Proteostasis collapse, a hallmark of aging and neurodegeneration like Alzheimer’s disease (AD), causes irreversible damage in late life. Whether late-life proteostasis capacity is developmentally programmed remains unclear, as mechanistic studies requiring lifelong tracking and molecular manipulation are challenging or impossible in long-lived species. Using C. elegans as a lifelong, genetically tractable AD model, we uncover a critical early-life window during which reducing TIP60/NuA4 acetyltransferase complex activity enduringly enhances proteostasis and extends lifespan. Mechanistically, NuA4 reduction depletes H4K16ac, triggering a compensatory, early-life-biased, XBP-1-mediated unfolded protein response (UPRER). This UPRER activation remodels endoplasmic reticulum (ER) morphology and reprograms lipid metabolism, driving selective oleic acid (OA) accumulation. Crucially, this developmentally-installed OA reservoir confers lasting resilience against proteotoxic stress, an eff

The 2024 Australian of the Year Professor Richard Scolyer has died. In his final message he urged all Australians to "pursue their dreams and passion with humility, love and compassion".

Globally, the incidence of breast cancer continues to rise; however, mortality rates are declining due to the growing effectiveness of targeted therap…