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A newly identified protein may be one of the biggest obstacles holding CAR T-cell therapy back. Researchers found that NFIL3 causes these engineered immune cells to become exhausted and lose their cancer-fighting power over time. When NFIL3 was disabled, the cells remained stronger for longer and controlled tumors more effectively in animal models.

A major study suggests that some of the groundwork for brain development may be shaped before birth through a surprising partnership between a baby’s genes and gut microbes. Researchers found that epigenetic changes present at birth can influence how the gut microbiome develops during the first year of life, and certain combinations were linked to early signs of autism and ADHD by age three.

Parkinson's disease (PD) is a progressive neurodegenerative disorder lacking established clinical biomarkers. We performed an exploratory multi‑omics analysis of transcriptome and proteome data from small PD and control cohorts at Huaihe Hospital of Henan University. Using two local datasets, we identified 124 differentially expressed genes (DEGs) and 28 proteins, then performed protein‑protein interaction (PPI) and gene set variation analysis (GSVA). After intersecting with 2,964 DEGs from Gene...

Posttraumatic stress disorder (PTSD) exhibits high rates of comorbidity with Substance Use Disorders (SUDs) and Traumatic Brain Injury (TBI), especially in older adults who are subject to the effects of psychological trauma due to combat exposure, health-related and psychosocial outcomes, and aging. This narrative review explores the associations between PTSD and comorbidities of psychoactive substance abuse and traumatic brain injuries on the incidence of Alzheimer's disease (AD) in veterans...

The DREAM complex has emerged as a central repressor of DNA repair, raising questions as to whether such repression exerts long-term effects on human health. Here we establish that DREAM-associated activity significantly impacts lifetime somatic mutation burden, and that such effects are linked to altered lifespan and age-related disease pathology. First, joint profiling of DREAM-associated activity (quantified from the expression of genes transcriptionally repressed by DREAM) and somatic...

Heart failure (HF) is characterized by a severe disruption of myocardial energy metabolism, with mitochondrial dysfunction standing as a central pathological feature. However, the upstream regulatory mechanisms that drive metabolic remodeling, particularly across distinct HF phenotypes, remain inadequately defined. Mounting evidence reveals that, beyond their metabolic role, mitochondria act as central signaling hubs. This review proposes that dysfunctional mitochondrial-organelle crosstalk is a...

Peripheral immunosenescence has been increasingly implicated in dementia pathogenesis. However, the contributions of specific lymphocyte subsets to cognitive outcomes remain poorly defined, and evidence from large-scale longitudinal studies is scarce. We leveraged data from the US Health and Retirement Study (n = 7444; mean age: 67.7 ± 9.7 years). Our primary analysis calculated three ratio metrics to quantify T-cell immunosenescence: the CD4:CD8 ratio, CD4 + EMRA: Naïve and CD8 + EMRA: Naïve...

No abstract

Biguanides, including metformin, the world's most prescribed oral hypoglycemic, extend health span and lifespan in vertebrates and invertebrates. Given the widespread use and apparent safety of metformin, it is assumed that its effects are not associated with toxicity, except when in marked excess. Here, we determine that accumulation of damaging reducing equivalents is an unanticipated toxicity associated with biguanides, defense against which requires post-transcriptional protection of de novo...

Posttraumatic stress disorder (PTSD) exhibits high rates of comorbidity with Substance Use Disorders (SUDs) and Traumatic Brain Injury (TBI), especially in older adults who are subject to the effects of psychological trauma due to combat exposure, health-related and psychosocial outcomes, and aging. This narrative review explores the associations between PTSD and comorbidities of psychoactive substance abuse and traumatic brain injuries on the incidence of Alzheimer's disease (AD) in veterans...

CONCLUSIONS: Physical activity levels were non-linearly associated with the risk of intrinsic capacity impairment, with moderate levels being associated with a lower risk. This study further identified marked heterogeneity in the associations between physical activity and different intrinsic capacity domains, suggesting that the benefits are not uniform across functional domains. These findings highlight the importance of maintaining an appropriate level of physical activity and support the...

CONCLUSION: This study indicates that phytoestrogens are associated with sarcopenia, and the direction of this association depends on the specific type of estrogen. The findings reveal that O-DMA, Enterolactone, and total phytoestrogens possess a preventive effect against sarcopenia in female and it also reveal that Daidzein possess a preventive effect against sarcopenia in male.

Behçet's syndrome (BS) is a chronic multisystemic inflammatory disorder with a heterogeneous clinical course. A severe subset with central nervous system involvement (neuro-Behçet's syndrome, NBS) carries substantial morbidity. While disease activity often decreases with age, the long-term neurological and cognitive outcomes remain poorly defined. Emerging evidence indicates that vascular insufficiency, chronic inflammation, and central nervous system involvement may contribute to cognitive...

The antagonistic pleiotropy theory of aging predicts genetic trade-offs between early-life and late-life fitness. However, empirical evidence for such trade-offs in vertebrates remains scarce, particularly from causal genetic experiments. Here, combining genetic perturbation with longitudinal phenotyping in the turquoise killifish (Nothobranchius furzeri), we identify vestigial-like 3 (vgll3), previously linked by GWAS to age at maturity in humans and male Atlantic salmon, as a gene with...

No abstract

Excessive artificial light at night (ALAN) disrupts circadian rhythms and may accelerate ocular aging; however, personal objective dosimetry data linking evening light exposure to specific age-related eye diseases (AREDs) remain sparse. The objective of the study is to determine whether personal high-intensity light exposure during the evening transition window (20:00-23:30) is associated with the risk of incident age-related macular degeneration (AMD), cataracts, and glaucoma. This prospective...

Time-restricted feeding (TRF) aligned with an organism's circadian rhythm has been shown to improve health, but its long-term effects on healthspan and lifespan in mammals, especially under standard dietary conditions that do not promote obesity, remain unclear. Here, we examined the impact of 12-h and 8-h nightly TRF windows in 264 male and 264 female C57BL/6 J mice fed regular chow. TRF improved multiple health measures, including behavioral rhythmicity, body weight and composition, frailty,...

The DREAM complex has emerged as a central repressor of DNA repair, raising questions as to whether such repression exerts long-term effects on human health. Here we establish that DREAM-associated activity significantly impacts lifetime somatic mutation burden, and that such effects are linked to altered lifespan and age-related disease pathology. First, joint profiling of DREAM-associated activity (quantified from the expression of genes transcriptionally repressed by DREAM) and somatic...

Glucagon-like peptide-1 receptor agonists, including long-acting semaglutide, are transformative anti-obesity therapies. However, emerging evidence indicates that weight loss may come at the expense of skeletal muscle mass, a tissue essential for mobility, metabolic regulation, and overall health. Here, we show that inhibition of the gerozyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin-degrading enzyme that increases with injury and aging, improves muscle repair and strength...

Trade-offs between lifespan and reproduction are a central theme in evolution and ecology, often attributed to physiological constraints on the allocation of limiting resources. However, recent work suggests such trade-offs may depend on macro- and micronutritional context. We examined how macronutrient balance and cholesterol availability shape lifespan and reproductive performance in male Drosophila melanogaster, explicitly testing both unmated males and those permitted to mate freely...