Synapses in the outer retina undergo age-related functional decline, but the molecular mechanisms are unknown. The authors showed that synaptic changes in ageing mouse retinas are linked to reduced activity of the serine/threonine kinase LKB1, which in turn reduced phosphorylation of its substrate AMPK. Mice lacking AMPK or LKB1 had synaptic alterations similar to those found in aged mice, including loss of rod photoreceptors and axonal retraction. These defects could be reversed by pharmacological activation of AMPK, which might have therapeutic potential in the treatment of age-related alterations in retinal physiology.