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DNA-protein crosslinks (DPCs) are one of the most complex and deleterious forms of DNA damage. DPCs arise from the stabilization of covalent enzyme-DNA intermediates, such as topoisomerase cleavage complexes, or from exposure to bifunctional crosslinking agents, and they differ in protein identity, DNA context and chemical linkage. Because of their bulky nature, DPCs obstruct essential chromatin processes such as DNA replication and transcription, making their timely removal by dedicated DPC...

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Terrestrial ecosystems are changing rapidly under global nutrient enrichment, yet how canopy nutrients balance shapes the seasonal end of photosynthesis, a critical control on ecosystem carbon cycling, remains unclear. Rising anthropogenic nitrogen inputs are shifting many ecosystems towards relative phosphorus limitation, with uncertain consequences for autumn phenology. Here, we combined airborne imaging spectroscopy with remotely sensed phenology to test whether canopy nutrient ratios predict...

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is promoted by atrial fibrosis, a form of structural remodelling for which effective therapies are lacking. MicroRNA-31-5p (miR-31-5p), an aging-associated, atrial-enriched microRNA, has been linked to AF, but its role in atrial fibrosis is unknown. Here we show that atrial fibroblasts from patients with persistent AF exhibit increased miR-31-5p expression and reduced expression of the calcitonin receptor (CTR, encoded...

Tree shrews are small mammals closely related to primates, which originate in Southeast Asia. In several aspects of their morphology and physiology, tree shrews more closely resemble humans than rodents. For example, the development of their visual system parallels that of humans, making them a desirable model species for pre-clinical research. Despite the use of tree shrews in research for over 50 years, little is known about the basic demography of tree shrews. No detailed lifespan studies are...

CONCLUSIONS: Adding modest dairy product intake to home-based resistance training did not provide additional overall benefits compared to exercise alone. However, exploratory findings suggest that baseline dairy consumption may influence the responsiveness of older adults to combined nutrition and exercise interventions.

CONCLUSION: Higher insulin resistance is a significant modifiable factor for cognitive impairment, specifically in women aged ≥65 years. These exploratory findings suggest potential sex-related differences in the metabolic-cognitive association, underscoring the importance of sex-specific metabolic management starting from midlife to help preserve cognitive health in later life.

A promising new study suggests that more than half of younger adults with type 2 diabetes could achieve remission in just six months through a combination of a low-calorie diet and structured exercise. Researchers found that 54% of participants under age 45 who followed an intensive diet and exercise program achieved remission, compared with just 4% receiving usual care.

Scientists have uncovered hidden aggressive cancer cells in children whose tumors were previously considered lower risk, revealing why some cases of rhabdomyosarcoma become unexpectedly deadly. The discovery could help doctors identify dangerous tumors earlier and develop personalized treatments that improve survival while reducing unnecessary chemotherapy.

The deacetylase SIRT1 is a critical regulator of cellular senescence, and the excessive accumulation of senescent cells can further drive the onset of organismal aging. SIRT1 activity is tightly governed by posttranslational modifications, including ubiquitination. While ubiquitination has been well documented to control SIRT1 protein stability, the precise regulatory pathway underlying SIRT1 activity remains poorly understood. Here, we identify the deubiquitinase USP25 as a central regulator of...

A growing body of evidence implicates the menopausal transition as a neurobiological inflection point in women's brain aging and Alzheimer's disease (AD) vulnerability. Menopause is a midlife neuroendocrine transition characterized by a decline in sex steroid hormones and widespread systemic effects. The brain is not a passive recipient of ovarian hormones but an active endocrine-sensing organ. Menopause, however, does not act in isolation: the ovarian-brain axis is established embryonically,...

Oxidative stress and lipid peroxidation are increasingly recognized as age-related drivers of neurodegeneration, with Parkinson's disease (PD) representing a condition of heightened vulnerability. Among lipid peroxidation products, reactive aldehydes including 4-hydroxy-2-nonenal, malondialdehyde, acrolein, 4-hydroxy-2-hexenal, and crotonaldehyde have emerged not only as biomarkers of oxidative damage, but also as active mediators of neuronal dysfunction. Owing to their electrophilic nature,...

Cryogenic electron microscopy has revealed endpoint structures of ex vivo amyloid filaments, but how amyloids assemble and evolve in living organisms-and how these transitions affect physiology-remains poorly understood. Here, we map the age-dependent structural landscape of Orb2 amyloid, a synaptic translation regulator required for long-term memory, across the adult lifespan of Drosophila melanogaster. By determining multiple Orb2 amyloid structures, we uncover a dynamic, age-linked...

A growing body of evidence implicates the menopausal transition as a neurobiological inflection point in women's brain aging and Alzheimer's disease (AD) vulnerability. Menopause is a midlife neuroendocrine transition characterized by a decline in sex steroid hormones and widespread systemic effects. The brain is not a passive recipient of ovarian hormones but an active endocrine-sensing organ. Menopause, however, does not act in isolation: the ovarian-brain axis is established embryonically,...

Oxidative stress and lipid peroxidation are increasingly recognized as age-related drivers of neurodegeneration, with Parkinson's disease (PD) representing a condition of heightened vulnerability. Among lipid peroxidation products, reactive aldehydes including 4-hydroxy-2-nonenal, malondialdehyde, acrolein, 4-hydroxy-2-hexenal, and crotonaldehyde have emerged not only as biomarkers of oxidative damage, but also as active mediators of neuronal dysfunction. Owing to their electrophilic nature,...

CONCLUSION: This study provides the first multivariate genomic characterization of vascular ageing using Genomic SEM, uncovering loci newly implicated in vascular ageing, convergent putative causal genes, and cellular substrates that link vascular biology to systemic ageing and may inform precision prevention of age-related vascular disorders.

Chaperone-mediated autophagy (CMA), regulated by its lysosomal receptor LAMP2A, is a key pathway for αSynuclein (αSyn) clearance and a direct target of αSyn-related neurotoxicity. Rodent studies show that LAMP2A enhancement reverses neurodegeneration, whereas its deficiency accelerates pathology. To test translational relevance, we examined whether increasing LAMP2A expression in nonhuman primates could mitigate α-synucleinopathy induced by injections of Parkinson's disease patient-derived Lewy...

Cross-modal associative memory impairment is one of the earliest cognitive markers of neurodegenerative disorders and may be particularly sensitive to the detection of Mild Cognitive Impairment (MCI). The Italian Face-Name Association Test (ItFNAT) assesses face-name associative memory through immediate recall (IR), delayed free (DFR), and total recall (DTR), and qualitative indices. This study provides psychometric properties, discriminative capacity, and diagnostic accuracy in older adults. A...

Cells exhibit innate reparative communication, enabling the exchange of bioactive molecules and, in some cases, entire organelles. Harnessing this endogenous process of intercellular organelle transfer represents an emerging therapeutic paradigm for restoring cellular function in diseases driven by organelle dysfunction. Mitochondrial transfer has gained prominence for its ability to restore bioenergetic capacity, mitigate oxidative stress, and rescue metabolic function in cells with impaired...

CONCLUSION: Cognitive advantages observed in women in midlife did not translate into lower dementia risk. Further research incorporating biological, psychosocial and life-course factors, as well as the timing and heterogeneity of underlying disease processes, is needed to better understand sex differences in cognitive ageing and dementia.