title: Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans.
abstract: The nematode Caenorhabditis elegans is an important model for studying the genetics of ageing, with over 50 life-extension mutations known so far. However, little is known about the pathobiology of ageing in this species, limiting attempts to connect genotype with senescent phenotype. Using ultrastructural analysis and visualization of specific cell types with green fluorescent protein, we examined cell integrity in different tissues as the animal ages. We report remarkable preservation of the nervous system, even in advanced old age, in contrast to a gradual, progressive deterioration of muscle, resembling human sarcopenia. The age-1(hx546) mutation, which extends lifespan by 60-100%, delayed some, but not all, cellular biomarkers of ageing. Strikingly, we found strong evidence that stochastic as well as genetic factors are significant in C. elegans ageing, with extensive variability both among same-age animals and between cells of the same type within individuals.
authors.affiliation: Department of Molecular Biology and Biochemistry, Rutgers, The State University of New Jersey, A232 Nelson Biological Laboratories, 604 Allison Road, Piscataway, New Jersey 08854, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Herndon
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schmeissner
authors.forename: Justyna M
authors.initials: JM
authors.lastname: Dudaronek
authors.forename: Paula A
authors.initials: PA
authors.lastname: Brown
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Listner
authors.forename: Yuko
authors.initials: Y
authors.lastname: Sakano
authors.forename: Marie C
authors.initials: MC
authors.lastname: Paupard
authors.forename: David H
authors.initials: DH
authors.lastname: Hall
authors.forename: Monica
authors.initials: M
authors.lastname: Driscoll
mesh_terms: D000375:Aging / Q000235:genetics / Q000473:pathology / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D017238:Genes, Helminth; D006801:Humans; D008124:Locomotion / Q000502:physiology; D008136:Longevity / Q000235:genetics / Q000502:physiology; D009132:Muscles / Q000166:cytology / Q000473:pathology / Q000502:physiology; D009154:Mutation / Q000235:genetics; D009424:Nervous System Physiological Phenomena; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009928:Organ Specificity; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases; D012098:Reproduction; D013269:Stochastic Processes; D013997:Time Factors
chemical_list: D015415:Biomarkers; D029742:Caenorhabditis elegans Proteins; D019869:Phosphatidylinositol 3-Kinases; C100662:AGE-1 protein, C elegans