Counteracting Age-Related Loss of Skeletal Muscle Mass (CALM)

Growing number of elderly

In the coming decades, the number of elderly citizens over age 60 in Denmark will increase by more than 50%. As a consequence, public expenditures for health care and welfare services will rapidly increase unless new evidence-based measures are developed to counteract age-related challenges.

One of the most significant challenges is the age-related loss of skeletal muscle mass (1-2% per year), which starts around age 50 in healthy individuals. Thus, with a larger elderly population, society will face significant challenges; how to maintain the elderly’s independence and quality of life, and how to avoid unwanted changes in their everyday practices due to skeletal muscle loss.

Combating muscle loss

It is widely recognised that physical-activity levels decrease with ageing and daily food intake also declines, especially protein intake. With regard to these factors, it is believed that age-dependent muscle loss can be partially diminished with an increased intake of dietary protein, and is optimally counteracted when adequate protein intake is combined with resistance training.

However, this raises several questions about the usefulness of the present knowledge, especially with regard to protein intake and exercise as strategies and general recommendations for the elderly to combat muscle loss.

Focusing on long-term benefits of exercise

While the benefit from an intensive, training centre-based, heavy-resistance exercise program is hypothesised to be superior to other interventions as long as supervision and individual control are performed, long-term adherence to such a program must be questioned.

Conversely, greater adherence to more moderately-intensive, home-based training programs is expected and thus the long-term benefit exceeds that of the heavy-resistance exercise strategy.

The effect of increased protein intake on gut microbiota 

It is known that the complexity in the composition of human gut microbiota decreases with age, but how these changes correlate with metabolome changes is not known. Further, the effect of increased protein intake on gut microbiota composition and blood metabolome among the elderly is not known, but it is likely to have a strong effect on both.

Everyday-life practices

We aim to investigate these questions by addressing not only the physiological response of the human body to different combinations of protein and exercise, but also by exploring everyday-life practices and societal structures that may support or hinder the successful implementation of changes in elderly people’s daily lives.

CALM vision

The overall vision of this project is to formulate evidence-based strategies and recommendations, which will be appropriate to the everyday practices of the elderly population.

CALM multidisciplinarity

Our claim is that, in order to develop such recommendations, it is necessary to take a multidisciplinary approach. Thus, we have designed a highly innovative research project that integrates studies of molecular, physiological and microbiological characteristics and adaptations together with historical, sensory and ethnographic investigations of lifestyle behaviour.

• Protein intake and levels of exercise:
  • skeletal muscle mass and function
  • gut microbiota and metabolome
• Lifestyle changes in everyday practices
• Socio-cultural and historical paradigms of ageing
• Consumer studies and development of food prototypes
• Stakeholder involvement

The CALM project consists of two interdependent project clusters:

The first cluster is a clinical intervention study conducted at the individual level; it will have an integrated design that combines physiological and cultural perspectives and approaches. The aim is to obtain evidence from the interventions on physiological and functional parameters as well as to explore individual and social conditions that may prevent the elderly from making lifestyle changes.

The second cluster is a design-driven intervention targeted at the societal level; it includes historical and stakeholder analyses as well as an innovation project. The aim of Cluster 2 is to identify and create platforms for public dialogue, and to develop new recommendations (lifestyle and exercise regimens) and products (services and foods).

The clinical trials

Age-dependent loss of skeletal muscle mass is a well-described phenomenon starting at the age of around 50-60 years. Over time the loss of muscle mass will compromise the physical capabilities and for some citizens it will result in drastic changes in life and make the elderly individual dependent on help to accomplish activities of daily living.

Therefore, with the purpose to formulate useful and feasible recommendations for public institutions as well as individual citizens, strategies to diminish the weakening of muscle mass are necessary. A number of factors that stimulate the growth of skeletal muscle are known.

Especially daily intake of protein and physical activities are important for maintaining muscle mass and functional ability. We know that food rich in protein combined with heavy resistance training result in the largest muscle growth.

But the relationship between protein intake and training and its type/intensity is unknown – but it could be hypothesized that light intensity training performed in people’s own homes can be an advantage, and will get more elderly people to comply with the training modality.

In this project we will therefore investigate different training strategies and daily protein supplementation in elderly people in a 1-year intervention trial. We will evaluate on various factors such as muscle size, strength, structure and function, gut microbiota, and conduct interviews on selected participants to describe the impact of the interventions on the elderly’s life.

