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Recent advancements in cancer immunotherapy have improved patient outcomes, yet responses to immunotherapy remain moderate. Immunosenescence has been shown to contribute to the development and progression of various diseases; however, its specific role in solid tumors has not been fully delineated. Here we conducted a phase 2 clinical trial involving 51 patients with cancer undergoing neoadjuvant chemoimmunotherapy and applied single-cell RNA as well as TCR and BCR sequencing on tumor and blood...

BACKGROUND: Chronic pain (CP) and psychiatric disorders (PD) are common in older adults, and they both may significantly impact patients' functioning and quality of life. However, research on the prevalence and impact of CP in people with PD remains limited- especially in older adults- and psychiatric care often neglects somatic comorbidities.

Each year, billions of animals migrate across the globe on diverse spatial and temporal scales. Migration behavior thus plays a fundamental role in the life cycle and Darwinian fitness of many organisms. While the influence of migration on early-life survival and reproduction is well documented, its effects on senescence (aging) in advanced age remain largely unexplored. Using a unique 44-y ring-resighting dataset from a long-lived, partially migratory bird species, the Greater Flamingo...

The fast-paced improvements in mortality in high-income countries since the early 1900s have led to a sustained increase in life expectancy. However, whether this linear trend will continue or life expectancy gains will decelerate in the near future remains unclear. To answer this question, we apply multiple established and recently developed mortality forecasting methods to estimate cohort life expectancy for individuals born between 1939 and 2000 in 23 high-income countries. Across all...

NAD + homeostasis is an important determinant of lifespan and may be a key mechanism of caloric restriction (CR) expansion of lifespan. Ketone bodies such as beta-hydroxybutyrate (BHB) that regulate NAD + abundance and NAD + precursors such nicotinamide mononucleotide (NMN), are known to extend life in experimental animals and ameliorate age-related conditions in humans. We tested the hypothesis that chronic BHB and NMN exposure can extend lifespan similarly to the effect of CR treatment in a...

The spreading of MAPT/Tau pathology is closely associated with the progression of neurodegeneration and cognitive decline in Alzheimer disease and other tauopathies. A key event in this process is the rupture of endolysosomal vesicles following the intercellular transfer of MAPT/Tau aggregates, releasing the transferred MAPT/Tau species into the cytosol where they can promote the aggregation of endogenous MAPT/Tau. However, understanding of the cellular pathways involved in this process remains...

CONCLUSION: Compared to patients with other serious illnesses, a relatively large portion of patients with advanced cancer reported that their treatment discordantly focused on longevity over comfort despite their goal to prioritize comfort over longevity.

Aging and neurodegenerative diseases are characterized by cognitive decline, impaired neuroplasticity, and epigenetic dysregulation. Curcumin, a bioactive polyphenol derived from Curcuma longa, has gained significant attention for its neuroprotective properties, particularly in enhancing cognitive function through epigenetic mechanisms. This review explores the multifaceted role of curcumin in modulating key molecular pathways involved in neuroplasticity, including histone modifications, DNA...

Despite congressional resistance, agency aims to cut research spending now

Machines still face hurdles in identifying fresh research paths, study suggests

The hippocampus has been widely implicated in the neurobiology of neurologic and psychiatric disorders. This structure is heterogeneous, however, and comprised of multiple subregions that have different connectivity patterns and functions. Better understanding how these subregions are affected by age and their relationship with neurocognition could provide information regarding how alterations in normal trajectories play a role in disease and cognitive dysfunction. Using natural splines we...

Emerging digitally delivered non-pharmacological interventions (dNPIs) offer scalable, low-risk solutions for enhancing cognitive function in older adults, yet their effectiveness remains inconsistent due to a lack of personalization and precise mechanisms of action. Generic, population-based designs often fail to predict individual gains, underscoring the need for more tailored approaches. To address this, we propose a closed-loop human-machine interface (HMI) framework for personalizing dNPIs...

Cellular senescence restrains the expansion of neoplastic cells through several layers of regulation. We report that the histone H3-specific demethylase KDM4 is expressed as human stromal cells undergo senescence. In clinical oncology, upregulated KDM4 and diminished H3K9/H3K36 methylation correlate with poorer survival of patients with prostate cancer after chemotherapy. Global chromatin accessibility mapping via assay for transposase-accessible chromatin with high-throughput sequencing, and...

Aging is a multifactorial biological process resulting in physiological and cellular decline. However, our understanding of age-related changes in 3D genome organization and the effect of external interventions on this process remains limited. Here, we describe alterations in the landscape of the 3D chromatin interactome upon aging, utilizing the low-input promoter capture Hi-C (liCHi-C) technique with mouse hippocampal neurons. We also integrated liCHi-C data with RNA sequencing (RNA-seq) data...

CONCLUSIONS: Liver chemistries in community-dwelling older adults with normal nutritional status were within the normal reference range used for adults. There were small but statistically significant differences with age, sex, and intensity of statin therapy. ALT declined with age, and further prospective studies are required to determine cut-offs for increased risk of adverse clinical outcomes.

ATP13A2 is an endolysosomal polyamine transporter mutated in several neurodegenerative conditions involving lysosomal defects, including Parkinson's disease (PD). While polyamines are polybasic and polycationic molecules that play pleiotropic cellular roles, their specific impact on lysosomal health is unknown. Here, we demonstrate lysosomal polyamine accumulation in ATP13A2 knockout (KO) cell lines and human induced pluripotent stem cell (iPSC)-derived neurons. Primary polyamine storage caused...

The Haber-Bosch process is used for industrial ammonia production worldwide, and it accounts for ~2% of the global energy consumption and 1.3% anthropogenic carbon footprint. Ammonia synthesis under ambient conditions with minimum carbon emission is highly desired, but it is still in the initial stage. Herein, we report a cobalt-based catalyst for ammonia continuous synthesis under ambient conditions via mechanochemistry. To describe mechanochemistry of ammonia synthesis, density functional...