Aging & Longevity

Aging reshapes neurotransmitter systems through nonlinear and region-specific shifts that alter excitatory-inhibitory balance, weaken metabolic coupling, and destabilize large-scale neural networks. PET, MRS, molecular MRI, and optical imaging quantify elements of these trajectories, but modality-specific artifacts, cross-site variability, and limited spatial or temporal resolution fragment mechanistic interpretation. Artificial intelligence now enables the integration of these heterogeneous...

Impaired oligodendrocyte precursor cell (OPC) differentiation limits myelin renewal in aging and contributes to multiple sclerosis (MS) progression. How aging drives OPC deficits remains incompletely understood. We find dysregulation of genes associated with the circadian clock, including Bmal1, and metabolism in aged compared with young OPCs. Targeted loss of Bmal1 in OPCs drives metabolic dysfunction, leading to cellular senescence and impaired dynamics. OPC proliferation and differentiation...

CONCLUSION: AI-based CT volumetry identifies low skeletal muscle volume as an independent predictor of long-term mortality after TAVI. Muscle quantity, rather than muscle quality, appears to be the dominant prognostic determinant. AI-driven body composition analysis may serve as an imaging biomarker of biological aging and reduced physiological reserve in older adults undergoing TAVI.

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De novo mutations (DNMs) are an important source of congenital diseases. With delayed parenthood and assisted reproductive technology (ART) use increasing, it is essential to elucidate how these reproductive factors influence DNMs and whether resulting mutations influence offspring health. Here we performed whole-genome sequencing of 24,030 individuals from 7,851 parent-offspring families, identifying 390,924 de novo single-nucleotide variants (dnSNVs). Paternal and maternal aging exhibited...

Dementia arises from multifactorial neurodegenerative processes, with growing evidence implicating blood-brain barrier dysfunction, neuroinflammation, and vascular injury as contributors to progressive brain tissue damage. Because decline in white matter microstructural integrity is a prominent feature of brain aging, biomarkers that capture this process may improve dementia risk stratification beyond conventional clinical factors. Fractional anisotropy (FA), derived from diffusion tensor...

White matter integrity is a sensitive marker of cerebrovascular health and aging. Physical activity may promote white matter health, but previous studies were limited by self-reported activity and small sample sizes. We examined the association between accelerometer-based physical activity and novel indices of white matter integrity while identifying potential mediators. We analyzed cross-sectional baseline data from 4188 participants (58% women, mean age: 55.4 years) of the Rhineland Study, a...

CONCLUSION: GTC in older trauma patients helps identify delirium and potentially reduces the need for antipsychotics and improves mortality. A randomized controlled trial is needed to verify these findings.

Recent studies debate whether caldera-forming silicic magma is primarily stored in a crystal-poor, eruptible state for >100,000 years (kyr) ("warm storage") or exists as a crystal-rich "mush" with defrosting events causing brief periods (<1 kyr) of eruptibility ("cold storage"). To address this, we examined Aira Caldera (Japan), where the 400-cubic kilometer Aira-Tanzawa (AT) eruption (30,000 years ago) was preceded by three smaller eruptions over 3.5 kyr. All eruptions consist of roughly...

To date, the identity and maintenance of postnatal thymic epithelial progenitor cells (TEPCs) remain unclear, as does the persistence of bipotent TEPCs after birth or whether lineage-restricted progenitors independently maintain separate TEC compartments. Using an inducible lineage-tracing system based on expression of the thymoproteasomal protein β5t, which is expressed in embryonic and a subset of postnatal TEPCs, we explored the early dynamics of the relationships between thymic epithelial...

Chronic oxidative stress has long been implicated in renal pathologies, but whether sustained oxidative damage primarily promotes chronic kidney disease (CKD) or tumorigenesis remains unclear. To address this question, we investigated the long-term effects of oxidative stress on human embryonic kidney (HEK293T) cells chronically exposed to a low dose of hydrogen peroxide (H(2)O(2), 50 μM H(2)O(2)) for 9 months, generating two adapted lines, 50R30 and 50R45. These cells exhibited enhanced...

Aging is a multifactorial process affects different tissues and organs and is modulated by genetic and environmental factors. In aging, the frequency of DNA repair errors and genomic instability are augmented. Depletion of endogenous antioxidant capacity during aging promotes the development of oxidative stress which triggers oxidative stress-induced DNA injury. Brain aging is manifested by cognitive impairment and memory disorders. Development of neuronal senescence is the major pathway in the...

Cognitive aging is shaped by genetic variation, environmental factors, and health-related conditions. Until now, it is largely unclear why some individuals maintain their cognitive function, and others show progressive cognitive decline. This study uncovered determinants of distinct cognitive aging trajectories in the older population. To approach the inter-individual variability in cognitive aging, we clustered n = 696 dementia-free individuals from the prospective TREND study based on their...

It has been hypothesized that age‑related declines in skeletal muscle and vascular function in females may be partly estrogen‑dependent. This study investigated skeletal muscle protein expression of estrogen receptor α (ERα), estrogen receptor β (ERβ), and G protein-coupled estrogen receptor 1 (GPER1), and their association with proteins involved in redox regulation and vascular function, in relation to age, menopausal status, and lifelong physical activity. Skeletal muscle biopsies were...

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Microenvironment remodelling impacts tumour growth and metastasis, but whether remodelling promotes pre-malignant clonal fitness remains unknown. Here, using single-cell RNA-sequencing of the bone-marrow microenvironment in a mouse model of DNMT3A-mutant clonal haematopoiesis (CH), we identify mesenchymal stromal cells (MSCs) in a molecular state of cellular senescence. Elevated bone-marrow MSC senescence is also observed in humans with CH driven by several common somatic mutations. MSC...

Haemoglobin is a ferrous iron (Fe^(2+))-containing intracellular protein that is crucial for multiple homeostatic functions, including transport of oxygen and carbon dioxide, acid-base buffering and cellular signalling through nitric oxide oxidation and nitrite reduction. When erythrocyte membranes are disrupted, a process known as haemolysis that is caused by either disease or an exogenous stressor, haemoglobin is liberated into the plasma. This plasma free haemoglobin is highly pathogenic,...

CONCLUSION: The current evidence does not establish a definitive APOE ε4-specific preventive effect of PA. Future studies may be most informative if they target earlier-stage, low-active, or metabolically at-risk APOE ε4 carriers using objective PA measures and proximal vascular, metabolic, imaging, or blood-based biomarker outcomes.

Classical evolutionary theories of aging, including antagonistic pleiotropy (AP) and the disposable soma theory (DST), explain why aging exists but are often applied without considering how sex-specific reproductive strategies shape the forces of natural selection on survival. They do not explain why females consistently outlive males across taxa, despite their greater reproductive investment, or why in some contexts, such as eusocial queens, extraordinary fecundity is coupled with exceptional...

Hyperphosphorylation and aggregation of tau are pathological hallmarks of tauopathies. Mitochondrial dysfunction is also a common feature of tauopathies. The mechanistic link between tau abnormalities and mitochondrial dysfunction and its relationship to the physiological function of tau, however, is unclear. Here, we demonstrate that tau regulates mitochondrial reverse electron transport (RET), which produces excess reactive oxygen species (ROS), reduces the NAD^(+)/NADH ratio, and is activated...