High levels of soluble RAGE are associated with a greater risk of mortality in COVID-19 patients treated with dexamethasone.

Blood levels of the soluble receptor for advanced glycation end-products (sRAGE) are acutely elevated during the host inflammatory response to infection and predict mortality in COVID-19. However, the prognostic performance of this biomarker in the context of treatments to reduce inflammation is unclear. In this study we investigated the association between sRAGE and mortality in dexamethasone-treated COVID-19 patients.

DPP4 Promotes Human Endothelial Cell Senescence and Dysfunction via the PAR2-COX-2-TP Axis and NLRP3 Inflammasome Activation.

Background: Abnormal accumulation of senescent cells in the vessel wall leads to a compromised vascular function contributing to vascular aging. Soluble DPP4 (dipeptidyl peptidase 4; sDPP4) secretion from visceral adipose tissue is enhanced in obesity, now considered a progeric condition. sDPP4 triggers vascular deleterious effects, albeit its contribution to vascular aging is unknown.

The use of the soluble receptor for advanced glycation-end products (sRAGE) as a potential biomarker of disease risk and adverse outcomes.

The soluble receptor for advanced glycation end-products (sRAGE) has been classically considered a sink for pro-inflammatory RAGE ligands and as such has been associated with protection from inflammatory stress and disease. An alternative, though not mutually exclusive view is that high levels of sRAGE in circulation reflect the overstimulation of cell surface RAGE which if persistent, lead to the amplification of pro-inflammatory processes and the exacerbation of pathological states. With these two scenarios in mind this review focuses on the potential role of sRAGE as a prospective biomarker of disease risk and adverse outcomes.

A robust machine learning framework to identify signatures for frailty: a nested case-control study in four aging European cohorts.

Phenotype-specific omic expression patterns in people with frailty could provide invaluable insight into the underlying multi-systemic pathological processes and targets for intervention. Classical approaches to frailty have not considered the potential for different frailty phenotypes. We characterized associations between frailty (with/without disability) and sets of omic factors (genomic, proteomic, and metabolomic) plus markers measured in routine geriatric care.

Higher sRAGE Levels Predict Mortality in Frail Older Adults with Cardiovascular Disease.

Introduction: The evidence that blood levels of the soluble receptor for advanced glycation end products (sRAGE) predict mortality in people with cardiovascular diseases (CVD) is inconsistent. To clarify this matter, we investigated if frailty status influences this association.

Methods: We analysed data of 1,016 individuals (median age, 75 years) from 3 population-based European cohorts, enrolled in the FRAILOMIC project.

Oxidative stress, telomeres and cellular senescence: What non-drug interventions might break the link?

Telomeres are higher order structures that cap and protect chromosome ends. Telomeric DNA naturally shortens during somatic cell division and as a result of oxidative stress. Excessive shortening disrupts the integrity of the telomere, causing cellular senescence, one of the hallmarks of organismal ageing.

Increased levels of soluble Receptor for Advanced Glycation End-products (RAGE) are associated with a higher risk of mortality in frail older adults.

Objective: to evaluate the relationship between serum levels of the soluble Receptor for Advanced Glycation End-products (sRAGE) and mortality in frail and non-frail older adults.

Methods: we studied 691 subjects (141 frail and 550 non-frail) with a median age of 75 years from two population-based cohorts, the Toledo Study of Healthy Aging and the AMI study, who were enrolled to the FRAILOMIC initiative. Multivariate Cox proportional hazards regression and Kaplan-Meier survival analysis were used to assess the relationship between baseline sRAGE and mortality.

The angiotensin-(1-7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation.

Endothelial cell senescence is a hallmark of vascular aging that predisposes to vascular disease. We aimed to explore the capacity of the renin-angiotensin system (RAS) heptapeptide angiotensin (Ang)-(1-7) to counteract human endothelial cell senescence and to identify intracellular pathways mediating its potential protective action. In human umbilical vein endothelial cell (HUVEC) cultures, Ang II promoted cell senescence, as revealed by the enhancement in senescence-associated galactosidase (SA-β-gal+) positive staining, total and telomeric DNA damage, adhesion molecule expression, and human mononuclear adhesion to HUVEC monolayers.

Association between plasma CCL11 (eotaxin-1) and cognitive status in older adults: Differences between rural and urban dwellers.

The chemokine CCL11 has been implicated in age-related cognitive deterioration in mice, yet evidence on the relationship between CCL11 and cognitive function in humans is limited. This study explored associations between CCL11 and cognition in rural and urban community-dwelling older adults. Participants were 515 urban dwellers from the 3C-Bordeaux cohort and 318 rural dwellers from the AMI cohort.

Evidence for a role of TRIB3 in the regulation of megakaryocytopoiesis.

Megakaryocytopoiesis is a complex differentiation process driven by the hormone thrombopoietin by which haematopoietic progenitor cells give rise to megakaryocytes, the giant bone marrow cells that in turn break down to form blood platelets. The Tribbles Pseudokinase 3 gene (TRIB3) encodes a pleiotropic protein increasingly implicated in the regulation of cellular differentiation programmes. Previous studies have hinted that TRIB3 could be also involved in megakaryocytopoiesis but its role in this process has so far not been investigated.

The age-dependent association between aortic pulse wave velocity and telomere length.

