e1bf427ca7f09ef68854aafdc3c504ff animals-15-00521.pdf 9d1d45fc74cb40a8bb9feab2e188569c8c4491ae animals-15-00521.pdf c9d830b4077169c1135b9edf702160d80b01377b7a856caf2ad8a2badadf5dbf animals-15-00521.pdf Title: Phenotypical, Behavioral, and Systemic Hallmarks in End-Point Mouse Scenarios Subject: The state of frailty is a clinical–biological syndrome that affects the older population with a higher risk of functional dependence. Animal models can provide a tool to study this complex scenario. In the present work, we analyzed the physical and behavioral hallmarks of end-point status in 16-month-old mice (C57BL/6J) according to animal welfare regulations compared to age-matched counterparts with normal aging. A group of 6-month-old mice was added to control for age bias. First, we identified ‘structural kyphosis’ (visible and unmodifiable deformation in locomotion) correlated with piloerection as the hallmarks of the physical frailty phenotype compared to the ‘postural kyphosis’ (adjustment to counteract increased visceral volume but attenuated during locomotion) of old mice with normal aging. Alopecia (barbering) was presented in both old groups. Normal levels of exploratory activity in the corner test for neophobia and triceps surae muscle weight but an increased latency of rearing indicated the poorest emotional phenotype, with a possible contribution of structural kyphosis. The presence of hepatomegaly and splenomegaly counteracted the significant WAT loss commonly associated with end-of-life traits, which should have a normal body weight but preserved muscle mass.20pt Keywords: end-point; animal welfare; euthanasia; bodyweight; sarcopenia; C57BL/6J mice Author: Lidia Castillo-Mariqueo, Daniel Alveal-Mellado and Lydia Giménez-Llort Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Wed Feb 12 11:26:51 2025 CET ModDate: Wed Feb 12 11:32:06 2025 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1740141 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- QKZKVH+VnURWPalladioL Type 1 Custom yes yes yes 10 0 WRNZFQ+URWPalladioL-Roma Type 1 Custom yes yes yes 16 0 TTVRDP+URWPalladioL-Bold Type 1 Custom yes yes yes 22 0 WREOIC+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 HOOEPH+CMSY10 Type 1 Builtin yes yes yes 32 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes yes 64 0 HYYHEA+CMBSY10 Type 1 Builtin yes yes yes 72 0 DDHBFN+PalatinoLinotype,Bold CID TrueType Identity-H yes yes yes 80 0 DDHGFK+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 86 0 DDHBGO+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 89 0 DDHBGP+PalatinoLinotype CID TrueType Identity-H yes yes yes 92 0 DDHBHA+PalatinoLinotype TrueType WinAnsi yes yes no 98 0 DDHBHC+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 101 0 DDHGEI+Arial,Bold CID TrueType Identity-H yes yes yes 104 0 BKBIJJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 117 0 BKBIJK+PalatinoLinotype CID TrueType Identity-H yes yes yes 120 0 BKBIJL+PalatinoLinotype TrueType WinAnsi yes yes no 126 0 BKBIJN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 129 0 BKBJAN+PalatinoLinotype TrueType MacRoman yes yes no 132 0 BKBIJJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 143 0 BKBIJK+PalatinoLinotype CID TrueType Identity-H yes yes yes 146 0 BKBIJL+PalatinoLinotype TrueType WinAnsi yes yes no 152 0 BKBIJN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 155 0 BKBJAN+PalatinoLinotype TrueType MacRoman yes yes no 158 0 BKBIJJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 169 0 BKBIJL+PalatinoLinotype TrueType WinAnsi yes yes no 172 0 BKBIJN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 175 0 BKBJAN+PalatinoLinotype TrueType MacRoman yes yes no 178 0 BKBIJJ+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 188 0 BKBIJL+PalatinoLinotype TrueType WinAnsi yes yes no 191 0 BKBIJN+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 194 0 BKBJAN+PalatinoLinotype TrueType MacRoman yes yes no 197 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-04-03 02:10:00 CEST RepresentationInformation: animals-15-00521.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-04-02 13:21:09 CEST Size: 1740141 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 415 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Animals Destination: subsection.2.1 Item: Title: Experimental Design Destination: subsection.2.2 Item: Title: Physical Frailty Phenotype, Geotaxis and Exploratory Activity Destination: subsection.2.3 Item: Title: Hepatic, Splenic, and WAT Indexes Related to Sarcopenia Destination: subsection.2.4 Item: Title: Statistics Destination: subsection.2.5 Item: Title: Results Destination: section.3 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.6 Info: Title: Phenotypical, Behavioral, and Systemic Hallmarks in End-Point Mouse Scenarios Author: Lidia Castillo-Mariqueo, Daniel Alveal-Mellado and Lydia Giménez-Llort Subject: The state of frailty is a clinical biological syndrome that affects the older population with a higher risk of functional dependence. Animal models can provide a tool to study this complex scenario. In the present work, we analyzed the physical and behavioral hallmarks of end-point status in 16-month-old mice (C57BL/6J) according to animal welfare regulations compared to age-matched counterparts with normal aging. A group of 6-month-old mice was added to control for age bias. First, we identified ‘structural kyphosis’ (visible and unmodifiable deformation in locomotion) correlated with piloerection as the hallmarks of the physical frailty phenotype compared to the ‘postural kyphosis’ (adjustment to counteract increased visceral volume but attenuated during locomotion) of old mice with normal aging. Alopecia (barbering) was presented in both old groups. Normal levels of exploratory activity in the corner test for neophobia and triceps surae muscle weight but an increased latency of rearing indicated the poorest emotional phenotype, with a possible contribution of structural kyphosis. 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