Urine biomarkers detect sarcopenia
Sarcopenia has a big impact on health as we age – and it’s not just about the risk of falls. It is estimated to affect 10–16% of the aging population but challenges with diagnosis mean that this is likely to be an underestimate. Current methods of analysing muscle all have limitations associated with them. CLI chatted with Dr Rafaela Andrade (Myomar Molecular Inc, Canada) and Professor John Frampton (Dalhousie University, Canada) to find out more about the panel of biomarkers that they have selected to create a urine test for early detection of sarcopenia rand how this can be beneficial for mitigating or reversing sarcopenia.
What is sarcopenia and what is the importance of recognizing it?
Sarcopenia is a disease that is becoming much more recognized as very important for longevity and for overall health into older age, which is why we were keen to study it. In scientific terms, sarcopenia is the progressive loss of muscle mass and muscle function over time, and, when that happens, it affects different types of organs in our body. For example, skeletal muscle is very important for bone protection, for our cardiovascular health, for cognitive function of the brain. Because muscle loss has a huge impact on these different organs and is linked to many different diseases, it is now known that it is very important to recognize and diagnose sarcopenia. Another reason to diagnose sarcopenia is that it can be prevented and people don’t necessarily have to lose muscle health with age. However, this takes some work but it’s very worthwhile as preventing or reversing sarcopenia improves the prognosis of many diseases. For example, if you have stronger muscles there is a better outcome from surgery and even cancer treatments.
How is sarcopenia normally diagnosed?
Today, there are a couple of different techniques to diagnose sarcopenia, but none of them are specific enough to be recognized as the gold standard diagnostic tool.
Imaging
We do have techniques that use imaging, for example, dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI). DXA scanning was first used for bone density, but there is a measure-ment called appendicular lean muscle index that can be used as a sarcopenia index that we can use that to determine how much muscle mass individuals are losing over time. If the results fall below a certain threshold, sarcopenia is diagnosed.
Physical assessment
Functional tests are also currently used to assess muscle health, these include the Short physical performance battery (SPPB), which is a panel of physical assessments that physicians use to understand overall muscle function, and grip strength. The SPPB is a standardized tool is mainly used in primary healthcare settings and aims to provide an objective and reproducible assessment of lower extremity function.
Serum markers
The ratio of creatinine to cystatin C in serum is also used to predict overall muscle mass.
Urine test
Additionally, there is a urine test as well. This uses an oral tracer dose of D3 creatine which is processed by the body, and the enrichment of D3-creatinine is measured in the urine via liquid chromatography-tandem mass spectrometry (LC-MS/MS). This provides a total body muscle mass estimate that correlates strongly with MRI results.
Exercise and nutrition advice can help to prevent and reverse sarcopenia
(Shutterstock.com)
What are the limitations of these methods?
Detection of muscle mass rather than muscle quality
Firstly, most of the techniques provide information on overall muscle mass, which is then used to predict muscle quality. This is a limitation because they provide minimal information about the actual muscle quality, which is known to be one of the most important things for skeletal muscle health. Muscle mass is not always related to muscle quality; for example, with body builders, we know that they have a lot of muscle mass, but when we look at the muscle quality, it’s not always there.
Late detection of sarcopenia
Secondly, most of these techniques only really provide a good prediction of sarcopenia when a lot of muscle loss has already occurred. These methods are not very good at diagnosing early stage changes to muscle, and they cannot be very precise when
a person is very close to the sarcopenia cut-off level. So although most of the techniques are ideal at identifying when muscle mass has been lost, they are missing the early stages of detection.
Lack of accessibility
Another limitation of most of the current tests is that they lack accessibility. There is only very limited access for most people to MRI or DXA scanning. For the current urine test, not everyone will have the time to take the tracer isotope and wait for that to be metabolized and to appear in the urine. For the serum test, that also requires a trip to location where a blood specimen can be taken.
Subjective assessment/patient capability
Although the SPPB was designed to be an objective process from the point of view of the assessor, subjectiveness and variability can be a problem because it depends on the willingness of the patients to do it. Also, in some situations, such as when the patient is bed-bound or has cognitive limitations, it is not possible to perform these tests accurately.
How can diagnosis be improved?
Given the limitations described above of the current tests, we wanted to develop a method that could be used to detect muscle loss in its early stages and that could be used as more of an action plan, not just a cut-off to say, “Yes, you have sarcopenia”, or “No, you don’t have sarcopenia”. We decided to search the field to identify specific biomarkers that had an implication in overall muscle health and muscle quality. We wanted to look into specific metabolites before someone had sarcopenia, and when they start having sarcopenia, what happened with these biomarkers? We wanted to be able to monitor biomarkers over time to see how they change with aging, with different disorders and with medications that affect muscle, and to able to visualize a gradient of a patient’s levels of muscle loss over time.
