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Association of biological aging with frailty and post-transplant outcomes among adults with cirrhosis

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Abstract

Frailty is classically associated with advanced age but is also an important predictor of clinical outcomes in comparatively young adults with cirrhosis. We examined the association of biological aging with frailty and post-transplant outcomes in a pilot of adults with cirrhosis undergoing liver transplantation (LT). Frailty was measured via the Liver Frailty Index (LFI). The primary epigenetic clock DNA methylation (DNAm) PhenoAge was calculated from banked peripheral blood mononuclear cells; we secondarily explored two first-generation clocks (Hannum; Horvath) and two additional second-generation clocks (GrimAge; GrimAge2). Twelve adults were included: seven frail (LFI ≥ 4.4, mean age 55 years) and five robust (LFI < 3.2, mean age 55 years). Mean PhenoAge age acceleration (AgeAccel) was + 2.5 years (P = 0.23) for frail versus robust subjects. Mean PhenoAge AgeAccel was + 2.7 years (P = 0.19) for subjects who were readmitted or died within 30 days of discharge post-LT versus those without this outcome. When compared with first-generation clocks, the second-generation clocks demonstrated greater average AgeAccel for subjects with frailty or poor post-LT outcomes. Measuring biological age using DNAm-derived epigenetic clocks is feasible in adults undergoing LT. While frail and robust subjects had the same average chronological age, average biological age as measured by second-generation epigenetic clocks tended to be accelerated among those who were frail or experienced a poor post-LT outcome. These results suggest that frailty in these relatively young subjects with cirrhosis may involve similar aging mechanisms as frailty classically observed in chronologically older adults and warrant validation in a larger cohort.

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Funding

This work was supported by a UCSF Bakar Aging Research Institute (BARI) Investigator Award and Buck Institute for Research on Aging intramural funds. Original sample collection was supported in part by R21AG067554.

Dr. LaHue is supported by R03AG074035, Larry L. Hillblom Foundation (A137420), UCSF Claude D. Pepper Older Americans Independence Center P30 AG044281, and the UCSF Bakar Aging Research Institute.

Dr. Furman is supported by Buck Bioinformatics Core, P01AG066591, U54AG075932, P01AI153559.

Dr. Lai is supported by R01AG059183, K24AG080021, P30DK026743.

Dr. Newman is supported by NIH R01AG068025 and Buck Institute Institutional Funds.

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Author notes

  1. Jennifer C. Lai and John C. Newman contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, School of Medicine, University of California, San Francisco, CA, USA

    Sara C. LaHue

  2. Department of Neurology, UCSF Weill Institute for Neurosciences, University of California, 505 Parnassus Ave, Box 0114, San Francisco, CA, 94143, USA

    Sara C. LaHue

  3. Buck Institute for Research On Aging, Novato, CA, USA

    Sara C. LaHue, Matias Fuentealba, Stephanie Roa Diaz, Thelma Garcia, David Furman & John C. Newman

  4. Division of Geriatrics, Department of Medicine, School of Medicine, University of California, San Francisco, CA, USA

    Stephanie Roa Diaz, Thelma Garcia & John C. Newman

  5. Division of Gastroenterology and Hepatology, Department of Medicine, University of California-San Francisco, San Francisco, CA, USA

    Srilakshmi Seetharaman & Jennifer C. Lai

  6. Instituto de Investigaciones en Medicina Traslacional, Universidad Austral, Consejo Nacional de Investigaciones Científicas y Técnicas, 1629, Pilar, Argentina

    David Furman

  7. Stanford 1000 Immunomes Project, Stanford University School of Medicine, Stanford, CA, USA

    David Furman

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LaHue, S.C., Fuentealba, M., Roa Diaz, S. et al. Association of biological aging with frailty and post-transplant outcomes among adults with cirrhosis. GeroScience 46, 3287–3295 (2024). https://doi.org/10.1007/s11357-024-01076-5

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