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Article: Time to Train: The Involvement of the Molecular Clock in Exercise Adaptation of Skeletal Muscle.

Mansingh, Shivani / Handschin, Christoph

2022 Volume 13, Page(s) 902031

Abstract: Circadian rhythms regulate a host of physiological processes in a time-dependent manner to maintain homeostasis in response to various environmental stimuli like day and night cycles, food intake, and physical activity. Disruptions in circadian rhythms ... ...

Abstract	Circadian rhythms regulate a host of physiological processes in a time-dependent manner to maintain homeostasis in response to various environmental stimuli like day and night cycles, food intake, and physical activity. Disruptions in circadian rhythms due to genetic mutations, shift work, exposure to artificial light sources, aberrant eating habits, and abnormal sleep cycles can have dire consequences for health. Importantly, exercise training efficiently ameliorates many of these adverse effects and the role of skeletal muscle in mediating the benefits of exercise is a topic of great interest. However, the molecular and physiological interactions between the clock, skeletal muscle function and exercise are poorly understood, and are most likely a combination of molecular clock components directly acting in muscle as well as in concordance with other peripheral metabolic organ systems like the liver. This review aims to consolidate existing experimental evidence on the involvement of molecular clock factors in exercise adaptation of skeletal muscle and to highlight the existing gaps in knowledge that need to be investigated to develop therapeutic avenues for diseases that are associated with these systems.
Language	English
Publishing date	2022-04-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2022.902031
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Article ; Online: Drugs, clocks and exercise in ageing: hype and hope, fact and fiction.

Furrer, Regula / Handschin, Christoph

The Journal of physiology

2022 Volume 601, Issue 11, Page(s) 2057–2068

Abstract: Ageing is a biological process that is linked to a functional decline, ultimately resulting in death. Large interindividual differences exist in terms of life- and healthspan, representing life expectancy and the number of years spent in the absence of ... ...

Abstract	Ageing is a biological process that is linked to a functional decline, ultimately resulting in death. Large interindividual differences exist in terms of life- and healthspan, representing life expectancy and the number of years spent in the absence of major diseases, respectively. The genetic and molecular mechanisms that are involved in the regulation of the ageing process, and those that render age the main risk factor for many diseases are still poorly understood. Nevertheless, a growing number of compounds have been put forward to affect this process. However, for scientists and laypeople alike, it is difficult to separate fact from fiction, and hype from hope. In this review, we discuss the currently pursued pharmacological anti-ageing approaches. These are compared to non-pharmacological interventions, some of which confer powerful effects on health and well-being, in particular an active lifestyle and exercise. Moreover, functional parameters and biological clocks as well as other molecular marks are compared in terms of predictive power of morbidity and mortality. Then, conceptual aspects and roadblocks in the development of anti-ageing drugs are outlined. Finally, an overview on current and future strategies to mitigate age-related pathologies and the extension of life- and healthspan is provided.
MeSH term(s)	Longevity/genetics ; Risk Factors
Language	English
Publishing date	2022-10-01
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP282887
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Article ; Online: Robust, Precise, and Deep Proteome Profiling Using a Small Mass Range and Narrow Window Data-Independent-Acquisition Scheme.

Fröhlich, Klemens / Furrer, Regula / Schori, Christian / Handschin, Christoph / Schmidt, Alexander

Journal of proteome research

2024 Volume 23, Issue 3, Page(s) 1028–1038

Abstract: In recent years, a plethora of different data-independent acquisition methods have been developed for proteomics to cover a wide range of requirements. Current deep proteome profiling methods rely on fractionations, elaborate chromatography, and mass ... ...

Abstract	In recent years, a plethora of different data-independent acquisition methods have been developed for proteomics to cover a wide range of requirements. Current deep proteome profiling methods rely on fractionations, elaborate chromatography, and mass spectrometry setups or display suboptimal quantitative precision. We set out to develop an easy-to-use one shot DIA method that achieves high quantitative precision and high proteome coverage. We achieve this by focusing on a small mass range of 430-670
MeSH term(s)	Animals ; Mice ; Proteome/analysis ; Software ; Mass Spectrometry/methods ; Proteomics/methods
Chemical Substances	Proteome
Language	English
Publishing date	2024-01-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2078618-9
ISSN	1535-3907 ; 1535-3893
ISSN (online)	1535-3907
ISSN	1535-3893
DOI	10.1021/acs.jproteome.3c00736
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Article ; Online: The molecular athlete: exercise physiology from mechanisms to medals.

Furrer, Regula / Hawley, John A / Handschin, Christoph

Physiological reviews

2023 Volume 103, Issue 3, Page(s) 1693–1787

Abstract: Human skeletal muscle demonstrates remarkable plasticity, adapting to numerous external stimuli including the habitual level of contractile loading. Accordingly, muscle function and exercise capacity encompass a broad spectrum, from inactive individuals ... ...

