Aging & Longevity

Metabolic disorders such as diabetes and obesity are linked to neurodegenerative diseases, with evidence of lower brain glucose metabolism and insulin resistance in dementia patients. Dietary methionine restriction (MR) is a nutritional intervention that enhances insulin sensitivity and delays ageing-associated metabolic alterations, however, its impact on neurodegenerative diseases is not fully understood. Here, we examined the behavioural and metabolic phenotypes of a murine tauopathy model...

The effect of the serine/glycine-free diet (-SG diet) on colorectal cancer (CRC) remains unclear; meanwhile, programmed death-1 (PD-1) inhibitors are less effective for most CRC patients. Here, we demonstrate that the -SG diet inhibits CRC growth and promotes the accumulation of cytotoxic T cells to enhance antitumor immunity. Additionally, we also identified the lactylation of programmed death-ligand 1 (PD-L1) in tumor cells as a mechanism of immune evasion during cytotoxic T cell-mediated...

Aging presents progressive changes that increase the susceptibility of the central nervous system (CNS) to suffer neurological disorders (NDs). Several studies have reported that an aged brain suffering from NDs shows the presence of pathological forms of tau protein, a microtubule accessory protein (MAP) critical for neuronal function. In this context, accumulative evidence has shown a pivotal contribution of pathological forms of tau to Alzheimer's disease (AD) and tauopathies. However,...

Dietary restriction (DR) extends lifespan in diverse species, from yeast to mammals. However, its underlying mechanisms are not well understood. In this study, through using the tractable model Caenorhabditis elegans, we show a role for the DEAD-box RNA helicase, DDX-23 (homologous to mammal DDX23) as a regulator of healthspan in response to dietary restriction. Meanwhile, DDX-23 is also required for heat and oxidative stress response in C. elegans. Intriguingly, DDX-23 functions in the germline...

Blood-brain barrier disruption (BBBd) occurs in aging, particularly in regions vulnerable to Alzheimer's disease (AD) pathology. However, its relationship to pathological protein accumulation, neurodegeneration, and cognitive impairment in normal aging is unclear. We used dynamic contrast-enhanced MRI (DCE-MRI) and positron emission tomography (PET) imaging in cognitively normal older adults to explore how BBBd correlates with brain atrophy and cognitive function, and whether these relationships...

Introduction Hearing loss is common in ageing populations, but thorough investigation of factors associated with objective hearing loss in otherwise healthy, community dwelling older individuals is rare. We examined prevalence of age-related hearing loss (ARHL) in healthy, community-dwelling older adults, and determined whether sociodemographic, lifestyle or health factors associate with hearing thresholds. Audiometry assessment was investigated with self-reports of hearing loss and hearing...

Cellular growth and organismal development are remarkably complex processes that require the nutrient-responsive kinase mechanistic target of rapamycin complex 1 (mTORC1). Anticipating that important mTORC1 functions remained to be identified, we employed genetic and bioinformatic screening in C. elegans to uncover mechanisms of mTORC1 action. Here, we show that during larval growth, nutrients induce an extensive reprogramming of gene expression and alternative mRNA splicing by acting through...

BACKGROUND: The physiopathology of sarcopenia shares common biological cascades with the aging process, as does any other age-related condition. However, our understanding of the interconnected pathways between diagnosed sarcopenia and aging remains limited, lacking sufficient scientific evidence.

SH-SY5Y human neuroblastoma cells have been extensively used as an in vitro model system in a diverse range of studies involving neurodevelopment, neurotoxicity, neurodegeneration, and neuronal ageing. Both naïve and differentiated phenotypes of SH-SY5Y cells are utilized to model human neurons under in vitro conditions. The process of differentiation causes extensive remodeling of neuronal cells at multiple omic levels, including the epigenome and proteome. In the present investigation, the...

