Aging & Longevity

BACKGROUND: Dementia and Alzheimer's disease are the leading cause of death in England, with prevalence estimated to rise with an ageing population. 2021 cost estimates were £25 billion, rising to an estimated £47 billion in 2050. Brain health clinics (BHC) offer patients with memory concerns access to higher quality memory assessment and imaging than memory clinics, which are the usual care. BHCs aim to offer patients a more accurate and timely diagnosis, resulting in more specific treatment...

BACKGROUND: There is an ongoing debate about whether mental wellbeing follows a U-shaped pattern across the lifespan, with a universal low point during midlife. However, existing research largely looks at average distributions of mental health problems and does not consider the underlying trajectories and social determinants. We investigate the social factors linked to changes in mental health during midlife.

BACKGROUND: Polygenic Risk Scores (PRSs) have been proposed as a mechanism for risk-stratification of screening, increasing efficiency and enabling extension of existing programmes to improve survival in our aging population. We sought to model the impact of three hypothetical programmes of annual breast cancer screening in women aged 40-49 years: screening the PRS-defined high-risk quintile, screening the oldest quintile, and screening the full population.

BACKGROUND: Age-related mobility issues and frailty are a major public health concern because of an increased risk of falls. Subjective assessment of fall risk in the clinic is limited, failing to account for an individual's habitual activities in the home or community. Equally, objective mobility trackers for use in the home and community lack extrinsic (ie, environmental) data capture to comprehensively inform fall risk. We propose a contemporary approach that combines artificial intelligence...

BACKGROUND: The Welsh government recently set a target to be smoke-free by 2030, which means reducing the prevalence of tobacco smoking in adults to 5% by then. The goal is to improve health and population life expectancy. To support this strategy, we identified profile groups with different sets of socioeconomic and demographic characteristics within the population of smokers. We compared these profiles to those identified in the ex-smoker population to provide a broader understanding of...

BACKGROUND: Multimorbidity, defined as the presence of two or more long-term conditions, is a growing public health challenge, especially in terms of prevention and accumulation of long-term conditions among particular population cohorts. To date, efforts to understand multimorbidity has focused mainly on specific disease combinations, with little known about the sociodemographic factors associated with it. The study aimed to assess the factors associated with multimorbidity in England.

BACKGROUND: The COVID-19 pandemic resulted in extensive disruption to the delivery of elective health services. Official figures of NHS waiting lists in England do not account for patients on the hidden waiting list (ie, patients who have symptoms or disease requiring elective procedures who have not been placed on the waiting list due to pandemic-related disruption). The aim of this study was to model the elective procedure backlog in England, including the hidden waiting list.

BACKGROUND: Cancer is an age-related condition, but changes to modifiable lifestyle-related behaviours, including physical activity, could impact risk. While step count is an accessible metric of activity for older adults, its association with cancer risk remains poorly understood. We investigated the association between accelerometer-measured total activity, step count, and cancer risk.

The age-related decline in immunity reduces the effectiveness of vaccines in older adults. Immunosenescence is associated with chronic, low-grade inflammation, and the accumulation of senescent cells. The latter express Bcl-2 family members (providing resistance to cell death) and exhibit a pro-inflammatory, senescence-associated secretory phenotype (SASP). Preexisting senescent cells cause many aging-related disorders and therapeutic means of eliminating these cells have recently gained...

Mutations in the Presenilin (PSEN) genes are the most common cause of early-onset familial Alzheimer's disease (FAD). Studies in cell culture, in vitro biochemical systems, and knockin mice showed that PSEN mutations are loss-of-function mutations, impairing γ-secretase activity. Mouse genetic analysis highlighted the importance of Presenilin (PS) in learning and memory, synaptic plasticity and neurotransmitter release, and neuronal survival, and Drosophila studies further demonstrated an...

The mRNA transcript of the human STMN2 gene, encoding for stathmin-2 protein (also called SCG10), is profoundly impacted by TAR DNA-binding protein 43 (TDP-43) loss of function. The latter is a hallmark of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Using a combination of approaches, including transient antisense oligonucleotide-mediated suppression, sustained shRNA-induced depletion in aging mice, and germline deletion, we show that stathmin-2 has an...

Aging is a strong risk factor for atherosclerosis and induces accumulation of memory CD8^(+) T cells in mice and humans. Biological changes that occur with aging lead to enhanced atherosclerosis, yet the role of aging on CD8^(+) T cells during atherogenesis is unclear. In this study, using femle mice, we found that depletion of CD8^(+) T cells attenuated atherogenesis in aged, but not young, animals. Furthermore, adoptive transfer of splenic CD8^(+) T cells from aged wild-type, but not young...

The power conversion efficiency (PCE) of inverted perovskite solar cells (PSCs) is still lagging behind that of conventions PSCs in part because of inefficient carrier transport and poor morphology of hole transport layers (HTLs). We optimized self-assembly of [4-(3,6-dimethyl-9H-carbazol-9-yl)butyl]phosphonic acid (Me-4PACz) onto nickel oxide (NiO(x)) nanoparticles as an HTL through treatment with hydrogen peroxide, which created a more uniform dispersion of nanoparticles with high conductivity...

CONCLUSIONS: Irregular sleep-wake patterns are associated with higher mortality risk.

Orexigenic neurons expressing agouti-related protein (AgRP) and neuropeptide Y in the arcuate nucleus (ARC) of the hypothalamus are activated in response to dynamic variations in the metabolic state, including exercise. We previously observed that carnitine palmitoyltransferase 1a (CPT1A), a rate-limiting enzyme of mitochondrial fatty acid oxidation, is a key factor in AgRP neurons, modulating whole-body energy balance and fluid homeostasis. However, the effect of CPT1A in AgRP neurons in aged...

The biological process of aging is thought to result in part from accumulation of senescent cells in organs. However, the present study identified a subset of fibroblasts and smooth muscle cells which are the major constituents of organ stroma neither proliferative nor senescent in tissues of the elderly, which we termed "mid-old status" cells. Upregulation of pro-inflammatory genes (IL1B and SAA1) and downregulation of anti-inflammatory genes (SLIT2 and CXCL12) were detected in mid-old cells....

Coronavirus disease 2019 (COVID-19) remains a significant public health threat due to the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants to evade the immune system and cause breakthrough infections. Although pathogenic coronaviruses such as SARS-CoV-2 and Middle East respiratory syndrome (MERS)-CoV lead to severe respiratory infections, how these viruses affect the chromatin proteomic composition upon infection remains largely uncharacterized. Here, we use our...

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Due to their long lifespan, trees and bushes develop higher order of branches in a perennial manner. In contrast to a tall tree, with a clearly defined main stem and branching order, a bush is shorter and has a less apparent main stem and branching pattern. To address the developmental basis of these two forms, we studied several naturally occurring architectural variants in silver birch (Betula pendula). Using a candidate gene approach, we identified a bushy kanttarelli variant with a...

Obesity and aging share comorbidities, phenotypes, and deleterious effects on health that are associated with chronic diseases. However, distinct features set them apart, with underlying biology that should be explored and exploited, especially given the demographic shifts and the obesity epidemic that the world is facing.