{"doi":"10.1007/s11764-024-01591-6","title":"Determining the relationship of p16INK4a and additional molecular markers of aging with clinical frailty in hematologic malignancy","abstract":"<jats:title>Abstract</jats:title><jats:sec>\n                <jats:title>Purpose</jats:title>\n                <jats:p>Older adults with hematologic malignancies (HM) have unique challenges due to age and fitness. The primary aim of this pilot study was to benchmark the ability of multiple biomarkers of aging (p16, epigenetic clocks, T cell gene expression profiles, and T cell receptor excision circles (TREC) to identify frailty as measured by a clinical impairment index (I<jats:sup>2</jats:sup>) in patients with HM.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Methods</jats:title>\n                <jats:p>70 patients newly diagnosed with HM had peripheral blood T lymphocytes (PBTL) analyzed for p16<jats:sup>INK4a</jats:sup> expression using the OSU_Senescence Nanostring CodeSet. PBTL epigenetic age was measured using 7 epigenetic clocks, and TREC were quantified by qRT-PCR. A composite clinical impairment index (I<jats:sup>2</jats:sup>) was generated by combining values from 11 geriatric metrics (Independent Activities of Daily Living (iADL), physical health score, Short Physical Performance Battery (SPPB), Body Mass Index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status, self-reported KPS, Blessed Orientation Memory Concentration (BOMC), polypharmacy, Mental Health Inventory (MHI)-17, Medical Outcomes Study (MOS) subscales). Clinical frailty was defined as a score of 7 or greater on the I<jats:sup>2</jats:sup>.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Results</jats:title>\n                <jats:p>Age-adjusted p16<jats:sup>INK4a</jats:sup> was similar in newly diagnosed patients and healthy controls (<jats:italic>p</jats:italic> &gt; 0.1). PBTL p16<jats:sup>INK4a</jats:sup> levels correlated positively with the Hannum [r = 0.35, 95% CI (0.09–0.75); p adj. = 0.04] and PhenoAge [r = 0.37, 95% CI (0.11–0.59); p adj. = 0.04] epigenetic clocks. The discrimination ability of the I<jats:sup>2</jats:sup> model was calculated using the area under the receiver operating characteristic curve (AUC). After adjusting for chronologic age and disease group, baseline p16<jats:sup>INK4a</jats:sup> [AUC = 0.76, 95% CI (0.56–0.98); <jats:italic>p</jats:italic> = 0.01], Hannum [AUC = 0.70, 95% CI (0.54–0.85); <jats:italic>p</jats:italic> = 0.01], PhenoAge [AUC = 0.71, 95% CI (0.55–0.86); <jats:italic>p</jats:italic> = 0.01], and DunedinPACE [AUC = 0.73, 95% CI (0.57–0.88); <jats:italic>p</jats:italic> =  &lt; 0.01] measures showed the greatest potential to identify clinical frailty using the I<jats:sup>2</jats:sup>.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Conclusions</jats:title>\n                <jats:p>Our pilot data suggest that multiple blood-based aging biomarkers have potential to identify frailty in older adults with HM.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Implications for Cancer Survivors</jats:title>\n                <jats:p>We developed the I<jats:sup>2</jats:sup> index to quantify impairments across geriatric domains and discovered that PBTL p16, Hannum, PhenoAge, and DunedinPACE are promising indicators of frailty in HM.</jats:p>\n              </jats:sec>","journal":"Journal of Cancer Survivorship","year":2024,"id":647968,"datarank":0.4782174469187921,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"self_citation_contribution":0.3596842909197557,"citation_network_contribution":0.11853315599903644,"self_endowment_contribution":0.3596842909197557,"citer_contribution":0.11853315599903644,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":7,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":846448,"name":"Mohamed I. Elsaid","orcid":"0000-0001-7963-2438","position":1,"is_corresponding":false},{"id":1638985,"name":"Jennifer Woyach","orcid":null,"position":2,"is_corresponding":false},{"id":1681194,"name":"Nowshin Islam","orcid":null,"position":3,"is_corresponding":false},{"id":1359944,"name":"Noah Lepola","orcid":null,"position":4,"is_corresponding":false},{"id":1106650,"name":"Jazmin Urrutia","orcid":"0000-0002-0434-4308","position":5,"is_corresponding":false},{"id":395866,"name":"Lisa M. Christian","orcid":"0000-0001-5571-050X","position":6,"is_corresponding":false},{"id":565244,"name":"Carolyn Presley","orcid":null,"position":7,"is_corresponding":false},{"id":1681189,"name":"Alice Mims","orcid":null,"position":8,"is_corresponding":false},{"id":233166,"name":"Christin E. Burd","orcid":"0000-0002-7919-3954","position":9,"is_corresponding":false},{"id":1590779,"name":"Ashley E. Rosko","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Determining the relationship of p16INK4a and additional molecular markers of aging with clinical frailty in hematologic malignancy","abstract":"<jats:title>Abstract</jats:title><jats:sec>\n                <jats:title>Purpose</jats:title>\n                <jats:p>Older adults with hematologic malignancies (HM) have unique challenges due to age and fitness. The primary aim of this pilot study was to benchmark the ability of multiple biomarkers of aging (p16, epigenetic clocks, T cell gene expression profiles, and T cell receptor excision circles (TREC) to identify frailty as measured by a clinical impairment index (I<jats:sup>2</jats:sup>) in patients with HM.