Method

All voluntary participants are randomly stratified into one of five groups. All groups must be supplied twice daily for a year! Four groups have to supplement with 2 x 20 g protein and the fifth group, which make up a placebo-control group, supplement themselves with 2 x 20 g carbohydrate. The groups are as follows:

• Heavy and center-based resistance training and milk protein: two to three training sessions per week and two times 20 g protein beverage daily.
• Light load and home-based resistance training and milk protein: three to five training sessions per week and two times 20 g protein beverage daily.
• Milk protein: continue their normal daily life and supplement daily with two times 20 g whey protein.
• Control-protein: continue their normal daily life and supplement daily with two times 20 g collagen-based protein.
• Placebo-protein: continue their normal daily life and supplement daily with two times 20 g carbohydrate.

From each intervention group, a number of subjects are randomly assigned to participate in a sub-group in which we investigate the anabolic potential to protein intake before and after the intervention. In addition, participants from each group are selected for a qualitative study of food and physical activity in daily life. These investigations are carried out as a combination of observations and interviews.

Purpose

The overall purpose of this project is to create evidence for the formulation of effective and feasible strategies to maintain muscle mass and function in the healthy ageing population.

Hypotheses

1. The adaptation of muscle size, muscle structure and muscle function in elderly healthy people is improved by intake of protein and is enhanced when combined with light load training intensity and more with heavy load resistance exercise.
2. One year resistance training reduces the abundance of sucker-cross-links in connective tissue and improves the stiffness of the tissue.
3. Increased intake of protein does improve the gut microbiota evenly as when combined with resistance exercise.
4. Intake of nutrient supplementation over a one year course affects the subjects’ acceptance of the supplement. This change is dependent on the otherwise impact of the intervention on the subjects’ general health.
5. The subjects represent various life styles that can be affected differently by the same interventions.

Start and location

The intervention was started in early 2014 and is carried out at Institute of Sports Medicine, Copenhagen (www.ISMC.dk), Bispebjerg Hospital.

Historical analysis

The historical analysis will focus on socio-cultural and historical paradigms and practices regarding the importance of food and exercise to elderly citizen’s health and quality of life. The analyses will be conducted to support the adaptability of the innovative strategies by ensuring that they are attuned to the societal and cultural realities of the elderly.

Historical analyses of the life of the elderly have hitherto been scant, mainly focusing on the development of laws and public and private institutions, or on the diagnosis of "old age". The historical study will focus on: 

previous experiences from clinical research and practices related to the prevention of age-related loss of muscle mass through exercise and diet; 
the scientific and societal paradigms of health in old age, with a specific focus on dietary and physical-activity recommendations over the past 50 years. Furthermore, we will analyse how these current understandings of health in old age have shaped public and private initiatives; and 
a historical investigation of eldercare practices in the municipality of Copenhagen.
In addition to gathering knowledge about previous public experiences with diet and activity, the historical analysis will provide novel insights into the development of the welfare state, its eldercare institutions and its increasing focus on health and health promotion in old age.

The analyses will rely on textbooks about gerontology, geriatrics, human nutrition and physiology as well as relevant scientific research projects published or widely used in Denmark between 1960 and 2012. Municipal regulations from Copenhagen, archives from nursing homes and home care in Copenhagen from 1960–2012, as well as interviews with healthcare professionals, will also be included.

Everyday-life study

The possibilities for and hindrances to lifestyle changes
Adherence to health recommendations that involve making changes to daily life and routines is a major personal and societal challenge. It is well-known that there are many barriers within individuals’ behaviour and everyday-life practices that may prevent adoption of a healthier lifestyle. There is very little known about how to make changes and maintain a healthy life-style.

This study suggests that a thorough investigation of the everyday-life practices of the elderly involved in the clinical trial – specifically, how they adapt to the clinical intervention, and how it affects their routines and habits – will provide valuable knowledge about how lifestyle changes can be prompted.

In order to examine the impact – both positive and negative – of the clinical trial on everyday practices, a sample of the research population (ten from each group) will be selected and followed during the one-year trial and its follow-up studies.

Specifically, the individuals’ adherence to consuming extra protein and performing home-based low-intensity training or supervised heavy-resistance training will be compared in order to gain knowledge about the barriers and possibilities for lifestyle change among the target population.

Tests, observations, and interviews
The methodology employed will be qualitative, involving participant observation at the clinic and in the participants’ homes as well as in-depth interviews, visual methods and auto-ethnography. In addition, quantitative tests of the sensory hedonic response to applied protein supplementation and its appropriateness in different usages will be conducted during the intervention period.

