Aging & Longevity

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.

CONCLUSIONS: Our grounded theory underscores that physical activity and exercise should be regarded as multifaceted processes, which must be considered when promoting physical activity initiatives for older persons. By considering the older person and societal norms and values, we can gather knowledge to design physical exercise interventions that are not only effective but also enjoyable and capable of transforming how individuals perceive themselves as exercising persons.

Aging is a major risk factor for poor outcomes following respiratory infections. In animal models, the most severe outcomes of respiratory infections in older hosts have been associated with an increased burden of senescent cells that accumulate over time with age and create a hyperinflammatory response. Although studies using coronavirus animal models have demonstrated that removal of senescent cells with senolytics, a class of drugs that selectively kills senescent cells, resulted in reduced...

Aging of the brain vasculature plays a key role in the development of neurovascular and neurodegenerative diseases, thereby contributing to cognitive impairment. Among other factors, DNA damage strongly promotes cellular aging, however, the role of genomic instability in brain endothelial cells (EC) and its potential effect on brain homeostasis is still largely unclear. We here investigated how endothelial aging impacts blood-brain barrier (BBB) function by using excision repair cross...

Conventional chemotherapy- and radiotherapy-induced cancer senescence, which is characterized by poor proliferation, drug resistance, and senescence-associated secretory phenotype, has gained attention as contributing to cancer relapse and the development of an immunosuppressive tumor microenvironment. However, the association between cancer senescence and anti-tumor immunity is not fully understood. Here, we demonstrate that senescent cancer cells increase the level of PD-L1 by promoting its...

The fallopian tube undergoes extensive molecular changes during the menstrual cycle and menopause. We use single-cell RNA and ATAC sequencing to construct a comprehensive cell atlas of healthy human fallopian tubes during the menstrual cycle and menopause. Our scRNA-seq comparison of 85,107 pre- and 46,111 post-menopausal fallopian tube cells reveals substantial shifts in cell type frequencies, gene expression, transcription factor activity, and cell-to-cell communications during menopause and...