But the high FGF21 and GDF15 levels observed in older people (Conte et al., 2019), and elevated GDF15 in type 2 diabetes patients (Conte et al., 2021) and in some cancers might also indicate that these mitokines promote aging or even disease and that thus keeping nuclear mitokine levels low may be best, maybe by increasing efficient mitokine signaling (via abolishing resistance and tolerance effects). The gene discussed is FGF21; the disease is type 2 diabetes mellitus.