L-serine and Strength Training in the Elderly

Change in cognitive domain performance measured by index scores of RBANS

The RBANS provides standardized index scores (mean = 100, standard deviation = 15) that typically range from approximately 40 to 160, with higher scores indicating better cognitive performance. The following RBANS domain indices will be evaluated: Immediate Memory Index, Visuospatial/Constructional Index, Language Index, Attention Index, and Delayed Memory Index.

Time frame: Baseline, 18 weeks and 48 weeks of intervention

Change in hippocampal volume measured by magnetic resonance imaging (mm³)

Time frame: Baseline and 48 weeks of intervention

Change in hippocampal functional connectivity measured by functional magnetic resonance imaging

Time frame: Baseline and 48 weeks of intervention

Change in oscillatory brain activity measured using electroencephalography

Time frame: Baseline, 18 weeks and 48 weeks of intervention

Change in hippocampal neurometabolite concentrations measured using single voxel magnetic resonance spectroscopy

Time frame: Baseline, 18 weeks and 48 weeks of intervention

Change in lower limb muscle strength (isokinetic torque, dominant leg)

Concentric isokinetic peak torque (in newton meters, Nm) will be assessed for knee extension, knee flexion, and hip extension and flexion using an Isoforce dynamometer (TUR GmbH, Hohen Neuendorf, Berlin). All isokinetic measurements will be performed on the dominant leg and with 4 consecutive repetitions at maximal effort of extension and flexion. Testing the knee will be performed over a range of motion (ROM) of 20 degrees-100 degrees at angular velocities of 60 degrees/s , and 180 degrees/s. Testing the hip will be performed over a range of motion (ROM) of 20 degrees- 90 degrees at angular velocities of 60 degrees/s , and 180 degrees/s. The minimum possible torque is 00 Nm; higher values indicate better muscle strength.

Time frame: Baseline, 18 weeks and 48 weeks of intervention

Rate of torque development (Nm/s) will be measured at a joint angle of 60 degrees flexion (knee) and 40 degrees flexion (hip).

Time frame: Baseline, 18 weeks and 48 weeks of intervention

Change in maximum and total work (J) of knee and hip flexion and extension

Time frame: Baseline, 18 weeks and 48 of intervention

Position of peak torque and maximum range of motion (deg.)

Time frame: Baseline, 18 weeks and 48 weeks of intervention

Change in time to peak torque and time from peak to relaxation (sec.) during knee and hip extension and flexion

Time frame: Baseline, 18 weeks and 48 weeks of intervention

Mean power (W) in knee and hip extension and flexion

Time frame: Baseline, 18 weeks, and 48 weeks of intervention

Change in isometric handgrip strength

Isometric handgrip strength will be measured in kilograms (kg) using a JAMAR-compatible handgrip dynamometer adjustable to different grip widths. Testing will be performed seated. Each trial consists of a maximal isometric contraction held for 4-5 seconds; two trials will be conducted with the dominant and subsequently with the non-dominant hand, with 1-2 minutes rest between trials. The minimum possible value is 00 kg; higher values indicate better grip strength. Results will be recorded per trial; the analysis will use the highest value from the two trials (peak grip strength, kg).

Time frame: Baseline, 18 weeks, and 48 weeks of intervention

Change in upper extremity functional performance measured by the 30-Second Arm Curl Test

The 30-Second Arm Curl Test assesses the number of full elbow-flexion repetitions completed in 30 seconds with a standardized dumbbell while seated. Women use a 5 lb (2.3 kg) dumbbell; men use an 8 lb (3.6 kg) dumbbell. Participant sits upright near the front edge of a chair without armrests, back straight, feet flat on the floor, holding the dumbbell in the dominant hand with a supinated grip. After instruction and demonstration, the participant performs 2-3 practice repetitions. Following a 60-second rest, the timed test begins on the assessor's signal. The starting position is full elbow extension (down); the end position is full elbow flexion (up). Count only repetitions that complete the full range of motion (ROM). A repetition initiated in the final second (second 30) is counted as valid if more than 50% of the ROM is completed. Minimum possible value is 0 repetitions; there is no predefined maximum.

Time frame: Baseline, 18 weeks, and 48 weeks of intervention

Change in upper-body flexibility (Back Scratch Test)

The Back Scratch Test assesses shoulder, shoulder-girdle, and thoracic spine flexibility. While standing, one hand is placed over the shoulder and down between the shoulder blades; the other hand reaches up the back. The linear distance between the tips of the middle fingers is measured along the spine using a tape measure. Record the distance in centimeters (cm) with sign convention: positive values indicate fingertip overlap; zero indicates fingertips just touch; negative values indicate a gap between fingertips. There is no predefined minimum or maximum (values can range from negative to positive depending on flexibility and anthropometrics). Higher (more positive) values indicate better flexibility. Back Scratch distance (cm), dominant side (specify side assessed in the protocol). Use the same side and method at all time points.

Time frame: Baseline, 18 weeks, and 48 weeks of intervention

Change in Lower body flexibility (Chair Sit and Reach Test)

The participant sits at the front edge of a stable chair placed against a wall (seat height approximately 45-46 cm). One leg is flexed at the knee with the foot flat on the floor; the other leg is extended at the knee with the ankle dorsiflexed to approximately 90 degrees. With the hands stacked (middle fingertips aligned), the participant inhales, then exhales while hinging at the hips to reach forward toward the toes of the extended leg, avoiding bouncing; the back stays straight and the head upright. The maximal position is held for about 2 seconds. The linear distance between the tip of the middle finger and the toes of the extended leg is measured along the lower limb/foot. Record the distance (cm) using the following convention-0 cm if fingertips just touch the toes; negative values if the fingertips do not reach the toes (gap); positive values if the fingertips reach past the toes (overlap). Perform two trials per leg; record the best value per leg.

