Transcriptomic Evidence Reveals the IIS-FOXO-SOD2 Axis as a Core Anti-Aging Pathway in Long-Lived Queens of...

The reproductive caste of higher termites exhibits remarkable longevity, but the mechanisms by which they manage age-related oxidative stress during lifespan extension remain insufficiently understood. This study investigated the dynamic regulation of the insulin/IGF (IIS)-FOXO axis, a key anti-aging regulatory pathway that integrates insulin signaling with downstream processes, including antioxidant defense and DNA repair, as well as the superoxide dismutase (SOD) system in female Odontotermes formosanus reproductives at various life stages (Swarming Queen (SQ), 1-Year Queen (1YQ), 8-Year Queen (8YQ)) through transcriptomic, qRT-PCR, and enzyme activity analyses. Age-dependent upregulation of IIS pathway components (InR, chico, PDK1, Akt, Sirt1, FOXO) was observed, alongside the identification of six SOD transcripts, including two SOD1, two SOD2, and two SOD3 isoforms. Notably, mitochondrial SOD2 (particularly SOD2_b) showed a progressive increase with age, exhibiting the highest enzymatic activity and being associated with reduced mitochondrial oxidative stress and the disruption of reactive oxygen species (ROS) amplification cycles. These findings suggest that O. formosanus reproductives counteract the potential lifespan-reducing effects of chronic IIS activation by maintaining or enhancing FOXO activity, thereby supporting DNA repair, antioxidant defenses, and cellular homeostasis. The IIS-FOXO-SOD2 axis is identified as a key regulator of reproductive longevity in higher termites, offering new insights into the molecular mechanisms behind lifespan extension in social insects.