The multi-disciplinary and translational VOILA project presents a unique intersection between gut, immuno-metabolic, and musculoskeletal health. The main goals of the project are to develop biomarkers for healthy aging and prevent disease by maintaining quality of life in older adults. Within this umbrella project, the multimodal VOILA lifestyle intervention study will assess the impact of a twelve-week strength training and nutritional intervention in older adults with different degrees of mobility. The study will improve the current understanding of the complex relationship between gut and muscle health in different segments of mobility and obtain an insight into the heterogeneity of responsiveness between individuals.

Inclusion Criteria:

• Age ≥70 years
• A body mass index of 18.5-35.0 kg/m2
• Able to give written informed consent
• Community-dwelling
• Mentally competent with a Mini-Mental State Examination (MMSE) score of ≥24 points
• Able to follow the study protocol

Additional group-specific criteria:

Metabolically compromised group

- Framingham Risk Score ≥14 and Metabolomic Mortality Score of ≥0.173

Reduced mobility group - People able to walk but needing walking aids to walk anywhere outside their house

Total knee replacement intervention and control group

- Discharged from MUMC+ after undergoing elective knee replacement surgery (intervention starts ~4 weeks after surgery)

Active reference group

• People who meet the "Nederlandse Norm Gezond Bewegen". This means they partake in at least moderate exercise for at least 30 minutes on 5 days of the week, as determined by the SQUASH questionnaire (40).
• Framingham Risk Score of <14 and Metabolic Mortality Score of <0.173

Exclusion Criteria:

• Already using prebiotic fibres*
• Use of laxatives*
• Not willing to stop using dietary supplements in high doses (high doses: 0.10*Upper Level or more)*
• Following a structured, intense exercise programme (currently or in the last year)*
• Allergic, intolerant or hypersensitive to milk/lactose (self-reported)*
• Dietary restrictions on milk/lactose/prebiotics/vitamin D/calcium consumption*
• Abnormal hepatic or renal laboratory parameters (estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 (screening) or contra-indication by treating medical practitioner (data from hospital)
• Diagnosis of disorders/diseases in which a high protein intake can be harmful, such as renal impairment or failure, liver disease, or diabetes associated with nephropathy (treating medical practitioner has the decisive voice).
• Diseases, conditions or disorders which may affect the ability to follow the study protocol and which cannot be overcome with help of a caregiver Any other medical condition that may interfere with the safety of the participants during training or assessment of the outcome parameters, in the investigators' judgement
• Current participation in other scientific research that conflicts with this study (e.g. intervention studies or weight management studies)
• Not signed up to a general practitioner
• No permission to request information from the general practitioner/ treating specialist(s) about medical history, medication use.

Specific for TKR group:

• Referral to rehabilitation facility after hospital discharge
• Osteoarthritis of the knee secondary to septic arthritis, osteonecrosis, fracture, osteochondritis dissecans, or malignant processes
• Collagen disorders, e.g. Marfan and Ehler-Danlos
• Total hip prosthesis or TKR in both legs

Clinical data in this project will only be shared within the constraints of the informed consent. Furthermore for all permitted sharing, a data access committee (DAC) has been established in which the responsible PI of each center is present, a secretary and data manager. The data will primarily be analysed by the centers generating the data and associated partners in the VOILA project. In a later stage data access can be requested at the central contact person P.E. Slagboom (p.slagboom@lumc.nl ) and permitted by the DAC and analysed locally provided a data access agreement is signed.

Length is not determined.