The mechanistic target of rapamycin (mTOR) pathway senses and integrates various environmental and intracellular cues to regulate cell growth and proliferation. As a key conductor of the balance between anabolic and catabolic processes, mTOR complex 1 (mTORC1) orchestrates the symphonic regulation of glycolysis, nucleic acid and lipid metabolism, protein translation and degradation, and gene expression. Dysregulation of the mTOR pathway is linked to numerous human diseases, including cancer,...

Parkinson's disease (PD) is an incurable, progressive and common movement disorder that is increasing in incidence globally because of population aging. We hypothesized that the landscape of rare, protein-altering variants could provide further insights into disease pathogenesis. Here we performed whole-exome sequencing followed by gene-based tests on 4,298 PD cases and 5,512 controls of Asian ancestry. We showed that GBA1 and SMPD1 were significantly associated with PD risk, with replication in...

Diet is a modifiable lifestyle factor with a proven role in cardiovascular disease risk reduction that might also play an important part in cognitive health. Evidence from observational studies has linked certain healthy dietary patterns to cognitive benefits. However, clinical trials of diet interventions have demonstrated either null or, at best, small effects on cognitive outcomes. In this Review, we summarize the currently available evidence from observational epidemiology and clinical...

Earth's old animals are in decline. Despite this, emerging research is revealing the vital contributions of older individuals to cultural transmission, population dynamics, and ecosystem processes and services. Often the largest and most experienced, old individuals are most valued by humans and make important contributions to reproduction, information acquisition and cultural transmission, trophic dynamics, and resistance and resilience to natural and anthropogenic disturbance. These...

Surface passivation has driven the rapid increase in the power conversion efficiency (PCE) of perovskite solar cells (PSCs). However, state-of-the-art surface passivation techniques rely on ammonium ligands that suffer deprotonation under light and thermal stress. We developed a library of amidinium ligands, of interest for their resonance effect-enhanced N-H bonds that may resist deprotonation, to increase the thermal stability of passivation layers on perovskite surfaces. This strategy...

Blue zones, supposed havens of longevity, have become a global brand. But skeptics think they rest on shaky science.

CONCLUSIONS: Videoconference based neuropsychological assessment can be as precise as in-person. Calibration of ability estimates using latent variable measurement models can address measurement differences and generate scores without evidence of systematic bias.

Identifying early predictors of cognitive decline and at-risk individuals is essential for timely intervention and prevention of dementia. This study aimed to detect neurobiological changes and factors related to cognitive performance in the Metropolit 1953 Danish male birth cohort. We analyzed data from 582 participants, aged 57-68 years, using machine learning techniques to group cognitive trajectories into four clusters differentiating high- and low-performing groups. These clusters were then...

Prior studies have shown that interrupting the growth hormone/insulin-like growth factor-I (GH/IGF-I) signaling axis extends laboratory mouse lifespan, but confounding effects of additional gene or hormone deficiencies that exist in commonly used models of GH/IGF-I interruption obscure the specific effect of GH on longevity. We address this issue by using mice with a specific knockout of the GH gene and show that both males and females on a mixed genetic background display extended lifespans...

Production of specialized proresolving mediators (SPMs) during the resolution phase in the acute inflammatory response is key to orchestrating complete resolution. Here, we uncovered a trihydroxy resolvin in fresh human saliva. We identified and determined its complete stereochemistry as 7S,16R,17R-trihydroxy-4Z,8E,10Z,12E,14E,19Z-docosahexaenoic acid (17R-RvD2) using total organic synthesis and matching of physical properties. The 17R-RvD2 was produced by activated human M2-like macrophages,...

NKG2D ligands (NKG2DLs) are broadly expressed in cancer. To target these, we describe an adaptor chimeric antigen receptor (CAR) termed NKG2D/Dap10-12. Herein, T cells are engineered to co-express NKG2D with a fusion protein that comprises Dap10 joined to a Dap12 endodomain. NKG2D/Dap10-12 T cells elicit compelling efficacy, eradicating or controlling NKG2DL-expressing tumors in several established xenograft models. Importantly, durable responses, long-term survival, and rejection of tumor...