There are differences in the allele frequency of MTHFR polymorphism between Western and African population. The aim of this study is to determinate the prevalence of MTHFR C677T and A1298C polymorphisms in young and old people living in different areas from Mediterranean to sub-Saharan areas. The observed vs expected genotype frequencies of 677T were in Hardy Weinberg equilibrium, with the exception of old Sardinian subjects (P=0.02). Calculation of 677T allele frequency in young and old African subjects (8% and 3%, respectively) indicated that the 677T allele was disadvantaged in old Africans (P=0.02). The difference among young and old Sardinians and Sicilians were not significant at the same degree (43% vs 37% P=0.07 and 46% vs 42% P=0.28,respectively). However, the reproducible trend that showed the prevalence of 677T allele in the young subjects of the three studied areas confirms the disadvantage of this polymorphism with the age. There was a significant difference (P=0.005) on the observed vs expected frequency of 1298C homozygosity in African old subjects compared to younger ones, while the observed vs expected genotypefrequencies were in equilibrium in young and old Sardinian and Sicilian subjects. The frequencies of 1298C and 1298A alleles were comparable between young and old African, Sardinian and Siciliansubjects. The lower frequency of 677T allele in old African, Sardinian and Sicilian subjects compared to young ones and the absence of TT genotype among old African subjects, should be considered as a consequence of an elevated mortality of 677T carriers.