Aging is an exceptionally complex process that depends on genetic, environmental, and lifestyle factors. Previous studies within the International HLA and Immunogenetics Workshop (IHIWS) component “Immunogenetics of Ageing” showed that longevity is associated with positive selection of HLA-DRB1*11- and DRB1*16-associated haplotypes, shown to be protective against diseases. Within the 18th IHIWS, we aimed to investigate the relevance of telomere length for successful aging and its association with classical HLAs. In total 957 individuals from Bulgaria, Turkey, Romania, and Poland in two age groups, elderly individuals (age 65–99 years) and ethnically matched young group (age 18–64 years), were investigated. The obtained results confirmed interpopulation differences in the distribution of HLA alleles, documented the lengths of telomeres in analyzed populations, and demonstrated significant associations of telomere length with aging as well as with the presence of some HLA class I or class II alleles. They suggest that telomere length assessment combined with HLA genotyping may help identify immunogenetic profiles associated with longevity. The associations between HLA and telomeres support the theory that HLA genes influence the aging process. However, further research is needed to clarify the biological basis of the observed relationships.

The human life span could be influenced by the combined effect of environment, lifestyle, and genetic factors. Twin and family studies suggest that our genes control up to 25% of the lifespan. The aging immune system undergoes age-associated changes at multiple levels, resulting in a gradual loss of its ability to protect the organism against infections, low vaccine responses, and an increased probability of developing autoimmune diseases and malignancies. The highly polymorphic HLA complex is one of the major gene candidates associated with aging due to its crucial role in developing adaptive immunity and protecting the organism. Most of the data available have so far demonstrated a positive association with healthy aging for HLA alleles/haplotypes as protective against malignancies, autoimmune diseases, and conferring better control and response to infections. One of aging’s main manifestations is the chronic, low-grade inflammatory state observed in older people, caused by an imbalance between pro- and anti-inflammatory cytokines. In general, it is has been agreed that longevity is related to anti-inflammatory genotype profiles. With advanced age, changes also occur in the B cell repertoire, which significantly affects the humoral immunity and leads to inadequate responses to infections and vaccines in the elderly. New genetic biomarkers associated with aging are being explored and discovered, contributing to a better understanding of the molecular processes underlying the immune dysfunction related to aging and developing strategies for rejuvenating the immune system based on immune-risk phenotypes.