"Inflammaging" refers to activation of the innate and adaptive immunity, which leads to immunosenescence and is associated with the incidence of age-associated disease. Long-term treated HIV-infected individuals show chronic inflammation, and persistent bacterial translocation secondary to an altered gut mucosa and reactivation of latent viruses are likely major drivers. In the general population, chronic inflammation predicts a number of pathologies associated with aging. Is there any parallel between the determinants of chronic inflammation in treated HIV-infected individuals and the HIV-uninfected? Is treated HIV infection a clinical model of premature aging?
They do. There are several common features between the immune system of HIV-1 chronically infected patients and the one of healthy elderly individuals such as for example dysregulated expression of AID (activation-induced deaminase) which is the enzyme triggering immunoglobulin affinity maturation on B-cells during an immune response and increased CD27-IgD- (double negative) B-cells. Both have been shown to be inversely related to the magnitude of immune response upon flu vaccination. Here are a few references for HIV-1 infected patients: Cagigi A et al. Vaccine. 2013 Apr 26;31(18):2231-7; Cagigi A et al. J Allergy Clin Immunol. 2013 Nov 28. pii: S0091-6749(13)01550-9 and for aged individuals: Frasca D et al. Int Immunol. 2012 Mar;24(3):175-82; Colonna-Romano G et al. Mech Ageing Dev. 2009 Oct;130(10):681-90.
You might find Steve Deek's work and opinions useful.-
- High KP, et al. HIV and Aging Working Group. , J Acquir Immune Defic Syndr. 2012 Jul 1;60 Suppl 1:S1-18. doi: 10.1097/QAI.0b013e31825a3668.
- Deeks SG, Verdin E, McCune JM. Curr Opin Immunol. 2012 Aug;24(4):501-6. doi: 10.1016/j.coi.2012.05.004. Epub 2012 Jun 2. Review.
Yes if aging equates gradual damage from low level
inflammatIon; please check Miedema et al Frontiers Immunol for a thorough
Review of effects and mechanisms of
Inflammation in hiv infection, treated and untreated
HIV-1 infection is indeed only one example. Similar levels of double negative B-cells are also found in kidney transplant patients who, like HIV-1 infected patients, may be subjected to chronic immune activation due to the presence of a foreign organ and are immune suppressed due to the therapies following transplantation: Cagigi A et al. Clin Exp Immunol. 2013 Nov;174(2):274-80.
Age is associated with increased immune function backlog, and this effect is also a primary effect of HIV infection. Constant attempts by the body to equalize lead to inflammation without resulting in completion of this backlog, hence chronic inflammation. HIV definitely causes premature aging, both by physical appearance and by the onset of age related disorders such as cancer, Alzeimers and hypertension.
Great comments. But think about chronically treated HIV infected individuals, presumably on long-term viral suppression, i.e., undetectable HIV RNA in blood. They still show higher levels of inflammatory markers compared to HIV-uninfected controls. In this setting, the factors driving inflammation are widely assumed to be increased bacterial translocation, replication of herpes-virus and possibly residual viremia in cellular reservoirs and anatomical sanctuaries. HIV is a clinical model of premature aging. Any thought about the triggers of chronic inflammation in the general population?
Sergio, it is known that HIV progresses in the body, particularly in the brain even with long term viral suppression to undetectable levels. This, I assume, is due to monocyte trafficking from the bone marrow niche to the brain. The presence of continuous active infection in the bone marrow means the immune response is kept on its toes and inflammatory reaction is mostly due to this. Bacterial and viral factors probably contribute to the inflammation, but the increased translocation is probably due to reduced immune function despite viral control. Importantly, attempts by the immune system to vanquish secondary viral reservoirs will invariably lead to acute inflammation such as that observed during IRIS
In both cases (HIV-1+ and healthy elderly individuals), a big part of the chronic imune activation is caused by increased microbial translocation/pathogen reactivation. The difference between the two is that while during HIV-1 infection this is great in the beginning (due to lymphopenia) and leads to cumulative lymphocyte exhaustion (premature aging), during healthy aging, lymphocyte exhaustion naturally happens gradually morrowing increasing pathogen activity.
Increased microbial translocation/pathogen reactivation is NOT caused by lymphocyte loss in both cases but general immune response reduction and finally failure of the immune system as a whole. This I know for a fact because I have patients who have maintained a CD4 count of 7 and less for more than a year without any health problems in my cure experiments. However, immune reconstitution such as that achieved during the cure has also caused severe increased microbial translocation/pathogen reactivation, sometimes to life threatening proportions. General immune function integrity failure can cause increased microbial translocation/pathogen reactivation even when lymphocyte levels are sufficient.
This is what I wrote previously, let me highlight and explain something: "...The difference between the two is that while during HIV-1 infection this is great IN THE BEGINNING (due to lymphopenia) and leads to CUMULATIVE lymphocyte exhaustion (even after immune reconstitution several B and T cell defects remain), during healthy aging, LYMPHOCYTE EXHAUSTION NATURALLY HAPPENS gradually morrowing increasing pathogen activity (this means loss of fuction leads to pathogen reactivation in the elderly).
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