Accelerated Cell Aging in Female APOE-ε4 Carriers: Implications for Hormone Therapy Use
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{"title"=>"Accelerated Cell Aging in Female APOE-ε4 Carriers: Implications for Hormone Therapy Use", "type"=>"journal", "authors"=>[{"first_name"=>"Emily G.", "last_name"=>"Jacobs", "scopus_author_id"=>"55597831100"}, {"first_name"=>"Candyce", "last_name"=>"Kroenke", "scopus_author_id"=>"6601935569"}, {"first_name"=>"Jue", "last_name"=>"Lin", "scopus_author_id"=>"7501725008"}, {"first_name"=>"Elissa S.", "last_name"=>"Epel", "scopus_author_id"=>"35416705700"}, {"first_name"=>"Heather A.", "last_name"=>"Kenna", "scopus_author_id"=>"9738136900"}, {"first_name"=>"Elizabeth H.", "last_name"=>"Blackburn", "scopus_author_id"=>"7103349740"}, {"first_name"=>"Natalie L.", "last_name"=>"Rasgon", "scopus_author_id"=>"7003319011"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84873911119", "sgr"=>"84873911119", "pui"=>"368342490", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"23418430", "doi"=>"10.1371/journal.pone.0054713"}, "id"=>"07316c28-77fa-304d-93ec-534943af1925", "abstract"=>"Apolipoprotein-ε4 (APOE-ε4) is a major genetic risk factor for cognitive decline, Alzheimer's disease (AD) and early mortality. An accelerated rate of biological aging could contribute to this increased risk. Here, we determined whether APOE-ε4 status impacts leukocyte telomere length (TL) and the rate of cellular senescence in healthy mid-life women and, further, whether hormone replacement therapy (HT) modifies this association. Post-menopausal women (N = 63, Mean age = 57.7), all HT users for at least one year, were enrolled in a randomized longitudinal study. Half of the participants (N = 32) remained on their HT regimen and half (N = 31) went off HT for approximately two years (Mean  = 1.93 years). Participants included 24 APOE-ε4 carriers and 39 non-carrier controls. Leukocyte TL was measured at baseline and the end of year 2 using quantitative polymerase chain reaction. Logistic regression analysis indicated that the odds of an APOE-ε4 carrier exhibiting telomere shortening (versus maintenance/growth) over the 2-year study were more than 6 (OR  = 6.26, 95% CI  = 1.02, 38.49) times higher than a non-carrier, adjusting for established risk factors and potential confounds. Despite the high-functioning, healthy mid-life status of study participants, APOE-ε4 carriers had marked telomere attrition during the 2-year study window, the equivalent of approximately one decade of additional aging compared to non-carriers. Further analyses revealed a modulatory effect of hormone therapy on the association between APOE status and telomere attrition. APOE-ε4 carriers who went off their HT regimen exhibited TL shortening, as predicted for the at-risk population. APOE-ε4 carriers who remained on HT, however, did not exhibit comparable signs of cell aging. The opposite pattern was found in non-carriers. The results suggest that hormone use might buffer against accelerated cell aging in mid-life women at risk for dementia. Importantly, for non-carrier women there was no evidence that HT conferred protective effects on telomere dynamics.", "link"=>"http://www.mendeley.com/research/accelerated-cell-aging-female-apoe%CE%B54-carriers-implications-hormone-therapy", "reader_count"=>44, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>7, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>6, "Student > Bachelor"=>5, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>2, "Researcher"=>7, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>1, "Student > Master"=>5, "Other"=>6, "Student > Bachelor"=>5, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>18, "Medicine and Dentistry"=>6, "Neuroscience"=>5, "Psychology"=>8, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Neuroscience"=>{"Neuroscience"=>5}, "Social Sciences"=>{"Social Sciences"=>1}, "Psychology"=>{"Psychology"=>8}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>18}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>4}}, "reader_count_by_country"=>{"United States"=>4, "Sri Lanka"=>1, "Spain"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/488865"], "description"=>"<p>Dot plot illustrating age-adjusted change in leukocyte telomere length (TL) in carriers of the APOE-ε4 risk allele and non-carrier controls. APOE-ε4 carriers had significantly greater age-adjusted LTL shortening over the 2 year study period than non-carrier control participants [<i>F</i>(1,39) 4.89, <i>p</i> = .03].</p>", "links"=>[], "tags"=>["genotype", "telomere"], "article_id"=>159379, "categories"=>["Biochemistry", "Cell Biology", "Biotechnology", "Neuroscience"], "users"=>["Emily G. Jacobs", "Candyce Kroenke", "Jue Lin", "Elissa S. Epel", "Heather A. Kenna", "Elizabeth H. Blackburn", "Natalie L. Rasgon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0054713.g001", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_APOE_949_4_genotype_and_telomere_attrition_/159379", "title"=>"APOE-ε4 genotype and telomere attrition.