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Review
. 2020 Mar;15(2):83-93.
doi: 10.1097/COH.0000000000000609.

Senotherapeutics for HIV and aging

Matthew A Szaniawski  1 , Adam M Spivak
Affiliations
Review

Senotherapeutics for HIV and aging

Matthew A Szaniawski et al. Curr Opin HIV AIDS. 2020 Mar.

Abstract

Purpose of review: To summarize the state of chronic, treated HIV infection and its contribution to accelerated aging, and to evaluate recent research relevant to the study and treatment of aging and senescence.

Recent findings: Chronic treated HIV-1 infection is associated with significant risk of end-organ impairment, non-AIDS-associated malignancies, and accelerated physiologic aging. Coupled with the chronologic aging of the HIV-1-positive population, the development of therapies that target these processes is of great clinical importance. Age-related diseases are partly the result of cellular senescence. Both immune and nonimmune cell subsets are thought to mediate this senescent phenotype, a state of stable cell cycle arrest characterized by sustained release of pro-inflammatory mediators. Recent research in the field of aging has identified a number of 'senotherapeutics' to combat aging-related diseases, pharmacologic agents that act either by selectively promoting the death of senescent cells ('senolytics') or modifying senescent phenotype ('senomorphics').

Summary: Senescence is a hallmark of aging-related diseases that is characterized by stable cell cycle arrest and chronic inflammation. Chronic HIV-1 infection predisposes patients to aging-related illnesses and is similarly marked by a senescence-like phenotype. A better understanding of the role of HIV-1 in aging will inform the development of therapeutics aimed at eliminating senescent cells that drive accelerated physiologic aging.

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Conflict of interest statement

Conflicts of interest

none

Figures

Figure 1
Figure 1. Mechanisms and Clinical Consequences of HIV-1-Associated Inflammation
Untreated HIV-1 infection is characterized by profound immune activation (shown in red above), triggered by ongoing viral replication and exacerbated by microbial translocation and co-morbid conditions. Immune activation accelerates T cell loss, resulting in progression to AIDS. ART eliminates this feed-forward system, however low-level inflammation and immune exhaustion persist and result in a phenotype of immune senescence and increased risk of aging-related illnesses (shown in blue above).
See this image and copyright information in PMC

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