Project in the Spotlight
This time, we highlight the project Immunogenetics of Ageing organised by Elissaveta Naumova, Milena Ivanova, Graham Pawelec.
Deterioration of the immune system with aging is associated with an increased susceptibility to infectious diseases, cancer and autoimmune disorders. Many studies have focused on age-associated changes in immune functions which might contribute to these pathologies. It has been demonstrated that aging is associated with chronic, low-grade inflammatory activity. The aging process is very complex and longevity is a multifactorial trait, which is determined by genetic and environmental factors, and the interaction of “disease” processes with “intrinsic” ageing processes. It is hypothesized that the level of immune response as well as possibly longevity could be associated with genes regulating immune functions. It is further hypothesized that the diversity of these genes might influence successful aging and longevity by modulating an individual´s response to life-threatening disorders. Several studies have focused on the role of immune gene polymorphisms for human longevity. However, available data do not allow at present to clarify the role of these genes due to major methodological problems, such as the typing approach and focusing on single loci, insufficient sample size, different inclusion criteria and age limits, inappropriate control matching and neglected considerations of sex-related effects and the different genetic make-up of studied populations.
The aim of the component “Immunogenetics of Ageing” is to identify new biomarkers for successful aging and an increased capacity to reach the extreme limits of life-span by analysis of immune response genes. Within 18th IHIW we plan to confirm and clarify the functional relevance of the possible biomarkers, defined in previous workshops, in a larger cohort of healthy elderly, elderly patients with age-associated diseases and controls (young and middle age) from different populations
The study will include unrelated elderly individuals (octogenarians and nonagenarians) and families with longevity members. The following selection criteria will be used to identify families for the study:
- extended families with a family history of at least two generations with longevity members (octogenarians and nonagenarians) including: elderly individuals, their children and grandchildren
- sufficient demographic data should be available
- data on family history of diseases should be available
Elderly individuals (in family-based analyses and unrelated case-control analyses) selected should ideally be characterized according to the SENIEUR or nearly – SENIEUR protocols.
Ethnically matched unrelated young controls should ideally be characterized according to JUNIER protocol. Ethnically matched middle aged controls will also be included in the study.
Comparisons with young and middle – aged controls will be performed. The project will be focused on the following candidate biomarkers: classical HLA loci (HLA-A,-B,-C,-DRB1/3/4/5, -DQB1,-DQA1, -DPA1, -DPB1), genes in the extended MHC region such as MICA and MICB, polymorphisms in pro- and anti-inflammatory cytokine genes (IL-2, IL-6, IL-10, IL-12, IFNγ, TNFα, TGFβ) with possible correlation to the level of gene expression, KIR, BCR and TCR. Linkage and Association analyses and correlation with functional parameters, defining immune risk profiles will be performed. Additionally relevant markers will be analyzed in well characterized cell clones from elderly and controls, collected and established during the previous projects focusing on immunosenescence and aging.
To declare your interest to join this Component, please fill the form on the 18th IHIW website at https://www.ihiw18.org/component-ngs-for-hla/aging/.