In contrast to shorter-term restriction, long-term caloric restriction (60% kcals of normal chow) for 28 weeks (~12 human years) in aged mice (52W) was found to reduce senescent VAT and splenic PD-1+ CD4+ and PD-1+ CD8+ T cells; improve glucose tolerance, insulin resistance, fasting serum insulin, and leptin levels; lower weight; and increase serum adiponectin levels, as compared to normal chow-fed aged mice. This evidence concerns the gene INS and Insulin resistance.