Aging & Longevity

The mammalian dentate gyrus (DG) is involved in certain forms of learning and memory, and DG dysfunction has been implicated in age-related diseases. Although neurogenic potential is maintained throughout life in the DG as neural stem cells (NSCs) continue to generate new neurons, neurogenesis decreases with advancing age, with implications for age-related cognitive decline and disease. In this study, we used single-cell RNA sequencing to characterize transcriptomic signatures of neurogenic...

Declines in physical and cognitive function are common in older adults. The circulating enzyme glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (GPLD1) is elevated after exercise and has been associated with improved cognitive function when administered to aged mice. The purpose of this study was to investigate the relationship between GPLD1 and both cognitive function and brain structure/function in older adults with either high or low levels of physical activity. Healthy men and...

Cinnamon, renowned for its aromatic flavor, represents one of the most widely used spices worldwide. Cinnamon is also considered beneficial to human health with therapeutic potential for treating various diseases, ranging from diabetes and cancer to neurodegenerative diseases. However, the mechanisms underlying cinnamon's health benefits remain elusive. It is also unclear whether cinnamon has any role in aging. Using C. elegans as a model, here we show that feeding worms cinnamaldehyde (CA), the...

Throughout the animal kingdom, several members of the basic helix-loop-helix (bHLH) family act as proneural genes during early steps of nervous system development. Roles of bHLH genes in specifying terminal differentiation of postmitotic neurons have been less extensively studied. We analyze here the function of 5 Caenorhabditis elegans bHLH genes, falling into 3 phylogenetically conserved subfamilies, which are continuously expressed in a very small number of postmitotic neurons in the central...

Accumulation of damaged biomolecules in body tissues is the primary cause of aging and age-related chronic diseases. Since this damage often occurs spontaneously, it has traditionally been regarded as untreatable, with typical therapeutic strategies targeting genes or enzymes being ineffective in this domain. In this report, we demonstrate that an antibody targeting the isoDGR damage motif in lung tissue can guide immune clearance of harmful damaged proteins in vivo, effectively reducing...

Understanding the complex biological process of aging is of great value, especially as it can help develop therapeutics to prolong healthy life. Predicting biological age from gene expression data has shown to be an effective means to quantify aging of a subject, and to identify molecular and cellular biomarkers of aging. A typical approach for estimating biological age, adopted by almost all existing aging clocks, is to train machine learning models only on healthy subjects, but to infer on...

Age-related macular degeneration (AMD) is a progressive disorder and the leading cause of central vision loss. Age is the most important risk factor, followed by genetics and smoking. However, ageing is a complex process, and biological age can deviate from chronological age between individuals and within different organ systems. Initially, we used machine learning to predict the biological age of the immune, cardiovascular, pulmonary, renal, musculoskeletal, metabolic and hepatic systems by...

Increased expression of the cyclin-dependent kinase inhibitor p16Ink4a (p16) is detected in neurons of human Alzheimer's disease (AD) brains and during normal aging. Importantly, selective eliminating p16-expressing cells in AD mouse models attenuates tau pathologies and improves cognition. But whether and how p16 contributes to AD pathogenesis remains unclear. To address this question, we tested whether induction of p16 expression in neurons exacerbates AD pathologies. We created a...

CONCLUSION: Research on microRNA dysregulation, oxidative stress, carboxyl-terminal fragments, small EVs, and mesenchymal stem cell-derived EVs represents a critical frontier in the study of Alzheimer's disease. The role of EV-mediated neuroinflammation in AD is a focal point of ongoing investigation and will likely shape future developments in the field.

A growing literature suggests that declines in sensory/perceptual systems predate cognitive declines in aging, and furthermore, they are highly predictive for developing Alzheimer's disease and Alzheimer's related dementias (ADRD). While vision, hearing, olfaction, and vestibular function have each been shown to be related to ADRD, their causal relations to cognitive declines, how they interact with each other remains to be clarified. Currently, there is substantial debate whether...

Down syndrome (DS), caused by trisomy 21, is characterized by intellectual disability and accelerated aging, with chronic oxidative stress contributing to neurological deficits. REST (Repressor Element-1 Silencing Transcription factor), a crucial regulator of neuronal gene expression implicated in DS neuropathology. This study investigates the neuroprotective potential of lithium, a mood stabilizer with known cognitive-enhancing effects, in restoring levels of REST. Using three pairs of human...

Neuroanatomical sex differences estimated in neuroimaging studies are confounded by total intracranial volume (TIV) as a major biological factor. Employing a matching approach widely used for causal modeling, we disentangled the effect of TIV from sex to study sex-differentiated brain aging trajectories, their relation to functional networks and cytoarchitectonic classes, brain allometry, and cognition. Using data from the UK Biobank, we created subsamples that removed, maintained, or...

Achondroplasia is the most common genetic form of short-limbed skeletal dysplasia (dwarfism). Clinical manifestations and complications can affect individuals across the lifespan, including the need for adaptations for activities of daily living, which can affect quality of life. Current international guidelines focus on symptomatic management, with little discussion regarding potential medication, as therapeutic options were limited at the time of their publication. Vosoritide is the first...

Computerized cognitive training (CCT) is a frontline therapy to prevent or slow age-related cognitive decline. A prerequisite for CCT research to provide clinically relevant improvements in cognition is to understand effective engagement, i.e., the pattern of energy investment that ensures CCT effectiveness. Even though previous studies have assessed whether particular variables (e.g., gamification) predict engagement and/or CCT effectiveness, the field lacks a systematic approach to...

CONCLUSIONS: Some older people living at home with cognitive impairment and/or dementia adapt and accept their limitations as a normal part of the aging process. This affects expectations about their lives at home and their support. Rather than relying on self-direction, supports to live well at home could be enhanced by a greater emphasis on comprehensive needs assessment and more supports to promote reablement and enhance personal and community level participation.

CONCLUSIONS: These findings should stimulate research on the mechanism connecting functional fitness with PWB in older adults. Further, apart from their novelty, the findings could be valuable in providing directions for physical fitness intervention programs targeting mental and physical health for older people.

The development of mechanically robust super-lubrication hydrogel materials with sustained lubricity at high contact pressures is challenging. In this work, inspired by the durable lubricity feature of the earthworm epidermis, a multilevel structural super-lubrication hydrogel (MS-SLH) system, the so-called lubricant self-pumping hydrogel, is developed. The MS-SLH system is manufactured by chemically dissociating a double network hydrogel to generate robust and wrinkled lubrication layer, and...

1,4-Azaborine-based arenes are promising electroluminescent emitters with thermally activated delayed fluorescence (TADF), offering narrow emission spectra and high quantum yields due to a multi-resonance (MR) effect. However, their practical application is constrained by their limited operational stability. This study investigates the degradation mechanism of MR-TADF molecules. Electroluminescent devices incorporating these compounds display varied operational lifetimes, uncorrelated with...

Osteoarthritis is a heterogeneous disorder that is increasingly prevalent largely due to aging and obesity, resulting in a major disease burden worldwide. Knowledge about the underlying aetiology has improved, with increased understanding of the role of genetic factors, the microbiome, and existence of different pain mechanisms. However, this knowledge has not yet been translated into new treatment options. New evidence has questioned the efficacy of recommended treatments, such as therapeutic...

CONCLUSIONS: The pre-hospital living setting could serve as a good indicator of the nutritional intake route upon discharge. It is essential to optimize care in both nursing facilities and hospital settings when caring for older patients with aspiration pneumonia.