Abstract	Human skeletal muscle demonstrates remarkable plasticity, adapting to numerous external stimuli including the habitual level of contractile loading. Accordingly, muscle function and exercise capacity encompass a broad spectrum, from inactive individuals with low levels of endurance and strength to elite athletes who produce prodigious performances underpinned by pleiotropic training-induced muscular adaptations. Our current understanding of the signal integration, interpretation, and output coordination of the cellular and molecular mechanisms that govern muscle plasticity across this continuum is incomplete. As such, training methods and their application to elite athletes largely rely on a "trial-and-error" approach, with the experience and practices of successful coaches and athletes often providing the bases for "post hoc" scientific enquiry and research. This review provides a synopsis of the morphological and functional changes along with the molecular mechanisms underlying exercise adaptation to endurance- and resistance-based training. These traits are placed in the context of innate genetic and interindividual differences in exercise capacity and performance, with special consideration given to aging athletes. Collectively, we provide a comprehensive overview of skeletal muscle plasticity in response to different modes of exercise and how such adaptations translate from "molecules to medals."
MeSH term(s)	Humans ; Athletes ; Exercise/physiology ; Resistance Training ; Adaptation, Physiological ; Muscle, Skeletal ; Awards and Prizes ; Physical Endurance
Language	English
Publishing date	2023-01-05
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	209902-0
ISSN	1522-1210 ; 0031-9333
ISSN (online)	1522-1210
ISSN	0031-9333
DOI	10.1152/physrev.00017.2022
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Article ; Online: Effects of high-resistance wheel running on hallmarks of endurance and resistance training adaptations in mice.

Leuchtmann, Aurel B / Afifi, Yasmine / Ritz, Danilo / Handschin, Christoph

Physiological reports

2023 Volume 11, Issue 11, Page(s) e15701

Abstract: Exercise effectively promotes and preserves cardiorespiratory, neuromuscular, metabolic, and cognitive functions throughout life. The molecular mechanisms underlying the beneficial adaptations to exercise training are, however, still poorly understood. ... ...

Abstract	Exercise effectively promotes and preserves cardiorespiratory, neuromuscular, metabolic, and cognitive functions throughout life. The molecular mechanisms underlying the beneficial adaptations to exercise training are, however, still poorly understood. To improve the mechanistic study of specific exercise training adaptations, standardized, physiological, and well-characterized training interventions are required. Therefore, we performed a comprehensive interrogation of systemic changes and muscle-specific cellular and molecular adaptations to voluntary low-resistance wheel running (Run) and progressive high-resistance wheel running (RR) in young male mice. Following 10 weeks of training, both groups showed similar improvements in body composition and peak oxygen uptake (V̇O
MeSH term(s)	Humans ; Mice ; Male ; Animals ; Resistance Training ; Motor Activity/physiology ; Proteomics ; Physical Conditioning, Animal/physiology ; Adaptation, Physiological/physiology ; Muscle, Skeletal/metabolism ; Physical Endurance/physiology
Language	English
Publishing date	2023-06-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2724325-4
ISSN	2051-817X ; 2051-817X
ISSN (online)	2051-817X
ISSN	2051-817X
DOI	10.14814/phy2.15701
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Article ; Online: Caloric restriction and exercise "mimetics'': Ready for prime time?

Handschin, Christoph

Pharmacological research

2015 Volume 103, Page(s) 158–166

Abstract: Exercise and diet are powerful interventions to prevent and ameliorate various pathologies. The development of pharmacological agents that confer exercise- or caloric restriction-like phenotypic effects is thus an appealing therapeutic strategy in ... ...

Abstract	Exercise and diet are powerful interventions to prevent and ameliorate various pathologies. The development of pharmacological agents that confer exercise- or caloric restriction-like phenotypic effects is thus an appealing therapeutic strategy in diseases or even when used as life-style and longevity drugs. Such so-called exercise or caloric restriction "mimetics" have so far mostly been described in pre-clinical, experimental settings with limited translation into humans. Interestingly, many of these compounds activate related signaling pathways, most often postulated to act on the common downstream effector peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) in skeletal muscle. In this review, resveratrol and other exercise- and caloric restriction "mimetics" are discussed with a special focus on feasibility, chances and limitations of using such compounds in patients as well as in healthy individuals.
MeSH term(s)	Animals ; Caloric Restriction ; Drug Design ; Exercise ; Humans ; Physical Conditioning, Animal
Language	English
Publishing date	2015-12-02
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2015.11.009
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Article ; Online: Lifestyle vs. pharmacological interventions for healthy aging.

Furrer, Regula / Handschin, Christoph

Aging

2020 Volume 12, Issue 1, Page(s) 5–7

MeSH term(s)	Animals ; Early Medical Intervention/methods ; Healthy Aging ; Humans ; Life Style
Language	English
Publishing date	2020-01-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.102741
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Article ; Online: Pharmacological targeting of age-related changes in skeletal muscle tissue.