To do this, we compared different populations, sedentary individuals to more active individuals, and we looked into the biomarker profile of these two populations. Then we discovered a list of biomarkers that displayed a significant difference between these populations. Then we gave the specific populations a DXA scan and physical assessment and used those two standards to determine if they have sarcopenia or not. We were then able to select a specific panel of biomarkers that correlated with the diagnosis of sarcopenia by DXA scan and also by physical assessment. The five biomarkers that we selected for the panel are L-glutamic acid, xanthine, taurine, succinate and L-carnitine. They have different functions in the body but are all important for muscle metabolism and corresponded to the diagnosis of sarcopenia by DXA scan and physical assessment. Even better, the biomarkers used for the panel were detectable in urine.
Advantages of our test
The advantages of the test that we have developed, therefore, are that it uses urine as a specimen (so it’s non-invasive and readily accessible to everyone), it’s inexpensive and fast to do (because there are only five biomarkers that are accessible to detect via existing assays), identifies early changes associated with sarcopenia, and reflects better muscle quality than quantity.
Personalized plans for mitigating or reversing sarcopenia
Now, because we have developed a scoring system corresponding to the gradient of these biomarkers that shows your risk of sarcopenia and because we know the specific level of each of the biomarkers (which all have important roles in muscle growth or degradation), we can provide a precision-medicine approach for people to improve their overall muscle health by creating individually tailored action plans.
Most of the recommendations will be around nutrition and exercise.
However, it’s not all about doing or eating ‘more’. If the biomarker levels are elevated, we also see that as a negative too, not just if levels are low. We really want to establish what it is optimal for the person. And then looking into the levels of the individual markers on the panel, we can then predict what best foods that person should be eating, types of supplements that would be good to take, as well as exercise frequency and intensity too. Intensity of exercise is important too, because we see some levels of muscle degradation if people exercise too hard or too much, or they are overtraining. For example, with athletes or weekend warriors who exercise at a higher frequency, overtraining can result in oxidative stress levels and degradation of muscle fibres. So we are working on recommendations regarding diet (and supple-mentation if necessary) as well as exercise frequency and intensity tailored to the individual.
As we mentioned earlier, medication can have an effect on muscle health. For example, many people in older age are prescribed statins to reduce low-density lipoproteins in the blood and so to reduce the risk of serious cardiovascular conditions or events. However, for some people, statins affect skeletal muscle health – so in addition to monitoring cardiovascular health, it is also important to monitor skeletal muscle health. We have conducted case studies to look at the impact of statins on skeletal muscle health by testing people every three months who were taking statins. In some cases, when people lose a lot of muscle quality immediately, we gave specific recommendations to decrease these effects on skeletal muscle health, and we saw quite a bit of improvement in some of them.
Another, increasingly large, group of people at risk of reduced muscle health are those taking GLP-1 medications, so we would recommend that this population also checks their muscle health often.
We are able to give people more knowledge of how therapeutics can affect skeletal muscle health with the goal to change the trajectory of developing sarcopenia and even preventing it as you continue to age.
What are your thoughts on future perspectives of this field?
The next step for us is to make this test as accessible as possible. We want to give people the ability to detect the biomarkers at home using something similar to a pregnancy test, so people can actually see the status of their muscle health at home and then give them the specific guidance to improve it. In that way, we can protect overall muscle quality over time – we give people better quality of life just by looking at muscle because, really, muscle is our longevity organ. There are many health benefits that arise from simply having a good overall skeletal muscle system. Another task is to make our scoring system as accessible as possible, and we are working on both of these things right now.
In addition to this first publication, we developed a company based on this technology – Myomar Molecular Inc (https://www.myomarmolecular.ca/), and we now have a product available on the market in Canada and the USA. We are working on more research on this specific panel of biomarkers, within different topics (such as the pelvic floor, and menopausal women), and we will publish our findings. We have a lot of interest in research and developing a product that it is an accessible way of assessing skeletal muscle health as people continue aging or overcome diseases.
Urine is an easy specimen to collect for biomarker anaysis (Shutterstock.com)
How can diagnosis be improved?
Given the limitations described above of the current tests, we wanted to develop a method that could be used to detect muscle loss in its early stages and that could be used as more of an action plan, not just a cut-off to say, “Yes, you have sarcopenia”, or “No, you don’t have sarcopenia”. We decided to search the field to identify specific biomarkers that had an implication in overall muscle health and muscle quality. We wanted to look into specific metabolites before someone had sarcopenia, and when they start having sarcopenia, what happened with these biomarkers? We wanted to be able to monitor biomarkers over time to see how they change with aging, with different disorders and with medications that affect muscle, and to able to visualize a gradient of a patient’s levels of muscle loss over time.
To do this, we compared different populations, sedentary individuals to more active individuals, and we looked into the biomarker profile of these two populations. Then we discovered a list of biomarkers that displayed a significant difference between these populations. Then we gave the specific populations a DXA scan and physical assessment and used those two standards to determine if they have sarcopenia or not. We were then able to select a specific panel of biomarkers that correlated with the diagnosis of sarcopenia by DXA scan and also by physical assessment. The five biomarkers that we selected for the panel are L-glutamic acid, xanthine, taurine, succinate and L-carnitine. They have different functions in the body but are all important for muscle metabolism and corresponded to the diagnosis of sarcopenia by DXA scan and physical assessment. Even better, the biomarkers used for the panel were detectable in urine.
