title: Premature aging and immune senescence in HIV-infected children.
abstract: Several pieces of evidence indicate that HIV-infected adults undergo premature aging. The effect of HIV and antiretroviral therapy (ART) exposure on the aging process of HIV-infected children may be more deleterious since their immune system coevolves from birth with HIV.
  
  
  
  Seventy-one HIV-infected (HIV+), 65 HIV-exposed-uninfected (HEU), and 56 HIV-unexposed-uninfected (HUU) children, all aged 0-5 years, were studied for biological aging and immune senescence.
  
  
  
  Telomere length and T-cell receptor rearrangement excision circle levels were quantified in peripheral blood cells by real-time PCR. CD4 and CD8 cells were analysed for differentiation, senescence, and activation/exhaustion markers by flow cytometry.
  
  
  
  Telomere lengths were significantly shorter in HIV+ than in HEU and HUU children (overall, P < 0.001 adjusted for age); HIV+ ART-naive (42%) children had shorter telomere length compared with children on ART (P = 0.003 adjusted for age). T-cell receptor rearrangement excision circle levels and CD8 recent thymic emigrant cells (CD45RACD31) were significantly lower in the HIV+ than in control groups (overall, P = 0.025 and P = 0.005, respectively). Percentages of senescent (CD28CD57), activated (CD38HLA-DR), and exhausted (PD1) CD8 cells were significantly higher in HIV+ than in HEU and HUU children (P = 0.004, P < 0.001, and P < 0.001, respectively). Within the CD4 cell subset, the percentage of senescent cells did not differ between HIV+ and controls, but programmed cell death receptor-1 expression was upregulated in the former.
  
  
  
  HIV-infected children exhibit premature biological aging with accelerated immune senescence, which particularly affects the CD8 cell subset. HIV infection per se seems to influence the aging process, rather than exposure to ART for prophylaxis or treatment.
authors.affiliation: aDepartment of Surgery, Oncology and Gastroenterology - DiSCOG, Section of Oncology and Immunology, Unit of Viral Oncology and AIDS Reference Center, University of Padova, Padova, Italy bUnitat d'Infectologia, Servei de Pediatria; Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain cIstituto Oncologico Veneto (IOV) - IRCCS dDepartment of Mother and Child Health, University of Padova, Padova, Italy eClinical Laboratory Department, Hematology Unit, Hospital San Joan de Déu, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Ketty
authors.initials: K
authors.lastname: Gianesin
authors.forename: Antoni
authors.initials: A
authors.lastname: Noguera-Julian
authors.forename: Marisa
authors.initials: M
authors.lastname: Zanchetta
authors.forename: Paola
authors.initials: P
authors.lastname: Del Bianco
authors.forename: Maria Raffaella
authors.initials: MR
authors.lastname: Petrara
authors.forename: Riccardo
authors.initials: R
authors.lastname: Freguja
authors.forename: Osvalda
authors.initials: O
authors.lastname: Rampon
authors.forename: Clàudia
authors.initials: C
authors.lastname: Fortuny
authors.forename: Mireia
authors.initials: M
authors.lastname: Camós
authors.forename: Elena
authors.initials: E
authors.lastname: Mozzo
authors.forename: Carlo
authors.initials: C
authors.lastname: Giaquinto
authors.forename: Anita
authors.initials: A
authors.lastname: De Rossi
mesh_terms: D019588:Aging, Premature; D015415:Biomarkers / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000502:physiology; D002454:Cell Differentiation; D016922:Cellular Senescence; D002675:Child, Preschool; D005260:Female; D015321:Gene Rearrangement; D015658:HIV Infections / Q000473:pathology*; D006801:Humans; D055633:Immune System Phenomena; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008297:Male; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D059506:Telomere Shortening
chemical_list: D015415:Biomarkers; D011948:Receptors, Antigen, T-Cell