Time frame: Baseline, 18 weeks, and 48 weeks of intervention

Change in lower extremity functional muscular performance measured by the 30-Second Chair Stand Test

The 30-Second Chair-Stand Test assesses functional muscular performance (strength × speed) of the lower extremities. Stable, armless chair at approximately 46 cm seat height, placed against a wall to prevent movement. Participants wear non-slip, flat footwear or are barefoot. Participant sits upright, feet flat on the floor, arms crossed over the chest. On the assessor's signal, the participant stands up fully (knee and hip extension) and sits down as many times as possible within 30 seconds without using the arms. Count only full stand-sit cycles completed through the full range of motion (ROM). A repetition initiated in the final second (second 30) is counted as valid if more than 50% of the ROM is completed. Number of valid chair-stands completed in 30 seconds. Minimum possible value is 0 repetitions; there is no predefined maximum. Higher values indicate better lower-extremity functional performance.

Time frame: Baseline, 18 weeks, and 48 weeks of intervention

Mobility and dynamic balance (Stand Up and Go Test)

The Stand Up and Go Test assesses dynamic lower extremity power, dynamic balance, and overall functional mobility/coordination. Stable chair placed against a wall, seat height approximately 43 cm; a cone/marker placed 2.4 m from the front edge of the chair; clear, unobstructed path. Participant starts seated, back upright, feet flat on the floor. On the assessor's signal, the participant stands up, walks 2.4 m to the cone, turns around the cone, walks back to the chair, and sits down again. Timing begins on the start signal and stops when the participant is fully seated. Testing is performed in usual footwear; use of any assistive device (if permitted) should be consistent across visits and recorded. Time to complete the task, measured in seconds (s) to at least 0.1 s precision. Minimum possible value is 0 s; there is no predefined maximum. Lower times indicate better mobility and balance (i.e., higher values indicate worse performance).

Time frame: Baseline, 18 weeks, and 48 weeks of intervention

Change in body composition measured by bioelectrical impedance analysis

Body composition will be assessed using bioelectrical impedance analysis (seca Hamburg seca mBCA515), including measures of fat mass, lean body mass, body mass, and body water .

Time frame: Baseline, 18 weeks, and 48 weeks of intervention

Change in waist, abdominal, hip circumference (cm)

Time frame: Baseline, 18 weeks, and 48 weeks of intervention

Change in oxidative stress marker such as malondialdehyde

The investigators will consider changes in plasma concentrations of oxidative stress marker such as malondialdehyde.

Time frame: Baseline, 18 weeks and 48 weeks of intervention

Change from baseline in inflammatory marker (e.g. IL-6, TNF-alpha)

The investigators will consider changes in plasma concentrations of inflammatory markers such as Interleukin 1 (IL-1), IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha

Time frame: Baseline, 18 weeks, and 48 weeks of intervention

Change from baseline in RNA and DNA gene expression

RNA and DNA gene expression will be assessed in response to the interventions.

Time frame: Baseline, 18 weeks, and 48 weeks of intervention

Change from baseline in chromosomal damage (number of micronuclei/1000 binucleated cells)

Chromosomal damage will be assessed in lymphocytes in response to the interventions.

Time frame: Baseline, 18 weeks, and 48 weeks of intervention

Change from baseline in the composition of gut-microbiota

Gene sequencing of the 16S rRNA on the stool samples are performed to identify the microbes down to genus level as well as the microbial diversity and relative abundance.

Time frame: Baseline, 18 weeks, and 48 weeks of intervention

Change from baseline in stool short-chain fatty acids (SCFAs)

The stool short-chain fatty acids (SCFAs) will be extracted and quantitatively analysed by gas chromatography.

Time frame: Baseline, 18 weeks, and 48 weeks of intervention

Change from baseline in the metabolomic response

The metabolomic response (ie all metabolites) to the interventions will be analyzed using both nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques. Patterns of metabolites will be evaluated with statistical techniques, ie discriminant analysis and principal component analysis.

Time frame: Baseline, 18 weeks, and 48 weeks of intervention

Change from baseline in the amino acid pattern

The plasma amino acid pattern will be assessed with HPLC-MS.

Time frame: Baseline, 18 weeks, and 48 weeks of intervention

Nutritional habits

Evaluation of potential changes in nutritional habits (24 hours dietary recall) with GloboDiet

Time frame: Baseline, 18 weeks and 48 weeks of intervention

Change in sleep quality measured by the Pittsburgh Sleep Quality Index

Sleep quality will be assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. The PSQI global score ranges from 0 to 21, with higher scores indicating worse sleep quality.

Time frame: Baseline, 18 weeks, and 48 weeks

Change in quality of life measured by the World Health Organization Quality of Life Questionnaire

Quality of life will be assessed using the World Health Organization Quality of Life Questionnaire (WHOQOL). Scores range from 0 to 100, with higher scores indicating better perceived quality of life.

Time frame: Baseline, 18 weeks, and 48 weeks