A transient pulse of neuronal ATF4 installs a durable non-autonomous programme promoting healthy ageing

Transient neuronal ATF4 gain-of-function in early adulthood extends lifespan in Drosophila melanogaster, slowing locomotor decline and increasing starvation resistance in old age.

• Why it matters: Early-life activation of the ATF4-linked integrated stress response may shape long-term health, but the timing, duration, and tissue requirements for these effects are unclear.
• What they did: Using inducible, reversible ATF4 gain-of-function, the study tested how activation timing and tissue specificity alter ageing, including multi-organ transcriptomics and tissue-restricted induction.
• The result: Neuron-only ATF4 activation produced a lasting non-autonomous imprint on the fat body in old age, including heterochromatin gene induction, reduced transposable element expression, and increased mitochondrial respiratory capacity.

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