This will produce knowledge about the effects of increased protein intake and different exercise regimens on health-related behaviour and quality of life, providing insights into the elderly’s;

• independence
• social relations and networks
• eating practices
• fatigue
• vitality
• physical and social well-being

Furthermore, life-story interviews will be conducted to obtain knowledge about how routines and habits have become established in the participants’ everyday lives, and how lifestyle changes earlier in life were experienced.

Product development and consumer evaluation

The CALM project consists of an intervention phase and an innovation phase where sensory and consumer research is involved in both phases.

In the intervention phase, the focus is on how the sensory acceptance of the dietary supplement develops over time as an effect of the daily repeated exposure among the CALM cohort participants. The one-year intervention and follow up period provides a unique opportunity to study the development of sensory acceptance of an initially unfamiliar product such as dietary supplements.

It is expected that there will be some who experience a positive change in well-being due to the intervention among the experimental groups, and thus unconsciously associates the flavour of the supplement with this positive change, which will be measured in their acceptance response.

The innovation phase focuses on development and testing of new protein enriched food prototypes. First through a qualitative approach potentially interesting directions for product development are identified, including the types of foods senior consumers find suitable and acceptable for protein enrichment. Next step is a sensory driven product development.

Different strategies are evaluated to counteract the bitter taste of some kinds of proteins, so that the most sensory acceptable prototypes are further developed. Once actual prototypes are ready for evaluation by consumers, quantitative measurements are used to identify which prototypes are most liked by senior consumers, and thus are expected to have a chance of success among senior consumers in Denmark.

Finally, the effect of eating situation, intake, and satiety of the most acceptable prototypes are further investigated. By understanding the impact on Danish senior consumers, the new developed products will have a better chance of success when launched as commercial options.

The studies are carried out by the Department of Food Science at SCIENCE.

Metabolome characterization

The inhabitants of our gut are essential for a range of metabolic processes, such as the breakdown and absorption of energy from complex carbohydrates. In the same way, a number of human diseases are related to imbalances or changes in the composition of our gut microbiota, which in turn influence our metabolome.

Among the elderly, it has been found that the gut microbiota composition changes towards a higher proportion of facultative anaerobes and less bifidobacteria as compared to younger controls; these changes influence gut microbiota function and, consequently, human health and disease.

Diet is a major factor in shaping the human gut microbiota composition. Protein is primarily degraded and absorbed in the small intestine. Increased protein intake is likely to influence microbiota in the small intestine, which will impact the breakdown and absorption of other nutrients and hormone release, and also influence the microbial composition of the lower gastrointestinal tract and the overall metabolome as such.

The influence of exercise on the human gut microbiota is poorly understood, but as exercise has been found to positively influence peristaltic movement and to reduce the time-length of food passage in the gut, it is likely that exercise will also influence gut microbiota composition and gut microbiota–host interactions.

A detailed understanding of diet–exercise–gut microbiota–metabolome interactions is essential to recognising how age-related loss of muscle mass can be alleviated through changes in diet and exercise levels.

In recent years, there has been a massive development in high throughput sequencing (HTS) techniques and advanced bioinformatic and data-analysis tools, which has resulted in novel possibilities for investigating the relationship between gut microbiota and diet, disease, metabolome, etc., at a hitherto unseen level of detail.

Focus has primarily been on the prokaryotic (bacterial) members of our gut microbiota, but there is an emerging understanding that phages (i.e., a virus attacking bacteria) and eukaryotic (yeast and yeast-like) micro-organisms also play important roles in shaping the ecosystem of the human gut. Our present understanding of how dietary changes may influence the non-prokaryotic communities within the gut microbiota is scant, but this information could be potentially significant and promising for high-impact discoveries.

With the aim to obtain a detailed understanding of how increased protein intake and exercise levels influence gut microbiota composition and function, as well as how these changes interplay with the human metabolome, a detailed gut microbiota characterisation will be conducted and coupled with metabolome profiling of blood and urine.

The gut microbiota characterisation will be based on faecal samples from each volunteer enrolled in the intervention as outlined above, and colonoscopic biopsies of the small intestine taken from a limited number of volunteers.

Being able to profile the small intestine gut microbiota where protein breakdown and absorption take place is important in gaining a more complete understanding of the impact of increased protein intake on gut microbiota function.

Gut microbiota composition and function will be determined at baseline and after intervention at several levels: composition of the prokaryotic and eukaryotic communities will be determined using 454/FLX-based 16S and 26S rRNA gene-targeted, tag-encoded HTS sequencing: the phage (gut virome) composition will be determined via Illumina and 454/FLX-based HTS of CsCl ultracentrifugation-derived phage/virus fractions of faecal and, if possible, small-intestinal biopsies; and the gut metagenome in the subset of volunteers undergoing detailed testing for muscle increase will be analysed using Illumina-based HTS.

