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 / Morgan, R. Garrett; Venturelli, Massimo; Gross, Cole; Tarperi, Cantor; Schena, Federico; Reggiani, Carlo; Naro, Fabio; Pedrinolla, Anna; Monaco, Lucia; Richardson, Russell S; Donato, Anthony J.. - In: PLOS ONE. - ISSN 1932-6203. - ELETTRONICO. - 12:1(2017), pp. 1-14. [10.1371/journal.pone.0169628]

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

NARO, Fabio;MONACO, Lucia;
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
2017
ALU; cells; blood; adults
01 Pubblicazione su rivista::01a Articolo in rivista
Age-associated ALU element instability in white blood cells Is linked to lower survival in elderly adults: a preliminary cohort study / Morgan, R. Garrett; Venturelli, Massimo; Gross, Cole; Tarperi, Cantor; Schena, Federico; Reggiani, Carlo; Naro, Fabio; Pedrinolla, Anna; Monaco, Lucia; Richardson, Russell S; Donato, Anthony J.. - In: PLOS ONE. - ISSN 1932-6203. - ELETTRONICO. - 12:1(2017), pp. 1-14. [10.1371/journal.pone.0169628]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/936596
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