The African killifish: A short-lived vertebrate model to study the biology of sarcopenia and longevity
Details
Publication Year 2024-01,Volume 23,Issue #1,Page e13862
Journal Title
Aging Cell
Publication Type
Research article
Abstract
Sarcopenia, the age-related decline in muscle function, places a considerable burden on health-care systems. While the stereotypic hallmarks of sarcopenia are well characterized, their contribution to muscle wasting remains elusive, which is partly due to the limited availability of animal models. Here, we have performed cellular and molecular characterization of skeletal muscle from the African killifish-an extremely short-lived vertebrate-revealing that while many characteristics deteriorate with increasing age, supporting the use of killifish as a model for sarcopenia research, some features surprisingly reverse to an "early-life" state in the extremely old stages. This suggests that in extremely old animals, there may be mechanisms that prevent further deterioration of skeletal muscle, contributing to an extension of life span. In line with this, we report a reduction in mortality rates in extremely old killifish. To identify mechanisms for this phenomenon, we used a systems metabolomics approach, which revealed that during aging there is a striking depletion of triglycerides, mimicking a state of calorie restriction. This results in the activation of mitohormesis, increasing Sirt1 levels, which improves lipid metabolism and maintains nutrient homeostasis in extremely old animals. Pharmacological induction of Sirt1 in aged animals was sufficient to induce a late life-like metabolic profile, supporting its role in life span extension in vertebrate populations that are naturally long-lived. Collectively, our results demonstrate that killifish are not only a novel model to study the biological processes that govern sarcopenia, but they also provide a unique vertebrate system to dissect the regulation of longevity.
Publisher
Wiley
Keywords
Animals; *Longevity; *Sarcopenia/metabolism; Sirtuin 1/metabolism; Aging; Muscle, Skeletal/metabolism; Fundulus heteroclitus; Vertebrates; Biology; killifish; longevity; mitohormesis; sarcopenia; skeletal muscle
Department(s)
Laboratory Research
Open Access at Publisher's Site
https://doi.org/10.1111/acel.13862
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2024-02-20 07:04:49
Last Modified: 2024-02-20 07:05:27

© 2024 The Walter and Eliza Hall Institute of Medical Research. Access to this website is subject to our Privacy Policy and Terms of Use

An error has occurred. This application may no longer respond until reloaded. Reload 🗙