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 15:22:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/489007"], "description"=>"<p>Values represent mean (SD) or % as noted.</p>*<p>p<0.05.</p>", "links"=>[], "tags"=>["ht"], "article_id"=>159524, "categories"=>["Biochemistry", "Cell Biology", "Biotechnology", "Neuroscience"], "users"=>["Emily G. Jacobs", "Candyce Kroenke", "Jue Lin", "Elissa S. Epel", "Heather A. Kenna", "Elizabeth H. Blackburn", "Natalie L. Rasgon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0054713.t001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characteristics_of_the_study_sample_by_HT_randomization_/159524", "title"=>"Characteristics of the study sample by HT randomization.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 15:23:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/488912"], "description"=>"<p>Initial evidence that the impact of the APOE-ε4 risk allele on cell aging is modulated by HT use in mid-life women. Among women who were randomized to stay on HT (n = 26) for the two year study period, no significant difference in TL attrition was detected between ε4-carriers and non-carriers. Among women who went off HT (n = 16), those carrying the risk allele exhibited telomere shortening, while non-carriers exhibited telomere maintenance/growth. Values represent mean TL change (base pairs) adjusted for study covariates. Error bars represent S.E.M, ** p≤.005.</p>", "links"=>[], "tags"=>["telomere"], "article_id"=>159433, "categories"=>["Biochemistry", "Cell Biology", "Biotechnology", "Neuroscience"], "users"=>["Emily G. Jacobs", "Candyce Kroenke", "Jue Lin", "Elissa S. Epel", "Heather A. Kenna", "Elizabeth H. Blackburn", "Natalie L. Rasgon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0054713.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impact_of_hormone_therapy_on_telomere_dynamics_is_APOE_dependent_/159433", "title"=>"Impact of hormone therapy on telomere dynamics is APOE-dependent.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-19 15:23:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/488964"], "description"=>"*<p>p<0.05.</p>†<p>Reference group.</p><p>Adjusted for age, education and baseline TL.</p><p>Note: R<sup>2</sup> = .30 (Cox & Snell). Model χ<sup>2</sup>(1)  = 14.81, p = .011.</p><p>Non-carrier, Carrier (n = 24, 18) On, Off HT (n = 26, 16).</p>", "links"=>[], "tags"=>["ratios", "ci", "predictors", "telomere"], "article_id"=>159479, "categories"=>["Biochemistry", "Cell Biology", "Biotechnology", "Neuroscience"], "users"=>["Emily G. Jacobs", "Candyce Kroenke", "Jue Lin", "Elissa S. Epel", "Heather A. Kenna", "Elizabeth H. Blackburn", "Natalie L. Rasgon"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0054713.t002", "stats"=>{"downloads"=>4, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Odds_ratios_and_95_CI_for_predictors_of_telomere_shortening_/159479", "title"=>"Odds ratios and 95% CI for predictors of telomere shortening.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-19 15:23:32"}

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  • {"unique-ip"=>"18", "full-text"=>"36", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
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  • {"unique-ip"=>"14", "full-text"=>"16", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
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  • {"unique-ip"=>"14", "full-text"=>"24", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"18", "full-text"=>"24", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"15", "full-text"=>"22", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"17", "full-text"=>"24", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"23", "full-text"=>"40", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"11", "full-text"=>"23", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"16", "full-text"=>"22", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}

Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[272, 472, 600, 713, 815, 911, 1004, 1094, 1185, 1273, 1358, 1441]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[264, 460, 584, 692, 794, 887, 978, 1067, 1154, 1241, 1328, 1408, 1474]}, {"subject_area"=>"/Medicine and health sciences/Mental health and psychiatry", "average_usage"=>[282, 468, 596, 706, 804, 895, 1000, 1081, 1175, 1272, 1356, 1445, 1531]}, {"subject_area"=>"/Medicine and health sciences/Neurology", "average_usage"=>[271, 485, 617, 733, 835, 933, 1026, 1115, 1207, 1294, 1386, 1475, 1543]}]}

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