Aging & Longevity

The senescence microenvironment, which causes persistent inflammation and loss of intrinsic regenerative abilities, is a main obstacle to effective tissue repair in elderly individuals. In this work, we find that local H(2) supply can remodel the senescence microenvironment by anti-inflammation and anti-senescence effects in various senescent cells from skeletally mature bone. We construct a H(2)-releasing scaffold which can release high-dosage H(2) (911 mL/g, up to 1 week) by electrospraying...

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The induction of cellular reprogramming via expression of the transcription factors Oct4, Sox2, Klf4 and c-Myc (OSKM) can drive dedifferentiation of somatic cells and ameliorate age-associated phenotypes in multiple tissues and organs. However, the benefits of long-term in vivo reprogramming are limited by detrimental side-effects. Here, using complementary genetic approaches, we demonstrated that continuous induction of the reprogramming factors in vivo leads to hepatic and intestinal...

Drugs that selectively kill senescent cells (senolytics) improve the outcomes of cancer, fibrosis and age-related diseases. Despite their potential, our knowledge of the molecular pathways that affect the survival of senescent cells is limited. To discover senolytic targets, we performed RNAi screens and identified coatomer complex I (COPI) vesicle formation as a liability of senescent cells. Genetic or pharmacological inhibition of COPI results in Golgi dispersal, dysfunctional autophagy, and...

Cell-based therapies are essential for tissue regeneration and wound healing during aging. Autologous transplantation of aging cells is ineffective due to their increased senescence and reduced tissue remodeling capabilities. Alternatively, implanting reprogrammed aged cells provides unique opportunities. In this paper, we demonstrate the implantation of partially reprogrammed aged human dermal fibroblasts into in vitro aged skin models for tissue regeneration and wound healing. The partially...

CONCLUSIONS: Our primary meta-analysis confirms that performing exercise >2 weeks results in significant improvements to A[Formula: see text]O2peak, R[Formula: see text]O2peak, and PPO in individuals with SCI. The pooled meta-analysis subgroup comparisons identified that exercise interventions lasting up to 12 weeks yield the greatest change in R[Formula: see text]O2peak. Upper-body aerobic exercise and resistance training also appear the most effective at improving R[Formula: see text]O2peak...

Mild or transient dietary restriction (DR) improves many aspects of health and aging. Emerging evidence from us and others has demonstrated that DR also optimizes the development and quality of immune responses. However, the factors and mechanisms involved remain to be elucidated. Here, we propose that DR-induced optimization of immunological memory requires a complex cascade of events involving memory T cells, the intestinal microbiota, and myeloid cells. Our findings suggest that DR enhances...

The NAD^(+) -dependent deacylase family of sirtuin enzymes have been implicated in biological ageing, late-life health and overall lifespan, though of these members, a role for sirtuin-2 (SIRT2) is less clear. Transgenic overexpression of SIRT2 in the BubR1 hypomorph model of progeria can rescue many aspects of health and increase overall lifespan, due to a specific interaction between SIRT2 and BubR1 that improves the stability of this protein. It is less clear whether SIRT2 is relevant to...

An increasing number of systematic reviews and meta-analyses have been published on the association between oral health and cognitive dysfunction, also known as oral-cognitive links. However, there is great diversity in the oral and cognitive factors included in these studies, with different opinions for clinical practice drawn from the evidence. To understand which oral and cognitive factors are involved in those associations, we conducted an umbrella review of 28 systematic reviews, including...

Vascular aging is a major risk factor for age-related cardiovascular diseases, which have high rates of morbidity and mortality. It is characterized by changes in the blood vessels, such as macroscopically increased vascular diameter and intima-medial thickness, chronic inflammation, vascular calcification, arterial stiffening, and atherosclerosis. DNA damage and the subsequent various DNA damage response (DDR) pathways are important causative factors of vascular aging. Deficient DDR, which may...

Epigenetic drift or "disorder" increases across the mouse lifespan and is suggested to underlie epigenetic clock signals. While the role of epigenetic drift in determining maximum lifespan across species has been debated, robust tests of this hypothesis are lacking. Here, we test if epigenetic disorder at various levels of genomic resolution explains maximum lifespan across four mammal species. We show that epigenetic disorder increases with age in all species and at all levels of genomic...

Baz2B is a regulatory subunit of the ATP-dependent chromatin remodeling complexes BRF1 and BRF5, which control access to DNA during DNA-templated processes. Baz2B has been implicated in several diseases and also in unhealthy ageing, however limited information is available on the domains and cellular roles of Baz2B. To gain more insight into the Baz2B function, we biochemically characterized the TAM (Tip5/ARBP/MBD) domain with the auxiliary AT-hook motifs and the bromodomain (BRD). We observed...

The incidence of neurodegenerative diseases is increasing exponentially worldwide. Parkinson's disease (PD) is a neurodegenerative disease caused by factors like oxidative stress, gene mutation, mitochondrial dysfunction, neurotoxins, activation of microglial inflammatory mediators, deposition of Lewy's bodies, and α- synuclein proteins in the neurons leading to neuroinflammation and neurodegeneration in the substantia nigra. Hence the development of efficacious neuro-therapy is in demand which...

Adult neurogenesis, comprising the generation, differentiation and integration of new neurons in the mature brain, has emerged as a dynamic area of research over decades. The discovery of adult neurogenesis was a paradigm shift to comprehend mechanisms underlying brain plasticity, cognitive function, and neurological disorders. This review deliberates significant findings from articles published over four decades on adult neurogenesis, highlighting key milestones, methodological advances, and...

Dietary restriction is an effective anti-ageing intervention across species. However, the molecular mechanisms from the metabolic aspects of view are still underexplored. Here we show ACS-20 as a key mediator of dietary restriction on healthy ageing from a genetic screen of the C. elegans acyl-CoA synthetase family. ACS-20 functions in the epidermis during development to regulate dietary restriction-induced longevity. Functional transcriptomics studies reveal that elevated expression of...

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BACKGROUND: India is the world's most populous country, and overseas Indians the world's largest diaspora. Many of the more than 1·4 million UK-based Indians will be providing care at a distance for parents living in India. Globalisation has contributed to a shift in India from traditional joint family systems to more nuclear structures. We investigated how commonly Indian parents consider and use long-term care facilities and attitudes to their use.

BACKGROUND: Evidence on workplace bullying and harassment (WBH) in the UK has not used probability-sample surveys with robust mental health assessments. This study aimed to profile the prevalence and nature of WBH in England, identify inequalities in WBH exposure, and quantify adjusted associations with mental health.

BACKGROUND: Dementia's growing impact, especially in ageing societies such as the UK, emphasises the importance of modifiable risk factors as primary prevention targets. Despite this, the temporal progression and the population attributable fraction (PAF) of dementia attributable to these factors remain unclear. This investigation aims to examine the temporal trajectories of the modifiable risk factors for dementia in England from 2004 to 2019.