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An experimental GLP-1 pill helped people with obesity or overweight lose as much as 12.1% of their body weight in just 36 weeks. Unlike injectable drugs such as Wegovy and Ozempic, aleniglipron is a small molecule that can be taken once daily with or without food and could potentially be produced more easily at scale.

Very high levels of the inherited cholesterol-related particle Lp(a) were linked to a greater risk of major cardiovascular events, particularly stroke and cardiovascular death, in a study of more than 20,000 people. Since elevated Lp(a) often flies completely under the radar, a simple blood test could uncover hidden heart risk that standard cholesterol testing may miss.

As climate change heats up the continent, experts say countries must shift focus toward preventing fires, rather than just suppressing them

Mutations in leucine-rich repeat kinase 2 (LRRK2) are the second most common cause of autosomal-dominant Parkinson's disease (PD), and increased LRRK2 kinase activity is also observed in idiopathic PD, making LRRK2 a major actionable therapeutic target. LRRK2 is a 286-kDa multidomain enzyme containing a Ras-like GTPase (ROC) and a kinase domain. Using cryo-electron microscopy (cryo-EM), biochemical reconstitution, and cell-based assays, we show that the ROC GTPase governs switching between...

Deficiencies in glucocerebrosidase (GCase) are associated with Parkinson's disease (PD). The mechanistic basis of this association is being intensively investigated, and new treatments are being developed aiming to boost brain GCase activity in patients. Despite the importance of GCase in PD, studies are hampered by the continued reliance on weak and non-selective inhibitors like conduritol B epoxide. Here, we report easily prepared and selective irreversible inhibitors and complementary...

Neurons accumulate somatic mutations with age, but how mutation processes vary among neuronal types remains unclear. Characterizing this variability may elucidate the role of genome integrity in brain function and disease and reveal determinants of mutation rates and patterns. Using high-fidelity duplex DNA sequencing, we profiled somatic mutations across the lifespan in human cerebellar Purkinje and granule neurons, which differ markedly in size and physiology. Surprisingly, they exhibited...

Dioscin, a naturally occurring steroidal saponin isolated from various kinds of herbs with pleiotropic pharmacological properties, remains mechanistically undefined regarding its mammalian aging modulation. This study discovered that dioscin extended the lifespan of Caenorhabditis elegans. Concurrently, dioscin improved the motor function of C. elegans and reduced age pigment accumulation, while having no effect on the reproductive performance of the C. elegans. By pathway screening, we...

Cardiac aging is a central biological process underlying most cardiovascular diseases. Lysosomes, once regarded as terminal degradative compartments, are now recognized as dynamic metabolic and signaling hubs whose dysfunction has profound consequences for the aging heart. Human lysosomal storage disorders provide compelling evidence that isolated lysosomal defects are sufficient to cause early cardiomyopathy, underscoring the myocardium's exceptional dependence on sustained lysosomal...

Parkinson's disease (PD) is an age-associated neurodegenerative disorder in which affective non-motor symptoms substantially contribute to disease burden, yet their neurobiological basis remains incompletely understood. We investigated region-specific alterations of corticotropin-releasing hormone (CRH) family neuropeptides in a rotenone-induced rat model of PD and evaluated the effects of combined dopaminergic (benserazide/L-DOPA) and antidepressant (fluoxetine) treatment. Motor performance,...

Frailty syndrome, characterized by diminished physiological reserves and heightened vulnerability to adverse health outcomes, is a major concern in aging populations. Physical activity (PA) is a proven intervention for frailty syndrome prevention and treatment, but evidence on how different intensities, durations, and doses of PA affect frailty and survival in China populations remains limited. We analyzed data from the China Health and Retirement Longitudinal Study (CHARLS), a nationally...

Identifying biological and clinical signals that consistently predict physical resilience, defined as one's ability to maintain or regain function following a health stressor, is essential for advancing precision approaches to aging and recovery. High-dimensional datasets hold tremendous promise but pose analytic challenges due to correlation, distributed signals, instability, and sensitivity to analytic choices. The complexity of these data requires strategies that prioritize transparency and...

CONCLUSIONS: IC impairments, severity, and patterns independently predicted fall-related ED visits. Integrating ICOPE screening into primary care may enhance fall prevention strategies.

No abstract

Knee osteoarthritis (KOA) is a leading cause of late-life pain, mobility loss, and disability, and is increasingly recognized as a phenotype-dependent manifestation of joint aging rather than a purely mechanical disorder. Cellular senescence, inflammaging, mitochondrial dysfunction, synovial inflammation, vascular remodeling, and impaired repair capacity converge to shape KOA symptoms and progression. This narrative review synthesizes evidence on conservative and minimally invasive KOA therapies...

Parkinson's disease is characterized by dopaminergic neuron loss and accumulation of α-synuclein aggregates in the brain. G51D α-synuclein knock-in mice provide a genetically and clinically relevant model of disease, exhibiting early olfactory deficits, age-dependent motor impairment, and progressive phospho-α-synuclein accumulation. In multiple Parkinson's disease models, striatal cholinergic and parvalbumin interneurons, as well as astrocytes, lose primary cilia and the neurotrophic signaling...

Successful repair after brain injury requires a chain of events, including the generation, migration, and successful integration of adult-born neurons into preexisting circuits. In mammals, the capacity for neuronal regeneration is extremely limited and further declines with age, constraining recovery. Regeneration-competent vertebrates offer a unique opportunity to uncover mechanistic principles of seamless brain repair. We here introduce the African turquoise killifish, a naturally short-lived...

Microglia, the resident macrophages of the central nervous system (CNS), are key players in maintaining brain and spinal cord homeostasis and protecting the CNS from damage and disease. During aging, the brain undergoes profound changes-including chronic low-grade inflammation, synaptic dysfunction, and increased vulnerability to neurodegenerative diseases-all of which are closely related to alterations in microglial function. One emerging theme is that microglial metabolism is a crucial...

Microglia, the resident macrophages of the central nervous system (CNS), are key players in maintaining brain and spinal cord homeostasis and protecting the CNS from damage and disease. During aging, the brain undergoes profound changes-including chronic low-grade inflammation, synaptic dysfunction, and increased vulnerability to neurodegenerative diseases-all of which are closely related to alterations in microglial function. One emerging theme is that microglial metabolism is a crucial...

Telomere length (TL) is a well-established biomarker of biological ageing, sensitive to cumulative physiological and psychosocial stress. This review synthesises current evidence on how pregnancy, postpartum stressors, and reproductive history shape maternal biological ageing, integrating findings from telomere biology and emerging epigenetic ageing measures. Pregnancy represents a period of substantial metabolic, hormonal, and immunological demand and is increasingly conceptualised as a...

Chronic subdural hematoma (CSDH) is among the commonest cranial neurosurgical conditions of older adults and is projected, on the basis of incidence modeling, to become the most common cranial neurosurgical condition in adults by 2030. Despite this clinical centrality, CSDH has not been formally examined through the conceptual lens of geroscience. This minireview reframes CSDH as a geroscience disease by mapping its pathogenesis onto the twelve hallmarks of aging articulated by López-Otín and...