HIV and aging, biological mechanisms, and therapies: What do we know?
Tomás M. Grosso 1, José Alcamí 2, José R. Arribas 3, Marta Martín 4, Irini Sereti 5, Philip Tarr 6, Pedro Cahn 7, Bonaventura Clotet 8, Omar Sued 7, Eugenia Negredo 9
1 Department of Clinical Research, Fundación Huésped, Buenos Aires, Argentina; Laboratory of Immunology, Universidad Nacional de Luján, Luján, Argentina; 2 AIDS Immunopathogenesis Unit, Instituto de Salud Carlos III, Madrid; HIV Unit, Hospital Clínic de Barcelona, IDIBAPS, Barcelona; CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid. Spain; 3 HIV Unit, La Paz Hospital, IdiPAZ, Madrid, Spain; 4 Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona. Spain; 5 Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA; 6 Department of Medicine and Infectious Diseases Service, Kantonsspital Baselland, University of Basel, Basel, Switzerland; 7 Department of Clinical Research, Fundación Huésped, Buenos Aires, Argentina; 8 AIDS Research Institute-IRSICAIXA, Hospital Universitari Germans Trias i Pujol Badalona, Universitat Autònoma de Barcelona, Barcelona; Universitat de Vic - Universitat Central de Catalunya, Vic. Spain; 9 Universitat de Vic - Universitat Central de Catalunya, Vic; Lluita contra la Sida Foundation, Hospital Universitari Germans Trias i Pujol, Badalona, Universitat Autònoma de Barcelona, Barcelona. Spain
*Correspondence: Bonaventura Clotet, Email not available
Abstract
Aging, a time-dependent loss of physiological function, and its drivers are turning into a significant topic of research as the population's mean age increases. Epigenetic alterations, telomere shortening or dysfunction, mitogenic stress, oxidative stress, or accumulation of DNA damage can drive the cell to senescence: a permanent cell cycle arrest sometimes associated with a secretory phenotype and inflammatory consequences in the surrounding tissue. The amount of senescent cells grows over time in older organisms and may induce tissue inflammation and threaten overall tissue homeostasis, favoring aging. Senolytic and senomorphic therapeutics are an emerging approach to eliminate senescent cells or to block their secretory phenotypes respectively. Given that people living with HIV suffer non-AIDS comorbidities in a higher prevalence than the general population, aging is accentuated among them. Inflammation biomarkers may be helpful to assess prognosis or act as surrogate endpoints for studies of strategies focused on reversal of HIV-associated accelerated aging. This review summarizes the latest findings in aging and its major drivers, under the light of HIV infection. Since the number of older PLWH is currently rising, it will be of great importance to address and treat their age-related conditions, as well as to better decipher their biological mechanisms.
