title: Cell-associated pentosidine as a marker of aging in human diploid cells in vitro and in vivo.
abstract: Cellular aging is characterized by alterations at both the morphological and molecular levels, some of which are decreased mitotic rate, increased cytoplasmic vacuolization, and changes in intrinsic cellular constituents (Stanulis-Praeger, 1987. Mech. Ageing Dev. 38, 1-48). In the present investigation, glycoxidation is studied as a marker for cellular aging by measuring cell-associated pentosidine levels in human skin fibroblasts as a function of replicative life span and in human peripheral blood T lymphocytes as a function of chronological age. Fibroblasts were isolated from culture by detachment/centrifugation while lymphocytes were isolated from blood by a Ficoll-Paque/Lympho-Kwik T-Cell Prep technique. Pentosidine levels were measured in acid-hydrolyzed cell pellet suspensions by high-pressure liquid chromatography. Results show that pentosidine was detected in early and late cultured reticular and papillary fibroblasts. Pentosidine, expressed as either protein, DNA, or cell number, significantly (P < 0.0006) increased with in vitro passage and was significantly (P < 0.01) related to cell proliferation as measured by cell density and cell doublings per day during culture. Cell-associated pentosidine was measured in T lymphocytes isolated from healthy, diabetic, and uremic individuals. In healthy controls, levels significantly (P < 0.0003) increased with age. In uremic individuals, a large variation was observed with many values above the 95% confidence intervals determined for controls. Since a previous study showed that plasma pentosidine in healthy subjects does not increase with age, these results suggest that cellular turnover perhaps coupled to a deterioration in cellular anti-glycoxidation defensive mechanisms play a substantial role in explaining increased pentosidine concentrations during cellular aging.
authors.affiliation: Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Sell
authors.forename: M
authors.initials: M
authors.lastname: Primc
authors.forename: I A
authors.initials: IA
authors.lastname: Schafer
authors.forename: M
authors.initials: M
authors.lastname: Kovach
authors.forename: M A
authors.initials: MA
authors.lastname: Weiss
authors.forename: V M
authors.initials: VM
authors.lastname: Monnier
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D015415:Biomarkers; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D004171:Diploidy; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; D001120:Arginine; C062187:pentosidine; D008239:Lysine