Tyrosine hydroxylase, insulin, and insulin growth are haplotypes located on chromosome 11p15. The aim of this study was to continue the exploration of the chromosomal region in human longevity by analyzing two additional markers, which are in the insulin and insulin growth factor genes. Both genes are good candidates for longevity, but neither marker revealed an association with longevity. Nevertheless, linkage disequilibrium and sex-specific longevity associations defined by both TH-INS and TH-IGF2 haplotypes reinforce the involvement of the chromosomal region spanning TH to IGF2 loci in controlling the longevity phenotype. The concerted action of stress-response pathways and energy-producing mechanisms is likely to be an evolutionarily successful strategy for long-term individual survival. Three genes, including tyrosine hydroxylase, insulin, and insulin growth factor, located on chromosome 11p15, are of considerable interest for human longevity.The DNA encodes proteins, including tyrosine hydroxylase which is the rate-limiting enzyme in the synthesis of catecholamines, amino acid-derived molecules produced by the sympathetic nervous system in response to stress. These act as both hormones (adrenaline) and neurotransmitters (dopamine and noradrenaline). INS encodes proinsulin, a single-chain precursor which is converted to insulin by enzymatic cleavage. A complex relationship exists between insulin and catecholamine regulation. IGF2 encodes insulin-like growth factor TI, also known as somatomedin, a single-chain polypeptide that shares an amino acid sequence homology with insulin. The INS-FokI-RFLP polymorphism lies inside the intron and acts as an enhancer transcription element in vitro. An association between this locus and human longevity was revealed. HUMTHOI alleles, Short (<22 repeats) and Long (≥22 repeats), showed a clear sex-dependent association with human longevity. Variability in INS and IGF2 was analyzed for genotypic and allelic counts and frequencies in 100-year-old subjects. The aim of this research was to continue exploring the chromosomal region related to human longevity by analyzing INS and IGF2 variability.