BACKGROUND: ALU element instability could contribute to gene function variance in aging, and may partly explain variation in human lifespan. OBJECTIVE: To assess the role of ALU element instability in human aging and the potential efficacy of ALU element content as a marker of biological aging and survival. DESIGN: Preliminary cohort study. METHODS: We measured two high frequency ALU element subfamilies, ALU-J and ALU-Sx, by a single qPCR assay and compared ALU-J/Sx content in white blood cell (WBCs) and skeletal muscle cell (SMCs) biopsies from twenty-three elderly adults with sixteen healthy sex-balanced young adults; all-cause survival rates of elderly adults predicted by ALU-J/Sx content in both tissues; and cardiovascular disease (CVD)- and cancer-specific survival rates of elderly adults predicted by ALU-J/Sx content in both tissues, as planned subgroup analyses. RESULTS: We found greater ALU-J/Sx content variance in WBCs from elderly adults than young adults (P < 0.001) with no difference in SMCs (P = 0.94). Elderly adults with low WBC ALU-J/Sx content had worse four-year all-cause and CVD-associated survival than those with high ALU-J/Sx content (both P = 0.03 and hazard ratios (HR) ≥ 3.40), while WBC ALU-J/Sx content had no influence on cancer-associated survival (P = 0.42 and HR = 0.74). SMC ALU-J/Sx content had no influence on all-cause, CVD- or cancer -associated survival (all P ≥ 0.26; HR ≤ 2.07). CONCLUSIONS: These initial findings demonstrate that ALU element instability occurs with advanced age in WBCs, but not SMCs, and imparts greater risk of all-cause mortality that is likely driven by an increased risk for CVD and not cancer.

Age-associated ALU element instability in white blood cells is linked to lower survival in elderly adults: a preliminary cohort study

VENTURELLI, Massimo;TARPERI, Cantor;SCHENA, Federico;PEDRINOLLA, ANNA;
2017

Abstract

BACKGROUND: ALU element instability could contribute to gene function variance in aging, and may partly explain variation in human lifespan. OBJECTIVE: To assess the role of ALU element instability in human aging and the potential efficacy of ALU element content as a marker of biological aging and survival. DESIGN: Preliminary cohort study. METHODS: We measured two high frequency ALU element subfamilies, ALU-J and ALU-Sx, by a single qPCR assay and compared ALU-J/Sx content in white blood cell (WBCs) and skeletal muscle cell (SMCs) biopsies from twenty-three elderly adults with sixteen healthy sex-balanced young adults; all-cause survival rates of elderly adults predicted by ALU-J/Sx content in both tissues; and cardiovascular disease (CVD)- and cancer-specific survival rates of elderly adults predicted by ALU-J/Sx content in both tissues, as planned subgroup analyses. RESULTS: We found greater ALU-J/Sx content variance in WBCs from elderly adults than young adults (P < 0.001) with no difference in SMCs (P = 0.94). Elderly adults with low WBC ALU-J/Sx content had worse four-year all-cause and CVD-associated survival than those with high ALU-J/Sx content (both P = 0.03 and hazard ratios (HR) ≥ 3.40), while WBC ALU-J/Sx content had no influence on cancer-associated survival (P = 0.42 and HR = 0.74). SMC ALU-J/Sx content had no influence on all-cause, CVD- or cancer -associated survival (all P ≥ 0.26; HR ≤ 2.07). CONCLUSIONS: These initial findings demonstrate that ALU element instability occurs with advanced age in WBCs, but not SMCs, and imparts greater risk of all-cause mortality that is likely driven by an increased risk for CVD and not cancer.
ALU element; instability; aging; human; cohort study; white blood cell; skeletal muscle cell; ALU-J/Sx content; cardiovascular disease; cancer; human lifespan
File in questo prodotto:
File Dimensione Formato  
journal.pone.0169628.pdf

accesso aperto

Descrizione: CC BY 4.0 publisher's version
Tipologia: Versione dell'editore
Licenza: Creative commons
Dimensione 1.73 MB
Formato Adobe PDF
1.73 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/955985
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 4
social impact