Advantages of our test
The advantages of the test that we have developed, therefore, are that it uses urine as a specimen (so it’s non-invasive and readily accessible to everyone), it’s inexpensive and fast to do (because there are only five biomarkers that are accessible to detect via existing assays), identifies early changes associated with sarcopenia, and reflects better muscle quality than quantity.
Personalized plans for mitigating or reversing sarcopenia
Now, because we have developed a scoring system corresponding to the gradient of these biomarkers that shows your risk of sarcopenia and because we know the specific level of each of the biomarkers (which all have important roles in muscle growth or degradation), we can provide a precision-medicine approach for people to improve their overall muscle health by creating individually tailored action plans.
Most of the recommendations will be around nutrition and exercise.
However, it’s not all about doing or eating ‘more’. If the biomarker levels are elevated, we also see that as a negative too, not just if levels are low. We really want to establish what it is optimal for the person. And then looking into the levels of the individual markers on the panel, we can then predict what best foods that person should be eating, types of supplements that would be good to take, as well as exercise frequency and intensity too. Intensity of exercise is important too, because we see some levels of muscle degradation if people exercise too hard or too much, or they are overtraining. For example, with athletes or weekend warriors who exercise at a higher frequency, overtraining can result in oxidative stress levels and degradation of muscle fibres. So we are working on recommendations regarding diet (and supple-mentation if necessary) as well as exercise frequency and intensity tailored to the individual.
As we mentioned earlier, medication can have an effect on muscle health. For example, many people in older age are prescribed statins to reduce low-density lipoproteins in the blood and so to reduce the risk of serious cardiovascular conditions or events. However, for some people, statins affect skeletal muscle health – so in addition to monitoring cardiovascular health, it is also important to monitor skeletal muscle health. We have conducted case studies to look at the impact of statins on skeletal muscle health by testing people every three months who were taking statins. In some cases, when people lose a lot of muscle quality immediately, we gave specific recommendations to decrease these effects on skeletal muscle health, and we saw quite a bit of improvement in some of them.
Another, increasingly large, group of people at risk of reduced muscle health are those taking GLP-1 medications, so we would recommend that this population also checks their muscle health often.
We are able to give people more knowledge of how therapeutics can affect skeletal muscle health with the goal to change the trajectory of developing sarcopenia and even preventing it as you continue to age.
What are your thoughts on future perspectives of this field?
The next step for us is to make this test as accessible as possible. We want to give people the ability to detect the biomarkers at home using something similar to a pregnancy test, so people can actually see the status of their muscle health at home and then give them the specific guidance to improve it. In that way, we can protect overall muscle quality over time – we give people better quality of life just by looking at muscle because, really, muscle is our longevity organ. There are many health benefits that arise from simply having a good overall skeletal muscle system. Another task is to make our scoring system as accessible as possible, and we are working on both of these things right now.
In addition to this first publication, we developed a company based on this technology – Myomar Molecular Inc (https://www.myomarmolecular.ca/), and we now have a product available on the market in Canada and the USA. We are working on more research on this specific panel of biomarkers, within different topics (such as the pelvic floor, and menopausal women), and we will publish our findings. We have a lot of interest in research and developing a product that it is an accessible way of assessing skeletal muscle health as people continue aging or overcome diseases.
Bibliography
1. Beaudart C, McCloskey E, Bruyère O, Cesari M, Rolland Y et al. Sarcopenia in daily practice: assessment and management. BMC Geriatr. 2016;16(1):170. PMID: 27716195 (https://doi.org/10.1186/s12877-016-0349-4).
2. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O et al. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 2019;48(1):16–31. PMID: 3031237 (https://doi.org/10.1093/ageing/afy169).
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4. Sánchez-Sánchez JL, He L, Morales JS, de Souto Barreto P, Jiménez-Pavón D et al. Association of physical behaviours with sarcopenia in older adults: a systematic review and meta-analysis of observational studies. Lancet Healthy Longev. 2024;5(2):e108–e119. PMID: 38310891 (https://doi.org/10.1016/s2666-7568(23)00241-6).
5. Zhang H, Qi G, Wang K, Yang J, Shen Y et al. Oxidative stress: roles in skeletal muscle atrophy. Biochem. Pharmacol. 2023;214:115664. PMID: 37331636 (https://doi.org/10.1016/j.bcp.2023.115664).
The interviewees
Dr Rafaela Andrade PhD,
Co-founder and CEO of Myomar Molecular
Myomar Molecular Inc, Sudbury, ON, Canada
Email address: rpandrade@myomarmolecular.com
Professor John Frampton PhD,
School of Biomedical Engineering, Department of Biochemistry and Molecular Biology (Cross Appointment), Dalhousie University, Faculties of Medicine and Engineering, Halifax, NS, Canada
Email address: john.frampton@dal.ca
For further information, see:
“Metabolite Biomarkers Present in Urine Predict Alterations in Skeletal Muscle Associated with Sarcopenia” by Andrade-Vieira R, Feridooni HA, Teixeira A, Deska-Gauthier D, Chang X, Karakach T, Moyer R, Frampton JP. Front Aging. 2026;7:1736916. PMID: 41939145 (https://shorturl.at/n7Zrx).