Furthermore, blood and urine samples from the volunteers (both baseline and after intervention) will be measured using high-field NMR metabonomics in order to determine the individuals’ full metabolic state. The spectral fingerprints of blood and urine will be analysed, explored and data-mined by applying state-of-the-art pre-processing tools for the alignment, together with modern data interpretation and multivariate pattern-recognition methods (chemometrics).

Finally, GM compositional data will be correlated to changes in the metabolome and other parameters, such as muscle strength, quality of life questionnaires etc. using bioinformatics and multivariate data-analysis competences.

2018

Even effect of milk protein and carbohydrate intake but no further effect of heavy resistance exercise on myofibrillar protein synthesis in older men
Forfattere: Reitelseder, S.; Dideriksen, K.; Agergaard, J.; Malmgaard-Clausen, N.M.; Bechshoeft, R.L.; Petersen, R.K.; Serena, A.; Mikkelsen, U.R.; Holm, L.
Artikel i Eur. J. Nutrition. 2018.

2017

Ældre menneskers liv og livsvilkår siden 1900
Forfattere: Jensen, T; Wingender, N,; Nørtoft, K, Lassen, AJ; Møller, A.
Kapitel i Gammel i København. Frydenlund. 2017

Eating Strategies. An analysis of how frail home-dwelling older people in Denmark develop strategies to form meaningful eating situations
Forfattere: Jensen, T.; Grønnow, L.; Jespersen, A.P.
Kapitel i Ageing & Society. Doi:10.1017/S0144686X70001076. 2017.

Getting Old and Keeping Going: The Motivation Technologies of Active Aging in Denmark
Forfattere: Lassen, A.J. & Jespersen, A.P.
Kapitel i Lamb, Sarah (ed.): "Successful Aging? Global Perspectives on a Contemporary Obsession", Rutgers University Press. 2017.

Improved skeletal muscle mass and strength after heavy strength training in very old individuals 
Forfattere: Bechshoeft, R.L.; Malmgaard-Clausen, N.M.; Madsen, B.G.; Beyer, N.; Mackey, A.L.; Andersen, J.L.; Kjaer, M.; Holm, L.
Exp. Gerontology. 92, 96-105, 2017.

Resistance training in elderly people: The influence of training load and age on muscle mass and function
Phd afhandling af Bechshoeft, R.L.
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen. 2017.

Towards understanding the trajectory and interactions of the gut microbiome in healthy older humans
Phd afhandling af Castro-Mejia, J.L.
Department of Food Science, Faculty of Science, University of Copenhagen. 2017.

Sundhedsfremme for pensionister gennem forståelse af deres hverdagsrutiner
Forfatter: Lassen, AJ.
Artikel i Københavns Universitets Almanak 2018. 2017.

Hvorfor er styrketræning vigtig for ældre?
Forfattere: Larsen, MM and Lassen, AJ.
Artikel i Seniorbladet, 5:7, 12-13, 2017.

Ny forskning skal opdage sarkopeni
Forfattere: Larsen, MM and Lassen, AJ.
Artikel i Seniorbladet, 5:7, 14-16, 2017.

Proteiner er livsnødvendige
Forfattere: Larsen, MM and Lassen, AJ.
Artikel i Seniorbladet, 5:8, 14-16, 2017.

2016

Counteracting age-related loss of skeletal muscle mass : a clinical and ethnological trial on the role of protein supplementation and training load (CALM Intervention Study): study protocol for a randomized controlled trial
Forfattere: Bechshøft, Rasmus; Reitelseder, Søren; Højfeldt, Grith; Castro Mejia, Josue Leonardo; Khakimov, Bekzod; Bin Ahmad, Hajar Fauzan; Kjær, Michael; Engelsen, Søren Balling; Laugesen, Susanne Margrete Bølling; Rasmussen, Morten Arendt; Lassen, Aske Juul; Jensen, Tenna; Beyer, Nina; Serena, Anja; Perez-Cueto, Armando; Nielsen, Dennis Sandris; Jespersen, Astrid Pernille; Holm, Lars
Artikel I Trials, 2016, Vol. 17, 397
Læs artiklen (pdf)

Extraction and purification of viruses from fecal samples for metagenome and morphology analyses
Forfattere: Castro-Mejia, J.L.; Deng, L.; Vogensen, F.K.; Reyes, A.; Nielsen
Artikel i “Methods in Molecular Biology: The human virome”, Springer. 2016

