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Population aging has accelerated globally, making successful aging a key public health priority. Zhuang and Gao address the prospective association between cumulative average grip strength and successful aging using three international cohorts. While their multi-cohort design offers valuable cross-population insights, several methodological choices warrant consideration. Grip strength may not fully capture functional determinants of successful aging. Self-reported chronic disease introduces...

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Pleiotrophin (PTN) is a heparin-binding growth factor that plays a pivotal role in neurodevelopment, neuroplasticity, and neuroinflammation. PTN signals through a multi-receptor network involving protein tyrosine phosphatase receptor type ζ (PTPRZ1), syndecans (particularly syndecan-3), integrins, nucleolin, and neuropilin-1. Anaplastic lymphoma kinase (ALK) has also been functionally linked to PTN signaling, although whether PTN directly binds and activates it remains debated. This review...

Attention deficit-hyperactivity disorder (ADHD) is a medical condition that is present in approximately 2.5% of adults worldwide and manifests in a variety of different ways across the lifespan. Adults with ADHD often have coexisting psychiatric disorders such as anxiety, mood, sleep, substance use, and personality disorders and are at increased risk for coexisting somatic conditions such as obesity, cardiovascular and cerebrovascular disease, type 1 and type 2 diabetes, and immune and...

Senescent cells develop a persistent inflammatory signature with broad consequences for tissue function and disease. Martini et al.¹ show that mitochondrial citrate metabolism drives inflammation through a pathway that acts independently of mitochondrial DNA-driven immune signaling yet cooperates with it to amplify the inflammatory response.

Loss of skeletal muscle mass is a major driver of frailty and disability, yet how systemic metabolic cues protect muscle integrity remains unclear. We identify Serpina3n, an adipose-derived adipokine, as a key mediator of the protective effects of nicotinamide adenine dinucleotide (NAD^(+)) supplementation against muscle atrophy. Elevation of NAD^(+) in adipose tissue activates signal transducer and activator of transcription (STAT)1-dependent transcription of Serpina3n, leading to its systemic...

Population ageing has increased the burden of cardiovascular disease, cognitive decline and frailty in older adults. These conditions are often studied separately, yet increasing evidence suggests that the ageing heart, vasculature and brain are biologically interconnected. Using a hybrid design that combines a systematic literature search with narrative synthesis, this review summarizes current knowledge on heart-brain co-ageing, with emphasis on phenotypic heterogeneity, molecular mechanisms...

Immune aging comprises heterogeneous changes in hematopoietic output, immune-cell function, inflammatory regulation, and tissue-specific immune states. In parallel, the gut microbiome undergoes ecological and functional remodeling across the bacteriome, mycobiome, virome, and archaeome, but these changes do not define a single "aged microbiome" and vary with host health, frailty, diet, medication exposure, and environmental context. Here, we examine how multikingdom gut microbiome remodeling...

Neuroimaging-derived brain age has emerged as an intuitive marker of brain health and cognitive longevity. The difference between brain age and chronological age, termed brain-predicted age difference (brain-PAD), quantifies deviation from normative brain ageing and may help evaluate whether interventions could attenuate brain ageing trajectories. This review synthesizes the methodological foundations of brain age estimation, factors linked to brain-PAD across healthy ageing and disease,...

CONCLUSION: FGF-19 concentration showed exploratory negative associations with functional capacity. FGF-19 was not associated with the change in functional capacity following the exercise intervention.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no effective cure, characterized by the cerebral parenchymal and vascular accumulation of aggregated amyloid-β (Aβ) and hyperphosphorylated tau. Cerebrovascular and mitochondria dysfunction are early causal events in the progression of AD. Previous studies support that inhibiting carbonic anhydrases (CAs) may prevent mitochondrial and cerebrovascular dysfunction in AD models. Here, we selectively target the mitochondrial...

Microglial dysfunction is increasingly implicated in Alzheimer's disease (AD) pathogenesis, with loss-of-function variants in the microglial receptor TREM2 as major risk factors for late-onset AD. We report VG-3927, an oral, CNS-penetrant small-molecule TREM2 agonist that engages the transmembrane domains of TREM2 and its adaptor DAP12 to promote higher-order receptor complex formation and downstream signaling. VG-3927 and tool compound VG-3909 exhibited (sub)nanomolar potency, cooperated with...

As life expectancy increases globally, ageing has emerged as the main risk factor driving the increasing burden of neurological disorders. Although advances have been made in understanding their pathogenesis, current therapies remain largely symptomatic and do not prevent disease progression. There is a growing body of evidence that these disorders share common molecular mechanisms, including oxidative stress, mitochondrial dysfunction, neuroinflammation, impaired autophagy, ferroptosis, and...

Physical performance declines with age, but its association with circulating neurodegeneration biomarkers remains unclear. Blood biomarkers including NT1, NfL, oAβ, and pTau217 may reflect early neurodegenerative changes linked to physical performance decline. Evidence linking these biomarkers to physical performance is limited. We analyzed older adults in the COSMOS Clinic substudy with baseline and two-year follow-up assessments of plasma NT1, NfL, and oAβ and a single assessment of pTau217....

The slow kinetics of sulfur cathodes caused by the high energy barriers of Li^(+) desolvation stem primarily from the structure of the inner Helmholtz plane (IHP). Herein, a synergistic strategy combining electrochemical tandem catalysis with spatial nanoconfinement is proposed to regulate the Li(solvent)(x)^(+) dynamics. As a proof-of-concept, the porous covalent organic framework (denoted as TPBD) decorated MXene is in situ constructed, acting as a tandem kinetic promoter. The theoretical...

Ozone has been viewed as the principal oxidant of skin oils and other unsaturated surface films, but their fate under realistic indoor conditions remains poorly constrained. Here, we use squalene (SQ), a major component of skin lipids, to investigate the dominant oxidation pathways in occupied indoor environments and laboratory flow reactors. With exposure to indoor air, SQ decay and reactive oxygen species (ROS) formation accelerated over time, consistent with autoxidation. Laboratory...

Aging is characterized by progressive functional decline, yet metabolomic signatures across the human life span remain incompletely defined. Here, we profiled plasma metabolomes from 18,476 participants aged 1 to 96 years across six centers in China using nano-assisted laser desorption/ionization mass spectrometry (LDI-MS) and identified 56 representative age-associated metabolites. In a healthy cohort, we developed a stacking ensemble model to estimate metabolomic age and quantified metabolomic...

CONCLUSION: The temporal scalp θ/α ratio and right precuneus gray matter volume are promising candidate non-invasive auxiliary biomarkers for Aβ pathological stratification in aMCI, rather than validated clinical diagnostic biomarkers. The multimodal model provides supplementary subtyping value within this single-center cohort, while external multicenter validation is mandatory before clinical application. This cross-sectional dataset cannot support prediction of longitudinal progression to AD...

Autistic adults experience lifelong motor differences and may have increased vulnerability to parkinsonism, yet behavioral and neuroanatomical correlates of motor challenges across adulthood remain poorly understood. We examined cross-sectional behavioral and motor-related brain region morphology in autistic (n = 123) and non-autistic (n = 102) adults aged 18-71 years using the Parkinsonism Screening Questionnaire (PSQ), Adult Repetitive Behavior Questionnaire-2 (RBQ-2A), finger tapping, and...