Sex differences in behavior, immune function, and redox state throughout life, and their effect on the longevity of Swiss mice

Homeostatic systems (nervous, immune, and endocrine) are crucial for maintaining health throughout life and, consequently, relevant for the rate of aging and the longevity achieved. In many species, male and female mammals show different lifespans, attributed to distinct redox states, but it is scar...

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Published in:	Biogerontology (Dordrecht) Vol. 26; no. 6; p. 204
Main Authors:	Félix, Judith, Garrido, Antonio, De la Fuente, Mónica
Format:	Journal Article
Language:	English
Published:	Dordrecht Springer Netherlands 14.11.2025 Springer Nature B.V
Subjects:	Age Age Factors Aging Aging - immunology Animals Anxiety Behavior Behavior, Animal - physiology Biological markers Biomarkers Biomarkers - metabolism Biomedical and Life Sciences Cell Biology Deaths Design of experiments Developmental Biology Estrogens Female Females Function Gender differences Geriatrics/Gerontology Hormones Immune response Immune system Immune System - physiology Immunity, Innate Laboratory animals Leukocytes Life expectancy Life Sciences Longevity Longevity - immunology Longevity - physiology Longitudinal studies Male Males Mental health Mice Motor ability Nutrition research Oxidation-Reduction Oxidative Stress Preservation Redox properties Research Article Research design Sex Characteristics Sex differences Sex Factors Sexes Spain Aging Redox state Sex differences Immunology Behavior Longevity
ISSN:	1389-5729, 1573-6768, 1573-6768
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Abstract	Homeostatic systems (nervous, immune, and endocrine) are crucial for maintaining health throughout life and, consequently, relevant for the rate of aging and the longevity achieved. In many species, male and female mammals show different lifespans, attributed to distinct redox states, but it is scarcely known whether sex differences in the functioning of these systems are involved. This study investigated, in an integrative view, sex differences in the nervous and immune systems of Swiss strain mice by analyzing behavior, immune function, and redox biomarkers across aging, to determine whether possible sex differences in homeostatic systems affect longevity. A longitudinal study was conducted on 20 female and male Swiss mice. At their young (2 mon), adult (7 mon), and old (18 mon) ages, subjects were subjected to a battery of behavioral tests, and peritoneal leukocytes were extracted to assess immune function and redox biomarkers. The natural deaths of animals were recorded for a longevity study. Our results indicate that sexual differences begin at a young age, and several are maintained until old age. Females, in general, show better behavior, immune function, and redox biomarkers, contributing to their higher longevity compared to males. The enhanced longevity in females may be attributable, in part, to the preservation of robust immune competence, with emphasis on innate immune functions and lower oxidative stress. The integration of behavioral and immunological profiles, together with redox biomarkers, underscores the critical importance of incorporating both sex as a biological variable in the design of aging-related research.
AbstractList	Homeostatic systems (nervous, immune, and endocrine) are crucial for maintaining health throughout life and, consequently, relevant for the rate of aging and the longevity achieved. In many species, male and female mammals show different lifespans, attributed to distinct redox states, but it is scarcely known whether sex differences in the functioning of these systems are involved. This study investigated, in an integrative view, sex differences in the nervous and immune systems of Swiss strain mice by analyzing behavior, immune function, and redox biomarkers across aging, to determine whether possible sex differences in homeostatic systems affect longevity. A longitudinal study was conducted on 20 female and male Swiss mice. At their young (2 mon), adult (7 mon), and old (18 mon) ages, subjects were subjected to a battery of behavioral tests, and peritoneal leukocytes were extracted to assess immune function and redox biomarkers. The natural deaths of animals were recorded for a longevity study. Our results indicate that sexual differences begin at a young age, and several are maintained until old age. Females, in general, show better behavior, immune function, and redox biomarkers, contributing to their higher longevity compared to males. The enhanced longevity in females may be attributable, in part, to the preservation of robust immune competence, with emphasis on innate immune functions and lower oxidative stress. The integration of behavioral and immunological profiles, together with redox biomarkers, underscores the critical importance of incorporating both sex as a biological variable in the design of aging-related research. Homeostatic systems (nervous, immune, and endocrine) are crucial for maintaining health throughout life and, consequently, relevant for the rate of aging and the longevity achieved. In many species, male and female mammals show different lifespans, attributed to distinct redox states, but it is scarcely known whether sex differences in the functioning of these systems are involved. This study investigated, in an integrative view, sex differences in the nervous and immune systems of Swiss strain mice by analyzing behavior, immune function, and redox biomarkers across aging, to determine whether possible sex differences in homeostatic systems affect longevity. A longitudinal study was conducted on 20 female and male Swiss mice. At their young (2 mon), adult (7 mon), and old (18 mon) ages, subjects were subjected to a battery of behavioral tests, and peritoneal leukocytes were extracted to assess immune function and redox biomarkers. The natural deaths of animals were recorded for a longevity study. Our results indicate