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Why are people with HIV considered "older adults" in their fifties? "immunosenescence"
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European Geriatric Medicine (April 2019)
Matilde Sanchez‑Conde1,2 · Jorge Díaz‑Alvarez1 · Fernando Dronda1 · Fatima Brañas3
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Accelerated Aging in HIV+ / immunosenescence are directly related to the premature onset of other end-organ diseases.
the identification of patients who are at risk for unhealthy aging has become relevant for the care of older adults with HIV......nvestigators used the epigenetic clock to measure age acceleration even though the HIV infection was under control. Gross et al.....These authors found that both chronic and recent HIV infections lead to an average aging advancement of 4.9 years and a 19% increase in expected mortality risk......iNelson et al. [22] assessed the difference in DNA methylation among antiretroviral treatment in (ART)-naïve, HIV-positive and HIV-negative individuals and found that the DNA methylation age was 11.2 years higher in HIV-positive individuals than in HIV-negative ones. Moreover, Horvath and colleagues [8] have shown that HIV infection leads to an increase in the epigenetic age of brain tissue (7.4 years) and blood (5.2 years). A recent study published by Levine et al......The early onset of comorbidities and functional impairment among PLWH is based in the evidence that, despite optimal suppression of HIV replication after starting ARV, there is persistent and chronic activation of the immune system leading to the release of inflammation mediators. This immune activation arises from the persistent gut microbial translocation, sustained chronic antigenic stimulation, low-level HIV viremia, and coinfections by persistent pathogens. Constant stimulation of the immune system activates some of the changes to the adaptive immunity that are seen in the very old and leads to immune exhaustion and accelerated immunosenescence. HIV-associated inflammation and immunosenescence are directly related to the premature onset of other end-organ diseases.
Abstract
One in six new HIV diagnoses in Europe occur among people over 50 years of age. As in the general population, the aging process is not homogeneous among older adults with HIV, and some of them exhibit impaired physical function, higher frailty and more frequent geriatric syndromes. These illness reflect a higher biological age independently of their chronological age. After starting antirretroviral treatment, people living with HIV (PLWH) older than 50 exhibit a poorer immunological recovery than younger PLWH. Moreover, older adults with HIV present early onset of comorbidities and functional impairment caused by persistent and chronic activation of the immune system, which leads to immune exhaustion and accelerated immunosenescence despite optimal suppression of HIV replication. The evidence of poorer immunological response to ARV, linked with early immunosenescence in PLWH and its prematurely deleterious effect in physiological functions and its clinical consequences, are the basis to accept the cut-off of 50 years of age to define an "older adult with HIV".
The early onset of comorbidities and functional impairment among PLWH is based in the evidence that, despite optimal suppression of HIV replication after starting ARV, there is persistent and chronic activation of the immune system leading to the release of inflammation mediators. This immune activation arises from the persistent gut microbial translocation, sustained chronic antigenic stimulation, low-level HIV viremia, and coinfections by persistent pathogens. Constant stimulation of the immune system activates some of the changes to the adaptive immunity that are seen in the very old and leads to immune exhaustion and accelerated immunosenescence. HIV-associated inflammation and immunosenescence are directly related to the premature onset of other end-organ diseases [44, 45, 46, 47].
The evidence of poorer immunological response to ARV, linked with early immunosenescence in PLWH and its prematurely deleterious effect in physiological functions and its clinical consequences, are the basis to currently accept the cut-off of 50 years of age to define an "older adult with HIV".
Similar to the general population, aging is not homogeneous among PLWH. In addition, previously published data reveals an increased biological age in HIV-infected versus non-HIV-infected individuals, even if viral replication is suppressed [8]. Moreover, PLWH is a population group with an increased prominence of age-related comorbid illnesses with respect to the non-HIV population [9]. Furthermore, these comorbidities appear early and include higher rates of functional impairment and geriatric syndromes such as frailty, which may become up to twice as prevalent in comparison to non-infected individuals who are 10 years older [10, 11, 12].
Thus, the identification of patients who are at risk for unhealthy aging has become relevant for the care of older adults with HIV.
Regarding the HIV population, some investigators used the epigenetic clock to measure age acceleration even though the HIV infection was under control. Gross et al. [21] investigated the impact of chronic HIV infection on aging by performing a global analysis of the whole-blood DNA methylomes of 137 HIV-positive individuals under a stable antiretroviral treatment and comparing them with those of 44 matched HIV-negative individuals. These authors found that both chronic and recent HIV infections lead to an average aging advancement of 4.9 years and a 19% increase in expected mortality risk. In another study with participants from the Veterans Aging Cohort Study, Nelson et al. [22] assessed the difference in DNA methylation among antiretroviral treatment in (ART)-naïve, HIV-positive and HIV-negative individuals and found that the DNA methylation age was 11.2 years higher in HIV-positive individuals than in HIV-negative ones. Moreover, Horvath and colleagues [8] have shown that HIV infection leads to an increase in the epigenetic age of brain tissue (7.4 years) and blood (5.2 years). A recent study published by Levine et al. [23] already determined an association between an HIV infection with neurocognitive disorders (HAND) and higher biological age. The most important studies that use DNA methylation to assess a higher biological age is associated with HIV infection are shown in Table 1
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