Conversely, plasma GDF15 levels are higher in the elderly, in particular in the presence of pathological conditions, such as CVD, insulin resistance and T2D, neurodegeneration, renal chronic disease and cancer [50, 55], where it is supposed that GDF15 plays a protective role against different insults via PI3K–Akt, ERK1/2 and SMAD2/3 signalling pathways [68–71]. The gene discussed is GDF15; the disease is Insulin resistance.