Decrypting biological hallmarks of aging in people with HIV

Abstract

Purpose of review HIV infection adds further complexity to the heterogenous process of aging. In this focused review, we examine and discuss recent advances to better elucidate mechanisms of biological aging perturbed and accelerated in the context of HIV, particularly among those with viral suppression through the benefits of antiretroviral therapy (ART). New hypotheses from these studies are poised to provide an improved understanding of multifaceted pathways that converge and likely form the basis for effective interventions toward successful aging. Recent findings Evidence to date suggests multiple mechanisms of biological aging impact people living with HIV (PLWH). Recent literature delves and expands on how epigenetic alterations, telomere attrition, mitochondrial perturbations, and intercellular communications may underpin accelerated or accentuated aging phenotypes and the disproportionate prevalence of age-related complications among PLWH. Although most hallmarks of aging are likely exacerbated in the setting of HIV, ongoing research efforts are providing new insight on the collective impact these conserved pathways may have in the aging disease processes. Summary New knowledge on underlying molecular disease mechanisms impacting people aging with HIV are reviewed. Also examined are studies that may facilitate the development and implementation of effective therapeutics and guidance on improving geriatric HIV clinical care.

Accelerated Neuroimmune Dysfunction in Aged HIV-1-Infected Humanized Mice

“…PLWH often exhibit complications of premature aging such as cardiovascular [ 28 ], cancer [ 29 ], renal [ 30 ], metabolic [ 31 ], and neurocognitive disorders [ 32 , 33 ], even when virus infection is ART-suppressed. The mechanistic reasons could be due to a combination of factors that include persistent immune activation and inflammation, genomic and epigenetic alterations, cell aging, mitochondrial energy [ 34 , 35 , 36 ], and metabolic shifts [ 31 , 37 ], with or without ART [ 38 ]. Several mechanisms are linked to PLWH premature aging [ 27 , 39 , 40 , 41 , 42 ].…”

“…This includes neutrophil extracellular trap signaling, DC maturation, and NK cell signaling, which are all responsible for the viral clearance and activation of adaptive immunity during HIV infection [ 60 , 62 , 63 ]. The other affected pathway of importance is diminished activity of mitochondrial function, which could be associated with potential cellular energy deficits in PLWH [ 38 ]. We also observed aging-related alternations such as cellular senescence, a loss of proteostasis, and epigenetic alterations in our infected and aged hu-mice, suggesting that chronic CNS viral infection may be contributing to premature aging through various mechanisms beyond immune activation and neuroinflammation.…”