that sexual differences begin at a young age, and several are maintained until old age. Females, in general, show better behavior, immune function, and redox biomarkers, contributing to their higher longevity compared to males. The enhanced longevity in females may be attributable, in part, to the preservation of robust immune competence, with emphasis on innate immune functions and lower oxidative stress. The integration of behavioral and immunological profiles, together with redox biomarkers, underscores the critical importance of incorporating both sex as a biological variable in the design of aging-related research. Homeostatic systems (nervous, immune, and endocrine) are crucial for maintaining health throughout life and, consequently, relevant for the rate of aging and the longevity achieved. In many species, male and female mammals show different lifespans, attributed to distinct redox states, but it is scarcely known whether sex differences in the functioning of these systems are involved. This study investigated, in an integrative view, sex differences in the nervous and immune systems of Swiss strain mice by analyzing behavior, immune function, and redox biomarkers across aging, to determine whether possible sex differences in homeostatic systems affect longevity. A longitudinal study was conducted on 20 female and male Swiss mice. At their young (2 mon), adult (7 mon), and old (18 mon) ages, subjects were subjected to a battery of behavioral tests, and peritoneal leukocytes were extracted to assess immune function and redox biomarkers. The natural deaths of animals were recorded for a longevity study. Our results indicate that sexual differences begin at a young age, and several are maintained until old age. Females, in general, show better behavior, immune function, and redox biomarkers, contributing to their higher longevity compared to males. The enhanced longevity in females may be attributable, in part, to the preservation of robust immune competence, with emphasis on innate immune functions and lower oxidative stress. The integration of behavioral and immunological profiles, together with redox biomarkers, underscores the critical importance of incorporating both sex as a biological variable in the design of aging-related research.Homeostatic systems (nervous, immune, and endocrine) are crucial for maintaining health throughout life and, consequently, relevant for the rate of aging and the longevity achieved. In many species, male and female mammals show different lifespans, attributed to distinct redox states, but it is scarcely known whether sex differences in the functioning of these systems are involved. This study investigated, in an integrative view, sex differences in the nervous and immune systems of Swiss strain mice by analyzing behavior, immune function, and redox biomarkers across aging, to determine whether possible sex differences in homeostatic systems affect longevity. A longitudinal study was conducted on 20 female and male Swiss mice. At their young (2 mon), adult (7 mon), and old (18 mon) ages, subjects were subjected to a battery of behavioral tests, and peritoneal leukocytes were extracted to assess immune function and redox biomarkers. The natural deaths of animals were recorded for a longevity study. Our results indicate that sexual differences begin at a young age, and several are maintained until old age. Females, in general, show better behavior, immune function, and redox biomarkers, contributing to their higher longevity compared to males. The enhanced longevity in females may be attributable, in part, to the preservation of robust immune competence, with emphasis on innate immune functions and lower oxidative stress. The integration of behavioral and immunological profiles, together with redox biomarkers, underscores the critical importance of incorporating both sex as a biological variable in the design of aging-related research.
ArticleNumber	204
Author	Garrido, Antonio Félix, Judith De la Fuente, Mónica
Author_xml	– sequence: 1 givenname: Judith orcidid: 0000-0003-3319-7623 surname: Félix fullname: Félix, Judith organization: Department of Genetics, Physiology and Microbiology. School of Biology, Complutense University of Madrid, Institute of Investigation Hospital 12 de Octubre (i+12), Hospital 12 de Octubre – sequence: 2 givenname: Antonio orcidid: 0000-0003-3026-3330 surname: Garrido fullname: Garrido, Antonio email: antonio.garrido@universidadeuropea.es organization: Institute of Investigation Hospital 12 de Octubre (i+12), Hospital 12 de Octubre, Nanocaging Research Group, Department of Biosciences, School of Biomedical Sciences and Health, Universidad Europea de Madrid – sequence: 3 givenname: Mónica orcidid: 0000-0002-5969-097X surname: De la Fuente fullname: De la Fuente, Mónica organization: Department of Genetics, Physiology and Microbiology. School of Biology, Complutense University of Madrid, Institute of Investigation Hospital 12 de Octubre (i+12), Hospital 12 de Octubre
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SubjectTerms	Age Age Factors Aging Aging - immunology Animals Anxiety Behavior Behavior, Animal - physiology Biological markers Biomarkers Biomarkers - metabolism Biomedical and Life Sciences Cell Biology Deaths Design of experiments Developmental Biology Estrogens Female Females Function Gender differences Geriatrics/Gerontology Hormones Immune response Immune system Immune System - physiology Immunity, Innate Laboratory animals Leukocytes Life expectancy Life Sciences Longevity Longevity - immunology Longevity - physiology Longitudinal studies Male Males Mental health Mice Motor ability Nutrition research Oxidation-Reduction Oxidative Stress Preservation Redox properties Research Article Research design Sex Characteristics Sex differences Sex Factors Sexes
Title	Sex differences in behavior, immune function, and redox state throughout life, and their effect on the longevity of Swiss mice
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