Aging Aggravates Cachexia in Tumor-Bearing Mice

Background: Cancer is primarily a disease of high age in humans, yet most mouse studies on cancer cachexia are conducted using young adolescent mice. Given that metabolism and muscle function change with age, we hypothesized that aging may affect cachexia progression in mouse models. Methods: We com...

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Main Authors: Julia Geppert, Alina A. Walth, Raúl Terrón Expósito, Doris Kaltenecker, Pauline Morigny, Juliano Machado, Maike Becker, Estefania Simoes, Joanna D. C. C. Lima, Carolin Daniel, Mauricio Berriel Diaz, Stephan Herzig, Marilia Seelaender, Maria Rohm
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:Cancers
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Online Access:https://www.mdpi.com/2072-6694/14/1/90
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author Julia Geppert
Alina A. Walth
Raúl Terrón Expósito
Doris Kaltenecker
Pauline Morigny
Juliano Machado
Maike Becker
Estefania Simoes
Joanna D. C. C. Lima
Carolin Daniel
Mauricio Berriel Diaz
Stephan Herzig
Marilia Seelaender
Maria Rohm
author_facet Julia Geppert
Alina A. Walth
Raúl Terrón Expósito
Doris Kaltenecker
Pauline Morigny
Juliano Machado
Maike Becker
Estefania Simoes
Joanna D. C. C. Lima
Carolin Daniel
Mauricio Berriel Diaz
Stephan Herzig
Marilia Seelaender
Maria Rohm
author_sort Julia Geppert
collection DOAJ
description Background: Cancer is primarily a disease of high age in humans, yet most mouse studies on cancer cachexia are conducted using young adolescent mice. Given that metabolism and muscle function change with age, we hypothesized that aging may affect cachexia progression in mouse models. Methods: We compare tumor and cachexia development in young and old mice of three different strains (C57BL/6J, C57BL/6N, BALB/c) and with two different tumor cell lines (Lewis Lung Cancer, Colon26). Tumor size, body and organ weights, fiber cross-sectional area, circulating cachexia biomarkers, and molecular markers of muscle atrophy and adipose tissue wasting are shown. We correlate inflammatory markers and body weight dependent on age in patients with cancer. Results: We note fundamental differences between mouse strains. Aging aggravates weight loss in LLC-injected C57BL/6J mice, drives it in C57BL/6N mice, and does not influence weight loss in C26-injected BALB/c mice. Glucose tolerance is unchanged in cachectic young and old mice. The stress marker GDF15 is elevated in cachectic BALB/c mice independent of age and increased in old C57BL/6N and J mice. Inflammatory markers correlate significantly with weight loss only in young mice and patients. Conclusions: Aging affects cachexia development and progression in mice in a strain-dependent manner and influences the inflammatory profile in both mice and patients. Age is an important factor to consider for future cachexia studies.
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spelling doaj.art-6b9e04cf12984e39b5d7a6d39c2226672023-11-23T11:15:53ZengMDPI AGCancers2072-66942021-12-011419010.3390/cancers14010090Aging Aggravates Cachexia in Tumor-Bearing MiceJulia Geppert0Alina A. Walth1Raúl Terrón Expósito2Doris Kaltenecker3Pauline Morigny4Juliano Machado5Maike Becker6Estefania Simoes7Joanna D. C. C. Lima8Carolin Daniel9Mauricio Berriel Diaz10Stephan Herzig11Marilia Seelaender12Maria Rohm13Institute for Diabetes and Cancer, Helmholtz Center Munich, 85764 Neuherberg, GermanyInstitute for Diabetes and Cancer, Helmholtz Center Munich, 85764 Neuherberg, GermanyInstitute for Diabetes and Cancer, Helmholtz Center Munich, 85764 Neuherberg, GermanyInstitute for Diabetes and Cancer, Helmholtz Center Munich, 85764 Neuherberg, GermanyInstitute for Diabetes and Cancer, Helmholtz Center Munich, 85764 Neuherberg, GermanyInstitute for Diabetes and Cancer, Helmholtz Center Munich, 85764 Neuherberg, GermanyGerman Center for Diabetes Research (DZD), 85764 Neuherberg, GermanyInstitute for Diabetes and Cancer, Helmholtz Center Munich, 85764 Neuherberg, GermanyDepartment of Surgery and LIM 26, Faculdade de Medicina, University of Sao Paulo, Sao Paulo 01246-903, BrazilGerman Center for Diabetes Research (DZD), 85764 Neuherberg, GermanyInstitute for Diabetes and Cancer, Helmholtz Center Munich, 85764 Neuherberg, GermanyInstitute for Diabetes and Cancer, Helmholtz Center Munich, 85764 Neuherberg, GermanyDepartment of Surgery and LIM 26, Faculdade de Medicina, University of Sao Paulo, Sao Paulo 01246-903, BrazilInstitute for Diabetes and Cancer, Helmholtz Center Munich, 85764 Neuherberg, GermanyBackground: Cancer is primarily a disease of high age in humans, yet most mouse studies on cancer cachexia are conducted using young adolescent mice. Given that metabolism and muscle function change with age, we hypothesized that aging may affect cachexia progression in mouse models. Methods: We compare tumor and cachexia development in young and old mice of three different strains (C57BL/6J, C57BL/6N, BALB/c) and with two different tumor cell lines (Lewis Lung Cancer, Colon26). Tumor size, body and organ weights, fiber cross-sectional area, circulating cachexia biomarkers, and molecular markers of muscle atrophy and adipose tissue wasting are shown. We correlate inflammatory markers and body weight dependent on age in patients with cancer. Results: We note fundamental differences between mouse strains. Aging aggravates weight loss in LLC-injected C57BL/6J mice, drives it in C57BL/6N mice, and does not influence weight loss in C26-injected BALB/c mice. Glucose tolerance is unchanged in cachectic young and old mice. The stress marker GDF15 is elevated in cachectic BALB/c mice independent of age and increased in old C57BL/6N and J mice. Inflammatory markers correlate significantly with weight loss only in young mice and patients. Conclusions: Aging affects cachexia development and progression in mice in a strain-dependent manner and influences the inflammatory profile in both mice and patients. Age is an important factor to consider for future cachexia studies.https://www.mdpi.com/2072-6694/14/1/90agingcachexiacancermouse models
spellingShingle Julia Geppert
Alina A. Walth
Raúl Terrón Expósito
Doris Kaltenecker
Pauline Morigny
Juliano Machado
Maike Becker
Estefania Simoes
Joanna D. C. C. Lima
Carolin Daniel
Mauricio Berriel Diaz
Stephan Herzig
Marilia Seelaender
Maria Rohm
Aging Aggravates Cachexia in Tumor-Bearing Mice
Cancers
aging
cachexia
cancer
mouse models
title Aging Aggravates Cachexia in Tumor-Bearing Mice
title_full Aging Aggravates Cachexia in Tumor-Bearing Mice
title_fullStr Aging Aggravates Cachexia in Tumor-Bearing Mice
title_full_unstemmed Aging Aggravates Cachexia in Tumor-Bearing Mice
title_short Aging Aggravates Cachexia in Tumor-Bearing Mice
title_sort aging aggravates cachexia in tumor bearing mice
topic aging
cachexia
cancer
mouse models
url https://www.mdpi.com/2072-6694/14/1/90
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