title: Inbred mouse strains reveal biomarkers that are pro-longevity, antilongevity or role switching.
abstract: Traditionally, biomarkers of aging are classified as either pro-longevity or antilongevity. Using longitudinal data sets from the large-scale inbred mouse strain study at the Jackson Laboratory Nathan Shock Center, we describe a protocol to identify two kinds of biomarkers: those with prognostic implication for lifespan and those with longitudinal evidence. Our protocol also identifies biomarkers for which, at first sight, there is conflicting evidence. Conflict resolution is possible by postulating a role switch. In these cases, high biomarker values are, for example, antilongevity in early life and pro-longevity in later life. Role-switching biomarkers correspond to features that must, for example, be minimized early, but maximized later, for optimal longevity. The clear-cut pro-longevity biomarkers we found reflect anti-inflammatory, anti-immunosenescent or anti-anaemic mechanisms, whereas clear-cut antilongevity biomarkers reflect inflammatory mechanisms. Many highly significant blood biomarkers relate to immune system features, indicating a shift from adaptive to innate processes, whereas most role-switching biomarkers relate to blood serum features and whole-body phenotypes. Our biomarker classification approach is applicable to any combination of longitudinal studies with life expectancy data, and it provides insights beyond a simplified scheme of biomarkers for long or short lifespan.
authors.affiliation: Institute for Biostatistics and Informatics in Medicine und Ageing Research, Rostock University Medical Center, Rostock, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Moeller
authors.forename: Misa
authors.initials: M
authors.lastname: Hirose
authors.forename: Sarah
authors.initials: S
authors.lastname: Mueller
authors.forename: Catrin
authors.initials: C
authors.lastname: Roolf
authors.forename: Simone
authors.initials: S
authors.lastname: Baltrusch
authors.forename: Saleh
authors.initials: S
authors.lastname: Ibrahim
authors.forename: Christian
authors.initials: C
authors.lastname: Junghanss
authors.forename: Olaf
authors.initials: O
authors.lastname: Wolkenhauer
authors.forename: Robert
authors.initials: R
authors.lastname: Jaster
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Köhling
authors.forename: Manfred
authors.initials: M
authors.lastname: Kunz
authors.forename: Markus
authors.initials: M
authors.lastname: Tiedge
authors.forename: Paul N
authors.initials: PN
authors.lastname: Schofield
authors.forename: Georg
authors.initials: G
authors.lastname: Fuellen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D001772:Blood Cell Count; D005260:Female; D008136:Longevity / Q000502:physiology*; D008297:Male; D008815:Mice, Inbred Strains; D016016:Proportional Hazards Models
chemical_list: D015415:Biomarkers
keywords: aging; anti-aging; inflammation; lifespan; longevity; mice; senescence