IMMUNITY, INFLAMMATION AND INFECTIONS DURING AGING
4. CONCLUSIONS
In conclusion, we can try to answer the question whether genes or genetic variants involved in immune response have an influence on the susceptibility to infections in the elderly. All the data here reported suggest that a “pro-inflammatory risk” with genetic bases exists. In addition, it is hypothesized that other genes (HLA genes, genes involved in stress response and energy metabolism) could also be relevant for susceptibility or resistance to infections, even if direct evidences are not yet available.
By the way, as discussed, these genes are mostly the same that have been claimed to be associated to human longevity (Franceschi et al., 2005). Indeed, it is conceivable that an allele variant of a gene having a protective effect against age-associated diseases can promote longevity. As stated at the beginning of this Chapter and discussed all along it, the immune function is of primary importance for survival, but likely our IS has been selected only to fit for survival at young ages, but not later on. Thus, one of the most important goal of the next years for biomedicine will be to increase the fitness of our IS with pharmacological or genetic strategies in order to allow it to work in optimal conditions even after 100 years of life.
NOTES
1. Cytokines: hormone-like proteins produced by many different cell types. They mediate inflammatory and immune reactions and affect the behaviour of other cells.
2. Phenotypical: related to all the physical characteristics (morphology, physiology, biochemical features) that result from genetic code.
3. Polymorphism: Natural variation in a gene, DNA sequence, that have no adverse effects on the individual and occurs with fairly high frequency in the general population. The most common polymorphisms are the so-called Single Nucleotide Polymorphisms” (SNPs), whose position on the sequence is indicated with “+” or “−” (e.g.−174;+874) basing on the fact that they are upstream or downstream of the transcription starting point.
4. Macrophages: resident large phagocytic cells derived from circulating monocytes.
5. Antigen-specific response: immune response specifically developed against different microbes and macromolecules.
6. Chemokines: family of structurally related glycoproteins with chemotactic and leukocyte activation activity.
7. Stressors: any chemical, physical, or biological entity that can induce adverse effects on cells or organisms.
8. Osteoporosis: a pathological condition in which there is a decrease in bone mass and bone density and an increased risk and/or incidence of bone fracture.
9. Sarcopenia: loss of muscle mass and function that, generally, comes with aging. This condition strongly influences muscle strength and mobility; it is a factor involved in the occurrence of frailty, falls and fractures in the elderly.
10. CD4+T helper cells: cells that carry the CD4 co-receptor protein and they are involved in the activation of monocytes and lymphocytes by secreting different types of cytokines.
11. CD8+T cytotoxic cells: cells that carry the co-receptor protein CD8 and they are involved in the killing of infected cells and tumour cells.
12. IgG: the most abundant immunoglobulin in the blood. It is responsible for the elimination of extracellular bacteria and toxins.
13. IgA: immunoglobulin that represents about 15 to 20% of immunoglobulins in the blood although it is primarily secreted across the mucosae. It is responsible for mucosal immunity.
IMMUNITY, INFLAMMATION AND INFECTIONS DURING AGING 25
14. IgM: it is the first antibody that is produced to the exposure to an antigen and it is important for the elimination of extracellular bacteria and toxins.
15. Autoantibodies: antibodies produced against the body’s own tissues. They are created by the immune system when it fails to recognize between “self” (the body’s normal constituents) and “non-self”
(foreign pathogens) and starts to attack its own cells, tissues, and/or organs, leading to the so-called
“auto immune diseases”.
16. Memory and effector antigen-experienced T cells: two T lymphocyte subpopulations in two different phases of their life, after antigen activation.
17. Clones: a population of cells derived from a single progenitor cell.
18. Thymic production: secreted by thymus, a primary lymphoid organ lying in the thoracic cavity, above and behind the heart.
19. Cytomegalovirus (CMV): member of the herpesvirus family, associated with persistent, latent and recurrent infection. It is usually not very harmful to healthy people.
20. Epstein Barr virus (EBV): human herpesvirus that usually causes an asymptomatic infection. It is the causative agent of infective mononucleosis and has been linked to the development of several cancers, particularly lymphomas in immunosuppressed persons.
21. Antigen processing: sequence of events that convert antigen protein into peptides which mount molecules of Major Hystocompatibility Complex (MHC, important molecules responsible for graft rejection).
22. Immunoproteasome: multimeric proteolitic complex inside the cytokine activated cells.
23. Longitudinal studies: research design where subjects are assessed at several different times in their lives in order to monitor the occurance of risk factors and the health status.
24. Mitogens: molecules able to induce cell division.
25. CD57+: cell-surface glycoprotein principally expressed on different types of cells such as NK, monocytes, some subsets of T and B cells.
26. CMV and EBV seropositivity: presence of antibodies to CMV and EBV in the blood detected by appropriate laboratory tests.
27. Enphysema: a lung pathology featuring the loss of lung elasticity and an abnormal accumulation of air in lung alveoli (tiny air sacs).
28. Chronic renal failure: a pathological condition featuring a slow and progressive deterioration of kidney function. It is also called kidney failure and is usually irreversible.
29. Pleiotropy: the phenomenon whereby a single gene affects several unrelated aspects of the phenotype of an organism.
30. Significant: a possible outcome of a significance test; it is performed to determine statistically if an observed value differs enough from a hypothesized value of a parameter. The choice of the
“statistically significant” value is somewhat arbitrary but by convention levels of .05 and .01 are most commonly used.
31. Promoter: short sequence of DNA to which specific enzymes bind in order to initiate transcription of a gene
32. Allele: one of several alternative forms of a gene or DNA sequence at a specific chromosomal locus. At each autosomal locus an individual possesses two alleles, one inherited from the father and one from the mother.
33. Cell repertoire: all the lymphocytes which recognize different antigens in the organism.
34. IL-7: cytokine involved in signalling between cells of the immune system with a specific role for lymphocyte maturation.
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