Changes in orosensory perception related to aging and strategies for counteracting its influence on food preferences among older adults
Forfattere: Song, Xiao; Giacalone, Davide; Laugesen, Susanne Margrete Bølling; Frøst, Michael Bom; Bredie, Wender
Artikel i Trends in Food Science & Technology, 2016, Vol. 53, p. 49-59
Læs artiklen på sciencedirect.com (kræver adgangskode)

Health and quality of life in an aging population – food and beyond
Forfattere: Giacalone, Davide; Wendin, Karin Maria Elisabet; Kremer, Stefanie; Frøst, Michael Bom; Bredie, Wender; Olsson, Viktoria; Otto, Marie Haulund; Skjoldborg, Signe Dahl; Lindberg, Ulla; Risvik, Einar.
Artikel i Food Quality and Preference, Vol. 47, No. Part B, 2016, p. 166-170.
Læs artiklen på sciencedirect.com (kræver adgangskode).

Implied meal partners. Ethnographic accounts of older research participants in a clinical intervention and their meal practices
Forfatter: Marie Haulund Otto
Artikel i Ethnologia Scandinavica. A Journal for Nordic Ethnology. Vol. 46, 2016. p. 87-104. 2016.

The importance of age perceptions and nutritional science to early 20th century institutional diets
Forfatter: Tenna Jensen
Artikel i Social History og Medicine. Online first. 2016.
Læs artiklen på academia.oup.com

Whey protein stories – an experiment in writing a multidisciplinary biography
Forfattere: Jensen, T.; Bechshøft, RL.; Giacalone, D.; Otto, MH.; Castro-Mejía, J.; Ahmad HF.; Reitelseder, S.; Jespersen, AP.
Artikel i Appetite, 107: 285-294. 2016.
Læs artiklen på sciencedirect.com (begrænset adgang).

2015

Alder, mælkeprotein og muskelfunktion
Forfattere: Reitelseder, S.; Bechshøft, R.L.; Holm, L.,
Artikel i Mælkeritidende, 128(17), p. 8-9. 2015.
Læs artiklen på maelkeritidende.dk

Appetit på maden, Rapport og Idékatalog
Forfattere: Jensen, T.; Grønnow, L.; Larsen, M.; Eisner, N.; Toft, C.; Jespersen, A.P.
Læs rapporten Appetit på Maden (pdf).

Hurrah for the increasing longevity: feasible strategies to counteract age-related loss of skeletal muscle mass
Forfattere: Lars Holm ; Astrid Pernille Jespersen ; Dennis Sandris Nielsen ; Michael Bom Frøst ; Søren Reitelseder ; Tenna Jensen ; Søren Balling Engelsen ; M. Kjær ; Tine Damsholt
Artikel i Scandinavian Journal of Medicine & Science in Sports, Vol. 25. February 2015.
Læs artiklen på onlinelibrary.wiley.com

Optimizing protocols for extraction of bacteriophages prior to metagenomic analyses of phage communities in the human gut
Forfattere: Castro-Mejía, J.L.; Muhammed, M.K.; Kot, W.; Neve, H.; Franz, C.M.A.P.; Hansen, L.H.; Vogensen, F.K.; Nielsen, D.S.
Artikel i Microbiome, 3:64. 2015.
Læs artiklen (pdf)

Ældres hverdagspraksisser og aldringspolitik: Om synkroniseringsarbejdet imellem hverdag og politik
Forfattere: Lassen, A.J. & Jespersen, A.P.
Artikel i Kulturstudier, 1:79-99. 2015.
Læs artiklen på tidsskriftetkulturstudier.dk

2014

Det gode seniorliv
Forfattere: Lars Holm ; Astrid Jespersen ; Rikke Lund
Bog. Strandberg Publishing. 2014.
Bestil bogen på strandbergpublishing.dk

Mad til ældre i Danmark. Mangel og krig i tiden 1892-1945
Forfatter: Tenna Jensen
Artikel i Dansk Madhistorie: Mad i krig og krise. Redigeret af Irene Hellvik. Dansk Landbrugsmuseums Forlag. Nov. 2014.

Fra forfald til forbedring. Ændrede opfattelser af ældres sundhed i Danmark i det 20. århundrede
Forfatter: Tenna Jensen
Artikel i Tidsskriftet Kulturstuder, #1. Juli 2014.
Læs artiklen på tidsskriftetkulturstudier.dk

Unmaking old age: The political and cognitive formats of active aging
Forfattere: Lassen, A.J.; Moreira, T.
Artikel i Journal of Aging studies, 30: 33-46. 2014.
Læs artiklen på sciencedirect.com (begrænset adgang)