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Methods</jats:title>\n                <jats:p>70 patients newly diagnosed with HM had peripheral blood T lymphocytes (PBTL) analyzed for p16<jats:sup>INK4a</jats:sup> expression using the OSU_Senescence Nanostring CodeSet. PBTL epigenetic age was measured using 7 epigenetic clocks, and TREC were quantified by qRT-PCR. A composite clinical impairment index (I<jats:sup>2</jats:sup>) was generated by combining values from 11 geriatric metrics (Independent Activities of Daily Living (iADL), physical health score, Short Physical Performance Battery (SPPB), Body Mass Index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status, self-reported KPS, Blessed Orientation Memory Concentration (BOMC), polypharmacy, Mental Health Inventory (MHI)-17, Medical Outcomes Study (MOS) subscales). Clinical frailty was defined as a score of 7 or greater on the I<jats:sup>2</jats:sup>.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Results</jats:title>\n                <jats:p>Age-adjusted p16<jats:sup>INK4a</jats:sup> was similar in newly diagnosed patients and healthy controls (<jats:italic>p</jats:italic> &gt; 0.1). PBTL p16<jats:sup>INK4a</jats:sup> levels correlated positively with the Hannum [r = 0.35, 95% CI (0.09–0.75); p adj. = 0.04] and PhenoAge [r = 0.37, 95% CI (0.11–0.59); p adj. = 0.04] epigenetic clocks. The discrimination ability of the I<jats:sup>2</jats:sup> model was calculated using the area under the receiver operating characteristic curve (AUC). After adjusting for chronologic age and disease group, baseline p16<jats:sup>INK4a</jats:sup> [AUC = 0.76, 95% CI (0.56–0.98); <jats:italic>p</jats:italic> = 0.01], Hannum [AUC = 0.70, 95% CI (0.54–0.85); <jats:italic>p</jats:italic> = 0.01], PhenoAge [AUC = 0.71, 95% CI (0.55–0.86); <jats:italic>p</jats:italic> = 0.01], and DunedinPACE [AUC = 0.73, 95% CI (0.57–0.88); <jats:italic>p</jats:italic> =  &lt; 0.01] measures showed the greatest potential to identify clinical frailty using the I<jats:sup>2</jats:sup>.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Conclusions</jats:title>\n                <jats:p>Our pilot data suggest that multiple blood-based aging biomarkers have potential to identify frailty in older adults with HM.</jats:p>\n              </jats:sec><jats:sec>\n                <jats:title>Implications for Cancer Survivors</jats:title>\n                <jats:p>We developed the I<jats:sup>2</jats:sup> index to quantify impairments across geriatric domains and discovered that PBTL p16, Hannum, PhenoAge, and DunedinPACE are promising indicators of frailty in HM.</jats:p>\n              </jats:sec>","is_dataset_classified":null,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38678524","pmcid":"PMC11324703","openalex_id":"https://openalex.org/W4395955245","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"P30 CA016058","title":null},{"funder_name":"National Institutes of Health","grant_id":"3P30CA016058-15S1","title":"CORE--HORMONE RECEPTOR LABORATORY"}],"total_grants":2,"fwci":2.6344,"citation_percentile":0.89754006,"influential_citations":0,"citation_trend":[{"year":2024,"count":3},{"year":2025,"count":4},{"year":2026,"count":3}],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://link.springer.com/content/pdf/10.1007/s11764-024-01591-6.pdf","host_type":"journal"},{"url":"https://link.springer.com/content/pdf/10.1007/s11764-024-01591-6.pdf","host_type":"publisher"},{"url":"https://link.springer.com/article/10.1007/s11764-024-01591-6/fulltext.html","host_type":"publisher"},{"url":"https://doi.org/10.1007/s11764-024-01591-6","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38678524","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11324703","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11324703/pdf/11764_2024_Article_1591.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11324703","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11324703?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1007/s11764-024-01591-6","host_type":""}],"fields_of_study":["Frailty in Older Adults","Nutrition and Health in Aging","Palliative Care and End-of-Life Issues","0301 basic medicine","0303 health sciences","03 medical and health sciences","Humans","Male","Female","Cyclin-Dependent Kinase Inhibitor p16","Aged","Frailty","Pilot Projects","Hematologic Neoplasms","Aging","Aged, 80 and over","Middle Aged","Biomarkers, Tumor"],"mesh_terms":["Frailty","Aged","Aged, 80 and over","Aging","Female","Humans","Male","Middle Aged","Pilot Projects","Biomarkers, Tumor","Hematologic Neoplasms","Cyclin-Dependent Kinase Inhibitor p16"],"keywords":["Medicine","Polypharmacy","Epigenetics","Internal medicine","Body mass index","Receiver operating characteristic","Oncology","Gerontology","Gene","p16","Frailty","Hematologic Malignancy","Aging Biomarkers","Male","Aged, 80 and over","Aging","Pilot Projects","Middle Aged","Article","Hematologic Neoplasms","Biomarkers, Tumor","Humans","Female","Cyclin-Dependent Kinase Inhibitor p16","Aged"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Peace, Justice and strong institutions"},{"sdg_number":0,"sdg_label":"Reduced inequalities"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T02:05:13.352235Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}