Key Points: Age significantly modifies the relationship between aortic pulse wave velocity and telomere length. The differential relationships observed between aortic pulse wave velocity and telomere length in younger and older individuals suggest that the links between cellular and vascular ageing reflect a complex interaction between genetic and environmental factors acting over the life-course.

Abstract: Ageing is associated with marked large artery stiffening.

The Longitudinal Relationship Between Cortisol Responses to Mental Stress and Leukocyte Telomere Attrition.

Context: Chronic psychological stress has been associated with shorter telomeres, but the underlying mechanisms are poorly understood. One possibility is that the neuroendocrine responses to stress exposure are involved.

Objective: To test the hypothesis that greater cortisol responsivity to acute stressors predicts more rapid telomere attrition.

In Search of 'Omics'-Based Biomarkers to Predict Risk of Frailty and Its Consequences in Older Individuals: The FRAILOMIC Initiative.

An increase in the number of older people experiencing disability and dependence is a critical aspect of the demographic change that will emerge within Europe due to the rise in life expectancy. In this scenario, prevention of these conditions is crucial for the well-being of older citizens and for the sustainability of our healthcare systems. Thus, the diagnosis and management of conditions like frailty, which identifies the people at the highest risk for developing those adverse outcomes, is of critical relevance.

Shorter telomeres with high telomerase activity are associated with raised allostatic load and impoverished psychosocial resources.

Recent work has linked psychological stress with premature cellular aging as indexed by reduced leukocyte telomere length. The combination of shorter telomeres with high telomerase activity (TA) may be indicative of active cell stress. We hypothesized that older individuals characterized by shorter telomeres with high TA in unstimulated leukocytes would show signs of high allostatic load and low levels of protective psychosocial resources.

SIRT6 protects human endothelial cells from DNA damage, telomere dysfunction, and senescence.

Aims: Although endothelial cell senescence is known to play an important role in the development of cardiovascular pathologies, mechanisms that attenuate this process have not been extensively investigated. The aim of this study was to investigate whether SIRT6, a member of the sirtuin family of NAD(+)-dependent protein deacetylases/ADP-ribosyltransferases, protects endothelial cells from premature senescence and dysfunction, and if so which is its mode of action.

Methods And Results: mRNA expression analysis demonstrated comparable levels of SIRT1 and SIRT6 transcripts in endothelial cells derived from different vascular beds and significantly higher levels of SIRT6 in these cells relative to those in haematopoietic progenitor cells.

Short sleep duration is associated with shorter telomere length in healthy men: findings from the Whitehall II cohort study.

Background: Shorter telomere length and poor sleep are more prevalent at older ages, but their relationship is uncertain. This study explored associations between sleep duration and telomere length in a sample of healthy middle and early old age people.

Methods: Participants were 434 men and women aged 63.

Hostility and cellular aging in men from the Whitehall II cohort.

Background: Hostility is associated with a significantly increased risk of age-related disease and mortality, yet the pathophysiological mechanisms involved remain unclear. Here we investigated the hypothesis that hostility might impact health by promoting cellular aging.

Methods: We tested the relationship between cynical hostility and two known markers of cellular aging, leukocyte telomere length (TL) and leukocyte telomerase activity (TA), in 434 men and women from the Whitehall II cohort.

Educational attainment but not measures of current socioeconomic circumstances are associated with leukocyte telomere length in healthy older men and women.

Low socioeconomic status (SES) may be associated with accelerated biological aging, but findings relating SES with telomere length have been inconsistent. We tested the hypotheses that shorter telomere length and telomerase activity would be related more robustly to education, an early life indicator of socioeconomic position, than to current indicators of socioeconomic circumstances. Healthy men and women aged 53-76 years from the Whitehall II epidemiological cohort provided blood samples from which telomere length was assessed in 448 and telomerase activity in 416.

Honey, health and longevity.

Honey is a broad spectrum antimicrobial agent which can enhance wound healing. A beneficial effect in cancer has been shown in cell cultures and in animal studies and a number of further nutritional and physiological effects of relevance to health and function have been shown for honey. A representative sub-sample of 665 men within the Caerphilly Cohort kept a weighed dietary record for seven days.

Protocols to detect senescence-associated beta-galactosidase (SA-betagal) activity, a biomarker of senescent cells in culture and in vivo.

Normal cells can permanently lose the ability to proliferate when challenged by potentially oncogenic stress, a process termed cellular senescence. Senescence-associated beta-galactosidase (SA-betagal) activity, detectable at pH 6.0, permits the identification of senescent cells in culture and mammalian tissues.

Vascular endothelial senescence: from mechanisms to pathophysiology.

Most mitotically competent mammalian cell types can react to stress by undergoing a phenotypically distinctive and permanent form of growth arrest called "cellular senescence." This response has been extensively characterized in cell culture and more recently it has been found to occur also in vivo in a number of tissues. In this review I will present the case for the occurrence of senescence in the vascular endothelium.

Mechanisms of endothelial senescence.

When endothelial cells from different vascular beds are grown in culture they show a limited capacity to divide, eventually entering into a permanent and phenotypically distinctive non-dividing state referred to as 'replicative senescence'. Replicative senescence is thought to result from progressive shortening of telomeric DNA and consequent telomere dysfunction. More recently, it has been realised that senescence can also be induced by a variety of insults, including those causing intracellular oxidative stress.