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Exercise-induced muscle exosomes & human aging Undergraduate and graduate research opportunities in exercise science, cell biology, molecular biology, immunology, and molecular therapeutics

Dr. Jennifer Klein (UWL, Biology); jklein@uwlax.edu

Dr. Daniel Freidenreich (UWL, ESS); dfreidenreich@uwlax.edu

None of us will escape aging (and death), so scientists have shifted their focus to the more reasonable goal of lengthening human healthspan, the number of years lived without the burden of age-related disease or degeneration. Decades of scientific exploration have led back to an intervention that we intuitively knew was a key to healthy aging—exercise.

Exercise exerts powerful anti-aging effects that impact every aspect of physiology and function, particularly mood, cognition, cardiovascular health, musculoskeletal strength, and immune system regulation. Of course, not everyone can exercise; injuries, disease, mental illness, and aging can strongly limit participation. And unfortunately, older individuals do not respond to exercise with the robust regeneration and renewal observed for young people.

We seek therapies that mimic or boost the effects of exercise to boost the health of older people and to support the rehabilitation of patients who cannot exercise.

One of the most exciting developments in biomedical science is the discovery of exosomes, which are lipid-encapsulated packets of DNA, RNA, and proteins that can be detected in blood, urine, etc. (see photo on left). Exosomes are released from all tissues, particularly exercising muscle. They travel through the bloodstream, potentially communicating a yet undeciphered message to the entire body.

There is some evidence that the messages contained within exosomes are encoded in regulatory RNAs, which unlike DNA, play a role far beyond storing genetic information. MicroRNAs (miRNAs) are short (20 nucleotides) messages that enter target cells and inhibit the production of particular proteins, potentially altering cell function and overall physiology. Every exosome can contain thousands of unique miRNAs, each with a distinct molecular target. Muscle exosomes and the miRNAs they contain could be the mysterious messengers that mediate the whole-body, anti-aging effects of exercise.

Aim 1. Determine the impact of exercise-induced exosomes collected from young and old human subjects before and after intense resistance training on in vitro (cultured cells) model systems of muscle regeneration and immune cell regulation.

The proposed work blends expertise from the fields of exercise science (Dr. Daniel Freidenreich UWL ESS) and molecular cell biology (Dr. Jennifer Klein, UWL Biology) to produce molecular-level insights into the effects of exosomes from humans who are varied in their age and biological sex and undergoing impactful activities such as exercise on muscle regeneration and immune cell regulation.

We use mammalian cell culture techniques to grow and differentiate muscle stem cells, muscle myotubes, and macrophages. Some of the tools we use for understanding their function include fluorescence microscopy and quantitative PCR to measure gene expression.

Aim 2. Characterize the full profile of miRNAs contained within exercise-induced exosomes from young and old subjects. We have entered a new era of biology in which it is technically and financially feasible to sequence every DNA and RNA contained within a cell, fluid, or exosome. Although valuable information in and of itself, we will ultimately take advantage of these miRNA profiles in combination with the biological impacts measured in Aim 1 to identify a handful of candidates for novel RNA therapeutics.

RNA sequencing of exosomes isolated from human subjects undergoing resistance training exercises

Undergraduate research assistant, Emily Mauch, prepping exosomes

We are currently recruiting undergraduates and graduate students on projects in cell biology, microscopy, molecular biology, and immunology.

For information on research opportunties, contact Dr. Jennifer Klein: jklein@uwlax.edu; Prairie Springs Science Center 4040

Dr. Klein, Dr. Freidenreich, and student researchers, including Cade Armstrong, carrying out an experiment
Created By
Jennifer Klein
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Credits:

Research photos by Michael Lieurance (University of Wisconsin-La Crosse) Created with an image by LIGHTFIELD STUDIOS - "Close-up partial view of sportswoman lifting barbell at gym workout"