title: Age-Associated ALU Element Instability in White Blood Cells Is Linked to Lower Survival in Elderly Adults: A Preliminary Cohort Study.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Internal Medicine, Division of Geriatrics, University of Utah School of Medicine, University of Utah, Salt Lake City, Utah, United States of America.|Geriatric Research, Education, and Clinical Center, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, United States of America.
authors.forename: R Garrett
authors.identifier: http://orcid.org/0000-0003-2574-3508
authors.initials: RG
authors.lastname: Morgan
authors.affiliation: Department of Internal Medicine, Division of Geriatrics, University of Utah School of Medicine, University of Utah, Salt Lake City, Utah, United States of America.|Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.|Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Venturelli
authors.affiliation: Department of Internal Medicine, Division of Geriatrics, University of Utah School of Medicine, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Cole
authors.initials: C
authors.lastname: Gross
authors.affiliation: Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Cantor
authors.initials: C
authors.lastname: Tarperi
authors.affiliation: Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Schena
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padova, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Reggiani
authors.affiliation: DAHFMO-Unit of Histology and Medical Embryology, Sapienza University, Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Naro
authors.affiliation: Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Pedrinolla
authors.affiliation: Department of Physiology and Pharmacology, Sapienza University of Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Monaco
authors.affiliation: Department of Internal Medicine, Division of Geriatrics, University of Utah School of Medicine, University of Utah, Salt Lake City, Utah, United States of America.|Geriatric Research, Education, and Clinical Center, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, United States of America.|Department of Health, Kinesiology, and Recreation, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
authors.affiliation: Department of Internal Medicine, Division of Geriatrics, University of Utah School of Medicine, University of Utah, Salt Lake City, Utah, United States of America.|Geriatric Research, Education, and Clinical Center, George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, Utah, United States of America.|Department of Health, Kinesiology, and Recreation, University of Utah, Salt Lake City, Utah, United States of America.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Donato
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D020087:Alu Elements; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics / Q000401:mortality; D005260:Female; D042822:Genomic Instability; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D009369:Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000401:mortality; D015996:Survival Rate; D059505:Telomere Homeostasis; D055815:Young Adult
chemical_list: D015415:Biomarkers