Senotherapeutics for HIV and aging

Curr Opin HIV AIDS. 2020 Mar;15(2):83-93. doi: 10.1097/COH.0000000000000609.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / pathology*
  • Aniline Compounds / pharmacology
  • Antibiotics, Antineoplastic / pharmacology
  • Antineoplastic Agents / pharmacology
  • Antiretroviral Therapy, Highly Active / adverse effects*
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • CD4-CD8 Ratio
  • Cardiovascular Diseases
  • Cell Cycle Checkpoints
  • Cellular Senescence / drug effects*
  • HIV Infections* / drug therapy
  • HIV Infections* / pathology
  • HIV-1
  • Histone Deacetylase Inhibitors / pharmacology
  • Humans
  • Inflammation / immunology
  • Janus Kinases / pharmacology
  • Nitriles
  • Panobinostat / pharmacology
  • Pyrazoles / pharmacology
  • Pyrimidines
  • Sirolimus / pharmacology
  • Sulfonamides / pharmacology
  • T-Lymphocyte Subsets / immunology

Substances

  • Aniline Compounds
  • Antibiotics, Antineoplastic
  • Antineoplastic Agents
  • Bridged Bicyclo Compounds, Heterocyclic
  • Histone Deacetylase Inhibitors
  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • Sulfonamides
  • ruxolitinib
  • Panobinostat
  • Janus Kinases
  • venetoclax
  • Sirolimus
  • navitoclax