This study shows that animal-based high-fat diets accelerate tumour growth and impair anti-tumour response to melanoma in obese mice, whereas plant-based high-fat diets do not.

Cockayne Syndrome (CS) is an autosomal recessive, progressive developmental and neurodegenerative disease. Approximately 30% of cases are caused by mutations in the ERCC8/CSA gene. Patients with CS present with cutaneous photosensitivity, growth failure, shorter life span and a progressive degeneration of the central nervous system. Loss of function mutations in CSA result in deficiencies in transcription-coupled nucleotide excision repair, regulation of RNA Pol II mediated transcription repair of oxidative DNA damage, and mitochondrial metabolism. Currently there are no available therapies for these patients. AAV gene therapy offers an opportunity to address this unmet need. We designed a new AAV vector encoding human CSA under a CBA promoter. We tested the therapeutic efficacy of this AAV9-CSA vector by neonatal ICV injection in the Csa-/-;Xpa-/- mouse model. Treatment with AAV9-CSA resulted in a significant increase in lifespan, and broad distribution of human CSA in the brain and heart. Despite clear therapeutic benefit, we also observed neuroradiological abnormalities, neuropathologic alterations including hypo-myelination, astrocytosis, microgliosis, and likely life limiting transcriptomic alterations in liver at endpoint. Nonetheless, the success of these experiments paves the way for the first in human clinical translation of a gene therapy for CS patients. ### Competing Interest Statement The authors have declared no competing interest.

Nature Metabolism, Published online: 17 March 2025; doi:10.1038/s42255-025-01237-6This broad group of authors summarizes the impact of circadian factors on metabolic biology and offers recommendations on how to account for and report biological,…

Since 1974 substantial gains in childhood survival have occurred in every global region. We estimate that EPI has provided the single greatest contribution to improved infant survival over the past 50...

Biomarkers of aging are indispensable for testing interventions. While promising, the recent focus on molecular aspects should not detract from the functional parameters for which excellent correlatio...

Dr. Francis Collins, a renowned geneticist, and former longtime director of the National Institutes of Health, is retiring from the government agency and urging “respect” for its embattled workers.

Disruption of mucin-domain glycoprotein expression and function in the endothelial glycocalyx are associated with ageing and Alzheimer’s disease, leading to dysregulated blood–brain barrier function.

Uncertain funding, government firings, and distressed universities hit vulnerable groups especially hard