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Fisetin Attenuates D-Gal-Induced Ovarian Aging by Modulating Mitophagy via the AMPK/mTOR Pathway

This study aimed to explore the alleviating effects of fisetin, a polyphenolic flavonoid, on ovarian dysfunction in a D-galactose (D-gal)-induced aging mouse model, as well as the underlying mechanisms, using both in vivo and in vitro experiments. Mice were subcutaneously injected with D-gal (100 mg/kg/day) for 60 days to establish the ovarian aging model; during the final 30 days, fisetin (10, 20, 30 mg/kg/day) was given orally. In addition, a senescent model of granulosa cell (GC) was established using D-gal and treated with fisetin. Fisetin supplementation improved ovarian endocrine function and reproductive capacity in aging mice, as reflected by regularized estrous cycles, elevated estradiol levels, and increased embryo numbers.

Decoding intended speech with an intracortical brain-computer interface in a person with long-standing anarthria and locked-in syndrome

This study aimed to explore the alleviating effects of fisetin, a polyphenolic flavonoid, on ovarian dysfunction in a D-galactose (D-gal)-induced aging mouse model, as well as the underlying mechanisms, using both in vivo and in vitro experiments. Mice were subcutaneously injected with D-gal (100 mg/kg/day) for 60 days to establish the ovarian aging model; during the final 30 days, fisetin (10, 20, 30 mg/kg/day) was given orally. In addition, a senescent model of granulosa cell (GC) was established using D-gal and treated with fisetin. Fisetin supplementation improved ovarian endocrine function and reproductive capacity in aging mice, as reflected by regularized estrous cycles, elevated estradiol levels, and increased embryo numbers. Furthermore, fisetin reduced the number of atretic follicles and the extent of ovarian fibrosis and senescence, while simultaneously restoring the proliferation-apoptosis balance in follicular GCs, as well as alleviating oxidative stress. RNA-sequencing revealed that AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) signaling and mitophagy were involved in the protective effects of fisetin against ovarian aging. Consistently, fisetin treatment promoted mitophagy, accompanied by AMPK/mTOR activation in ovarian tissues and GCs following D-gal exposure. Inhibition of AMPK attenuated the effect of fisetin on mitophagy. Additionally, blockage of mitophagy also reversed the beneficial effects of fisetin on mitochondrial injury, oxidative stress, cell cycle arrest, and cellular senescence in D-gal-induced senescent GCs. These findings indicate that fisetin prevents ovarian aging by suppressing follicular GC oxidative damage and ameliorating cell cycle arrest via activation of AMPK/mTOR-mediated mitophagy, thereby preserving female fertility.

Sleep Duration Linked to Accelerated Aging

The relationship between sleep and disease suggests that there exists a connection between the brain and the body that extends beyond merely influencing the brain itself.

Among brain-related disorders, short sleep was significantly associated with depressive episodes and anxiety disorders, as seen in other studies of sleep and mental health. Short sleep was also associated with obesity, type 2 diabetes, hypertension, ischemic heart disease, and heart arrhythmias.

Short and long sleep were associated with chronic obstructive pulmonary disease, asthma, and a cluster of digestive disorders, including gastritis and gastroesophageal reflux disease.

Enhancing Non-small Cell Lung Cancer Susceptibility to Anti-PD-1/PD-L1 Therapy through PD-L1 Ligand–Ir(III) Complex Conjugates

Immunotherapy targeting programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) has transformed the management of several types of cancers, including non-oncogene-addicted non-small cell lung cancer (NSCLC) [1], although its efficacy remains limited by resistance mechanisms and constraints inherent to monoclonal antibodies [1]. To overcome these drawbacks, small-molecule PD-L1 inhibitors have been developed, and we previously contributed by identifying the nanomolar triazine-based ligand Tr-10 [2]. In parallel, combinatorial strategies aimed at improving the efficacy of anti-PD-1/PD-L1 immunotherapy have gained increasing attention. Notably, platinum-based chemotherapy combined with immune checkpoint inhibitors is recommended as a first-line treatment for advanced NSCLC with PD-L1 expression <50% [3]. Here, we investigated a novel combination involving our anti-PD-L1, Tr-10 [2], and a bis(phenyl-pyridine)iridium(III) complex, Ir-2 (Fig. 1A) [4]. Iridium (Ir) complexes, unlike platinum drugs, are chemically inert and induce endoplasmic reticulum (ER) stress and overproduction of reactive oxygen species (ROS) [5,6], both culminating in damage-associated molecular pattern (DAMP) release and immunogenic cell death (ICD). Moreover, their photophysical properties enable PD-L1-targeted bioimaging when coupled with PD-L1 ligands (Fig. S1) [7].

Immunosenescence and Inflammaging as Drivers of Neurodegeneration: Cellular Mechanisms, Neuroimmune Crosstalk, and Therapeutic Implications

Aging is accompanied by profound alterations in immune function, termed immunosenescence, and by a chronic, low-grade inflammatory state known as inflammaging. These processes are increasingly recognized as central drivers of age-related neurodegenerative diseases, including Alzheimer’s Disease, Parkinson’s Disease, Amyotrophic Lateral Sclerosis and Multiple Sclerosis. In the central nervous system, senescent microglia and astrocytes lose their homeostatic and neuroprotective functions, while systemic immune aging and blood–brain barrier dysfunction further amplify neuroinflammation and impair protein aggregate clearance. This sustained pro-inflammatory environment promotes synaptic dysfunction, neuronal loss and cognitive decline.

Revolutionary Muscle & Fat Therapies: Future of Body Augmentation

This gene therapy company says its muscle-building treatment could last around 5 years.
The surprising part?
They believe the fastest path to market may be cosmetic enhancement using consumer demand to accelerate therapies for frailty and age-related muscle loss.

https://www.oisinbio.com/

Chronic obstructive pulmonary disease develops over decades — and we are missing the window to prevent it

Although cigarette smoking remains the main driver of COPD, e-cigarettes are also raising concerns. Vaping aerosols can contain nicotine, ultrafine particles and flavouring chemicals that may irritate the lungs and contribute to inflammation. The long-term effects are still unclear because these products are relatively new.

That matters particularly for younger people. In Great Britain, recent survey data suggest that 7% of 11-to 17-year-olds currently vape. While that does not mean they will go on to develop COPD, it does mean more young lungs are being exposed to substances whose long-term effects are not yet fully understood.

COPD is often diagnosed only after major lung damage has already occurred. Because it develops so gradually, people may dismiss early breathlessness, coughing or mucus production as a consequence of getting older, being unfit or smoking. Respiratory organisations warn that symptoms such as cough, phlegm and shortness of breath should not be treated as a normal part of ageing, while studies show that COPD remains widely underdiagnosed, including among people with respiratory symptoms.

How Intestinal Aging Encourages Harmful Bacteria

In Aging Cell, researchers have elucidated the relationship between intestinal aging and age-related changes to the gut microbiome.

Two interdependent biologies

The human gut works through the interaction of two entirely different sets of cells. The first is the body’s actual cells, including the intestinal barrier between the gut and the rest of the body, various types of ordinary immune cells, and Peyer’s patches with follicle-associated epithelium (FAE) areas that contain microfold cells (M cells), which perform crucial immunoregulatory tasks [1]. The second is the gut microbiome, the various types of bacteria that help us digest food.

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