and Find Full Text PDF

Dermal fibroblasts play a key role in maintaining homoeostasis and functionality of the skin. Their contractility plays a role in changes observed during ageing, especially in processes such as wound healing, inflammation, wrinkling and scar tissue formation as well as structural changes on extracellular matrix. Although alternations in skin physiology and morphology have been previously described, there remains a paucity of information about the influence of chronological ageing on dermal fibroblast contractility.

View Article and Find Full Text PDF

Activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway is critical for vascular endothelial redox homeostasis in regions of high, unidirectional shear stress (USS), however the underlying mechanosensitive mediators are not fully understood. The endothelial glycocalyx is disrupted in arterial areas exposed to disturbed blood flow that also exhibit enhanced oxidative stress leading to atherogenesis. We investigated the contribution of glycocalyx sialic acids (SIA) to Nrf2 signaling in human endothelial cells (EC) exposed to atheroprotective USS or atherogenic low oscillatory shear stress (OSS).

View Article and Find Full Text PDF