Aging & Longevity

In the past century, the human Lifespan has doubled. However, this is not equivalent to Healthspan which refers to the number of years spent healthy and free from disease. Women have an additional level of complexity on the path to optimal healthspan where health resilience dramatically decreases following menopause and this is due to their ovaries aging by midlife. It still remains elusive on why and how the ovaries in women, albeit their distinct and vital reproductive functions, start to age...

This study aims to investigate the predictive value of combined phenotypic age and phenotypic age acceleration (PhenoAgeAccel) for benign prostatic hyperplasia (BPH) and develop a machine learning-based risk prediction model to inform precision prevention and clinical management strategies. The study analyzed data from 784 male participants in the US National Health and Nutrition Examination Survey (NHANES, 2001-2008). Phenotypic age was derived from chronological age and nine serum biomarkers....

To evaluate a simplified version of the Clinical Frailty Scale (SCFS) among older adults presenting to the emergency department (ED) with acute dyspnea. In this retrospective single-center cohort study, we included patients from the Acute Dyspnea Study (ADYS) cohort. Severity of illness was assessed using the Medical Emergency Triage and Treatment System (METTS). SCFS was operationalized using existing data on municipal care services from the ADYS database and divided into three levels. SCFS 1:...

Triple-negative breast cancers (TNBCs) lack predictive biomarkers to guide immunotherapy, especially during early-stage disease. To address this issue, we used single-cell RNA sequencing, bulk transcriptomics, and pathology assays on samples from 171 patients with early-stage TNBC receiving chemotherapy with or without immunotherapy. Our investigation identified an enriched subset of interferon (IFN)-induced CD8^(+) T cells in early TNBC samples, which predict immunotherapy nonresponsiveness....

CONCLUSIONS: When evaluating mortality using the NHATS Sensitive files, investigators should consider censoring all participants who are lost to follow-up at the time of the last completed interview, recognizing potential trade-offs in terms of reductions in power and precision.

Aging leads to chronic inflammation that is linked to aging-associated conditions and diseases. Multiple immune pathways become activated during aging, posing a challenge to effectively reduce aging-associated inflammation. SIRT2, an NAD^(+)-dependent deacetylase, suppresses several immune pathways that become activated during aging and may represent an attractive target to broadly dampen aging-associated inflammation. Here, we show that SIRT2 deficiency leads to increased inflammation governed...

The aging population worldwide faces an increasing burden of age-related conditions, with Alzheimer's disease being a prominent neurodegenerative concern. Drug repurposing, the practice of identifying new therapeutic applications for existing drugs, offers a promising avenue for accelerated intervention. In this study, we utilized the yeast Saccharomyces cerevisiae to screen a library of 1760 FDA-approved compounds, both with and without rapamycin, to assess potential synergistic effects on...

Cognitive decline is common in multiple sclerosis (MS), although neural mechanisms are not fully understood. The objective was to investigate the impact of mild cognitive impairment (MCI) on the relationship between resting state functional connectivity (RSFC) and cognitive function in older adults with multiple sclerosis (OAMS) and age matched healthy controls. Participants underwent magnetic resonance imaging (MRI) scans and cognitive assessments. The Oral Symbol Digit Modalities Test (SDMT)...

Beyond their classical functions as redox cofactors, recent fundamental and clinical research has expanded our understanding of the diverse roles of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) in signaling pathways, epigenetic regulation and energy homeostasis. Moreover, NAD and NADP influence numerous diseases as well as the processes of aging, and are emerging as targets for clinical intervention. Here, we summarize safety, bioavailability and...

The global surge in the population of people 60 years and older, including that in China, challenges healthcare systems with rising age-related diseases. To address this demographic change, the Aging Biomarker Consortium (ABC) has launched the X-Age Project to develop a comprehensive aging evaluation system tailored to the Chinese population. Our goal is to identify robust biomarkers and construct composite aging clocks that capture biological age, defined as an individual's physiological and...

CONCLUSIONS: The results emphasize the need for enhanced communication and personalized care to better support frail older adults in engaging in physical activity during hospitalization. Customized advice and tailored physical activities are key to supporting them in staying active and healthy. Effective strategies, teamwork, and resource allocation are needed to meet these older adults' needs and develop interventions that ensure proper care and support.

CONCLUSION: The AMCOHF study will contribute to knowledge about markers to predict an accelerated decline in intrinsic capacity in an early stage. This knowledge is important to deploy prevention strategies at an earlier stage in life then those currently undertaken, ultimately reducing healthcare costs and contributing to a healthy aging population.

The CST (CTC1-STN1-TEN1) complex, a single-stranded DNA (ssDNA) binding complex, is essential for telomere maintenance and genome stability. Depletion of either CTC1 or STN1 results in cellular senescence, while mutations in these components are associated with severe hereditary disorders. In this study, we demonstrate that the direct STN1-CTC1 interaction stabilizes CTC1 by preventing its degradation via TRIM32 mediated ubiquitination. Functional assays indicate that TRIM32 and the CTC1/STN1...

RNA G-quadruplexes (rG4s) are emerging as vital structural elements involved in processes like gene regulation, translation, and genome stability. Found in untranslated regions of messenger RNAs (mRNAs), they influence translation efficiency and mRNA localization. Additionally, rG4s of long noncoding RNAs and telomeric RNA play roles in RNA processing and cellular aging. Despite their significance, the atomic-level folding mechanisms of rG4s remain poorly understood due to their complexity. We...

Peripheral sensory neurons regenerate their axons after injury to regain function, but this ability declines with age. The mechanisms behind this decline are not fully understood. While excessive production of endothelin 1 (ET-1), a potent vasoconstrictor, is linked to many diseases that increase with age, the role of ET-1 and its receptors in axon regeneration is unknown. Using single-cell RNA sequencing, we show that satellite glial cells (SGCs), which completely envelop the sensory neuron...

While BAG3 has been identified as a causative gene for dilated cardiomyopathy, the major pathological events in BAG3-related cardiomyopathy that could be targeted for therapeutic benefit remain to be discovered. Here, we aim to uncover novel pathological events through genetic studies in a zebrafish bag3 cardiomyopathy model. Given the known cardioprotective effects of mtor inhibition and the fact that transcription factor EB (tfeb) encodes a direct downstream phosphorylation target of mTOR...

Epigenetic clocks have emerged as promising biomarkers of aging, but their responsiveness to lifestyle interventions and relevance for short-term changes in cardiometabolic health remain uncertain. In this study, we examined the associations between three epigenetic aging measures (DunedinPACE, PCPhenoAge acceleration, and PCGrimAge acceleration) and a broad panel of cardiometabolic biomarkers in 144 obese participants from the MACRO trial, a 12-month weight-loss dietary intervention comparing...

Immune checkpoint inhibitors (ICIs) can re-active the immune response and induce a complete response in mismatch repair-deficient and microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC). However, most CRCs exhibit proficient mismatch repair and microsatellite stable (pMMR/MSS) phenotypes with limited immunotherapy response because of sparse intratumoral CD8^(+) T-lymphocyte infiltration. Cellular senescence has been reported to involve immune cell infiltration through a...

No abstract

The meninges, consisting of the dura, arachnoid and pia mater that surround the brain and spinal cord, have been recognized from the earliest anatomical studies. First identified in 1787, lymphatic vessels in the dura are now receiving greater attention as their contribution to cerebrospinal fluid (CSF) clearance in diverse neurological conditions is being investigated. New methods have increased the understanding of dural lymphatics, but much is still being learned about their heterogeneity,...