Aging & Longevity

Functional ability and intrinsic capacity (IC) have been proposed as determinants of healthy aging, but the extent to which these indicators are affected by biological aging remains unknown. We explored the association of biological age acceleration (BAA) with functional ability and IC in older adults with physical and cognitive impairments. This cross-sectional study used data from 163 individuals (84.0 ± 5.2 years [range 72-99], 61.8% women) of the COGFRAIL cohort. Functional ability on basic...

Uracil incorporation into DNA, as a result of nucleotide pool imbalances or cytosine deamination (e.g., through APOBEC3A/3B), can result in replication stress and is the most common source of mutations in cancer and aging. Despite the critical role of uracil in genome instability, cancer development, and cancer therapy, only now is there emerging data on its impact on fundamental processes such as DNA replication and genome stability. Removal of uracil from DNA by base excision repair (BER) can...

Recent studies suggest that vascular senescence and its associated inflammation fuel the inflammaging to favor atherogenesis; whether these pathways can be therapeutically targeted in coronary artery disease (CAD) patients remains unknown. In a randomized, double-blind trial, 97 patients (78 men) undergoing coronary artery bypass graft surgery were treated with either quercetin (500 mg twice daily, 47 patients) or placebo (50 patients) for two days pre-surgery through hospital discharge. Primary...

We investigated the changes in home care clients' vision and hearing over 18 months and examined the role of sensory impairments in maintaining their functioning. We used data from the Finnish Resident Assessment Instrument (RAI) database (n = 7013). Sensory impairment status was categorized by type (single or dual) and severity (mild or moderate/severe). The association between sensory impairment and functioning over 18 months was examined using binary logistic regression analysis with...

Neurodegenerative diseases (NDDs) and other age-related disorders have been classically defined by a set of key pathological hallmarks. Two of these hallmarks, cell cycle dysregulation (CCD) and nucleocytoplasmic transport (NCT) defects, have long been debated as being either causal or consequential in the pathology of accelerated aging. Specifically, aberrant cell cycle activation in post-mitotic neurons has been shown to trigger neuronal cell death pathways and cellular senescence....

CONCLUSIONS: ABSs had a reduced risk of cognitive decline during the pandemic compared with that of the other groups.

CONCLUSIONS: There is a significant association between tooth count and frailty, particularly in those with 20 or fewer teeth. Policymakers should prioritize oral health within aging populations by promoting early preventive care and education to mitigate frailty risk. Robust, large-scale studies are needed to guide evidence-based interventions and public health policy.

BACKGROUND: Hypertension, a major concern for older adults, contributes to morbidity and mortality by increasing the risk of cardiovascular disease, stroke, kidney dysfunction, and cognitive decline. A healthy diet plays a vital role in limiting chronic disease progression in aging populations.

CONCLUSIONS: This study suggests a potential causal associations between molecular markers of biological aging and orthopedic diseases, suggesting avenues for future research into the underlying mechanisms.

Immersive virtual reality (IVR) offers significant potential for aging research, providing a controlled yet ecologically valid platform for studying cognitive, emotional, and motor processes, as well as supporting interventions and diagnostic assessments in older adults. However, its usability can be hindered by age-related sensory, motor, and cognitive changes, which may contribute to anxiety, disorientation, and reduced task engagement. In this narrative review, we examine the challenges older...

Alzheimer's disease (AD) is the most prevalent form of dementia worldwide. It is a multifaceted condition resulting from interplay of genetic mutations (e.g., APP, PSEN1, PSEN2) that account for less than 5% of cases, several genetic risk variants such as APOE4, TREM2, CD33, CLU, SORL1, and CR1 contribute to disease susceptibility and epigenetic factors, which may mediate the influence of environmental and lifestyle factors over time. Other critical contributors such as aging, protein misfolding...

Aging is associated with increased retinal cell apoptosis, which contributes to decreases in retinal function. Apoptotic retinal cell clearance relies on microglial efferocytosis, but the impact of aging on this process has not been fully elucidated. In this study, we aimed to shed light on this by using single-cell RNA sequencing (sc-RNA-seq) to compare young and aged mouse retinal transcriptional profiles, in which 74,412 retinal cells from young and aged mice were classified into 10...

The aberrant expression of S100A11 has been identified in various malignancies but its functional roles and underlying mechanisms in colorectal cancer (CRC) have not been fully elucidated. Therefore, this study was designed to investigate the expression of S100A11 and its functional significance in CRC, indicating that S100A11 is significantly upregulated and correlates with poor survival outcomes in CRC. Functionally, S100A11 knockdown in CRC cell lines inhibited cell proliferation, invasion,...

Large-scale genomic studies focusing on the genetic contribution to human aging have mostly relied on cross-sectional data. With the release of longitudinally curated aging phenotypes by the UK Biobank (UKBB), it is now possible to study aging over time at genome-wide scale. In this work, we evaluated the suitability of competing models of change in realistic simulation settings, performed genome-wide association scans on simulation-validated measures of age-related deweekcline, and followed up...

Obesity-related osteoarthritis (OA) and the molecular mechanisms governing multiple joint structural changes that occur with obesity are not well understood. This study investigated the progression of obesity in mice and validated the results using human joint samples post-arthroplasty. The results show that obesity is associated with the degeneration of the cartilage layer and abnormal remodeling of the subchondral bone layer, and this occurs alongside aging and DNA damage in chondrocytes,...

CONCLUSIONS: LGBQ women were more likely than straight women to be exposed to breast cancer risk factors, which were compounded by lower screening and facing health care access barriers. It is crucial to identify interventions for screening and risk reduction that are accessible and effective for LGBQ women, particularly bisexual/queer women and those aging into screen-eligibility.

Replicative senescence occurs in response to shortened telomeres and is triggered by ATM and TP53-mediated DNA damage signaling that blocks replication. hTERT lengthens telomeres, which is thought to block damage signaling and the onset of senescence. We find that normal diploid fibroblasts expressing hTERT mutants unable to maintain telomere length do not initiate DNA damage signaling and continue to replicate, despite having telomeres shorter than senescent cells. The TRF1 and TRF2 DNA binding...

Aging-related retinal degeneration and vision loss have been severely affecting the elderly worldwide. Previously, we showed that the m⁶A reader YTHDF2 is a negative regulator for dendrite development and protection of retinal ganglion cells (RGC) in mice. Here, we further show that conditional ablation of Ythdf2 protects the retina from RGC dendrite shrinking and vision loss in aged mice. Additionally, we identify Hspa12a and Islr2 as the potential YTHDF2 target mRNAs mediating these effects....

"Biological aging clocks"-composite molecular markers thought to capture an individual's biological age-have been traditionally developed through bulk-level analyses of mixed cells and tissues. However, recent evidence highlights the importance of gaining single-cell-level insights into the aging process. Microglia are key immune cells in the brain shown to adapt functionally in aging and disease. Recent studies have generated single-cell RNA-sequencing (scRNA-seq) datasets that...

The X-linked histone demethylase, UTX (KDM6A), is a master regulator of gene enhancers, though its role in self-renewing epithelia like the skin is not well understood. Here, we find that UTX is a key regulator of skin differentiation via the regulation of retinoic acid (RA) signaling, an essential metabolic pathway in both skin homeostasis, as well as in the treatment of an array of skin conditions ranging from cancer and acne to aging. Through deletion of Utx in the skin, we demonstrate direct...