PMID- 36463290 OWN - NLM STAT- MEDLINE DCOM- 20221206 LR - 20230618 IS - 2052-4463 (Electronic) IS - 2052-4463 (Linking) VI - 9 IP - 1 DP - 2022 Dec 3 TI - A multi-omics longitudinal aging dataset in primary human fibroblasts with mitochondrial perturbations. PG - 751 LID - 10.1038/s41597-022-01852-y [doi] LID - 751 AB - Aging is a process of progressive change. To develop biological models of aging, longitudinal datasets with high temporal resolution are needed. Here we report a multi-omics longitudinal dataset for cultured primary human fibroblasts measured across their replicative lifespans. Fibroblasts were sourced from both healthy donors (n = 6) and individuals with lifespan-shortening mitochondrial disease (n = 3). The dataset includes cytological, bioenergetic, DNA methylation, gene expression, secreted proteins, mitochondrial DNA copy number and mutations, cell-free DNA, telomere length, and whole-genome sequencing data. This dataset enables the bridging of mechanistic processes of aging as outlined by the "hallmarks of aging", with the descriptive characterization of aging such as epigenetic age clocks. Here we focus on bridging the gap for the hallmark mitochondrial metabolism. Our dataset includes measurement of healthy cells, and cells subjected to over a dozen experimental manipulations targeting oxidative phosphorylation (OxPhos), glycolysis, and glucocorticoid signaling, among others. These experiments provide opportunities to test how cellular energetics affect the biology of cellular aging. All data are publicly available at our webtool: https://columbia-picard.shinyapps.io/shinyapp-Lifespan_Study/. CI - (c) 2022. The Author(s). FAU - Sturm, Gabriel AU - Sturm G AUID- ORCID: 0000-0002-7280-4310 AD - Division of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA. AD - Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA. FAU - Monzel, Anna S AU - Monzel AS AD - Division of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA. FAU - Karan, Kalpita R AU - Karan KR AD - Division of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA. FAU - Michelson, Jeremy AU - Michelson J AD - Division of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA. FAU - Ware, Sarah A AU - Ware SA AD - University of Pittsburgh, School of Medicine, Division of Cardiology, Center for Metabolism and Mitochondrial Medicine and Vascular Medicine Institute, Pittsburgh, PA, USA. FAU - Cardenas, Andres AU - Cardenas A AUID- ORCID: 0000-0003-2284-3298 AD - Department of Epidemiology and Population Health, Stanford University, Stanford, CA, 94305, USA. FAU - Lin, Jue AU - Lin J AD - Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA. FAU - Bris, Celine AU - Bris C AD - UMR CNRS 6015, INSERM U1083, MITOVASC, SFR ICAT, Universite d'Angers, Angers, F-49000, France. AD - Department of Genetics, CHU Angers, Angers, F-49000, France. FAU - Santhanam, Balaji AU - Santhanam B AD - Department of Biological Sciences, Columbia University, New York, NY, USA. FAU - Murphy, Michael P AU - Murphy MP AUID- ORCID: 0000-0003-1115-9618 AD - MRC-Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK. FAU - Levine, Morgan E AU - Levine ME AD - Department of Pathology, Yale University School of Medicine, New Haven, CT, 06520, USA. AD - Altos Labs, San Diego, USA. FAU - Horvath, Steve AU - Horvath S AUID- ORCID: 0000-0002-4110-3589 AD - Altos Labs, San Diego, USA. AD - Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA. FAU - Belsky, Daniel W AU - Belsky DW AD - Department of Epidemiology & Butler Columbia Aging Center, Columbia University Mailman School of Public Health, New York, NY, USA. FAU - Wang, Shuang AU - Wang S AD - Department of Biostatistics, Columbia University Irving Medical Center, New York, NY, USA. FAU - Procaccio, Vincent AU - Procaccio V AD - UMR CNRS 6015, INSERM U1083, MITOVASC, SFR ICAT, Universite d'Angers, Angers, F-49000, France. AD - Department of Genetics, CHU Angers, Angers, F-49000, France. FAU - Kaufman, Brett A AU - Kaufman BA AUID- ORCID: 0000-0003-4767-4937 AD - University of Pittsburgh, School of Medicine, Division of Cardiology, Center for Metabolism and Mitochondrial Medicine and Vascular Medicine Institute, Pittsburgh, PA, USA. FAU - Hirano, Michio AU - Hirano M AD - Merritt Center and Columbia Translational Neuroscience Initiative, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA. FAU - Picard, Martin AU - Picard M AD - Division of Behavioral Medicine, Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA. martin.picard@columbia.edu. AD - Merritt Center and Columbia Translational Neuroscience Initiative, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA. martin.picard@columbia.edu. AD - New York State Psychiatric Institute, New York, NY, USA. martin.picard@columbia.edu. LA - eng GR - R01 AG066828/AG/NIA NIH HHS/United States PT - Journal Article DEP - 20221203 PL - England TA - Sci Data JT - Scientific data JID - 101640192 SB - IM MH - Humans MH - *Aging MH - *Fibroblasts MH - Longevity MH - Cellular Senescence MH - Glycolysis PMC - PMC9719499 COIS- The authors declare no competing interest. EDAT- 2022/12/04 06:00 MHDA- 2022/12/07 06:00 PMCR- 2022/12/03 CRDT- 2022/12/03 23:35 PHST- 2022/01/27 00:00 [received] PHST- 2022/11/17 00:00 [accepted] PHST- 2022/12/03 23:35 [entrez] PHST- 2022/12/04 06:00 [pubmed] PHST- 2022/12/07 06:00 [medline] PHST- 2022/12/03 00:00 [pmc-release] AID - 10.1038/s41597-022-01852-y [pii] AID - 1852 [pii] AID - 10.1038/s41597-022-01852-y [doi] PST - epublish SO - Sci Data. 2022 Dec 3;9(1):751. doi: 10.1038/s41597-022-01852-y.