Leuchtmann, Aurel B / Handschin, Christoph

Pharmacological research

2019 Volume 154, Page(s) 104191

Abstract: Sarcopenia, the age-related loss of skeletal muscle mass and function, increases the risk of developing chronic diseases in older individuals and is a strong predictor of disability and death. Because of the ongoing demographic transition, age-related ... ...

Abstract	Sarcopenia, the age-related loss of skeletal muscle mass and function, increases the risk of developing chronic diseases in older individuals and is a strong predictor of disability and death. Because of the ongoing demographic transition, age-related muscle weakness is responsible for an alarming and increasing contribution to health care costs in Western countries. Exercise-based interventions are most successful in preventing the decline in skeletal muscle mass and in preserving or ameliorating functional capacities with increasing age. However, other treatment options are still scarce. In this review, we explore currently applied nutritional and pharmacological approaches to mitigate age-related muscle wasting, and discuss potential future therapeutic avenues.
MeSH term(s)	Aging ; Animals ; Humans ; Muscle, Skeletal ; Sarcopenia/drug therapy
Language	English
Publishing date	2019-03-04
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2019.02.030
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Article ; Online: In-vivo assessment of retinal vessel diameters and observer variability in mice: A methodological approach.

Streese, Lukas / Liffert, Jeannine / Vilser, Walthard / Handschin, Christoph / Hanssen, Henner

PloS one

2022 Volume 17, Issue 7, Page(s) e0271815

Abstract: Background: Central retinal arteriolar (CRAE) and venular (CRVE) diameter equivalents are predictive for cardiovascular and all-cause mortality in humans. The aim of this study was to investigate the inter- and intraobserver variability for the ... ...

Abstract	Background: Central retinal arteriolar (CRAE) and venular (CRVE) diameter equivalents are predictive for cardiovascular and all-cause mortality in humans. The aim of this study was to investigate the inter- and intraobserver variability for the assessment of CRAE and CRVE in mice using fluorescein contrast enhancement as compared to crude analysis. Methods: Three high quality images with (F) and without fluorescein (NF) of eight mice (type C57BL) were recorded and analysed by two independent experienced investigators to investigate interobserver variability. In addition, one investigator analysed 20 F and 20 NF images twice to investigate intraobserver variability. The time course of CRAE and CRVE vessel responses after fluorescein injection were recorded in one mouse every 30 seconds for 15 minutes. Results: The interobserver variability was lower in F images compared to NF images for CRAE (r = 0.99, p < 0.001 vs. r = 0.65, p = 0.083) and CRVE (r = 0.99, p < 0.001 vs. r = 0.79, p = 0.019). Intraobserver variability for CRAE (r = 0.99, p < 0.001 vs. r = 0.48, p = 0.032) and CRVE (r = 0.98, p < 0.001 vs. r = 0.86, p < 0.001) were lower in F compared to NF images. Fluorescein injection induced vascular staining mimicking vessel dilation (+14%) followed by a long-lasting stable staining phase well suited for precise measurements. Conclusions: Measurement variability can be optimized by use of fluorescein as contrast enhancement in mice. Standardization for time of image acquisition after fluorescein injection is advisable. Translation of static retinal vessel analysis into a rodent model has the potential to bridge the research gap between proof of concept studies in animals and clinical studies in humans.
MeSH term(s)	Animals ; Arterioles ; Fluoresceins ; Humans ; Mice ; Mice, Inbred C57BL ; Retinal Vessels/diagnostic imaging ; Venules
Chemical Substances	Fluoresceins
Language	English
Publishing date	2022-07-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0271815
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Article ; Online: How Epigenetic Modifications Drive the Expression and Mediate the Action of PGC-1α in the Regulation of Metabolism.

Krämer, Anne I / Handschin, Christoph

International journal of molecular sciences

2019 Volume 20, Issue 21

Abstract: Epigenetic changes are a hallmark of short- and long-term transcriptional regulation, and hence instrumental in the control of cellular identity and plasticity. Epigenetic mechanisms leading to changes in chromatin structure, accessibility for ... ...

Abstract	Epigenetic changes are a hallmark of short- and long-term transcriptional regulation, and hence instrumental in the control of cellular identity and plasticity. Epigenetic mechanisms leading to changes in chromatin structure, accessibility for recruitment of transcriptional complexes, and interaction of enhancers and promoters all contribute to acute and chronic adaptations of cells, tissues and organs to internal and external perturbations. Similarly, the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is activated by stimuli that alter the cellular energetic demand, and subsequently controls complex transcriptional networks responsible for cellular plasticity. It thus is of no surprise that PGC-1α is under the control of epigenetic mechanisms, and constitutes a mediator of epigenetic changes in various tissues and contexts. In this review, we summarize the current knowledge of the link between epigenetics and PGC-1α in health and disease.
MeSH term(s)	Adipose Tissue, Brown/metabolism ; Animals ; DNA Methylation ; Energy Metabolism/genetics ; Epigenesis, Genetic ; Gene Expression Regulation ; Humans ; Obesity/genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics
Chemical Substances	PPARGC1A protein, human ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Language	English
Publishing date	2019-10-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms20215449
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