Vitality Oriented Innovation for the Lifecourse of the Ageing Society - Intervention Study

Age is the most prominent risk factor for common diseases and multi-morbidity.
And yet it is the biological age of individuals even more than their
chronological age that influences such risk. The diversity in functioning
within the population of older adults suggests that various factors influence
biological age, resulting in substantial differences in (patho)physiological
state and disease risk between individuals of the same chronological age
(heterogeneity). Prominent drivers of biological age have been found in
pathways of energy metabolism and balance (metabolic health), chronic
inflammation and immunity and a central role for muscle and gut health
influencing biological age. Mobility is a major determinant of these drivers
and the physiological state of older people.
Combined lifestyle interventions are expected to beneficially influence
multiple aspects of biological age but the large heterogeneity of older adults
often obscures the effect of interventions. Hence, in order to slow down the
biological ageing process via preclinical or clinical interventions, it is
necessary to first study the effect of human interventions on diverse health
segments of older adults as well as individual older adults. This would allow
for a better understanding of biological factors that explain the heterogeneity
in responses often observed and could eventually lead to interventions better
tailored to segments and individuals.

With our proposed multimodal human lifestyle intervention study, containing
dietary and exercise components, we aim to improve (combinations of)
immuno-metabolic health (blood glucose, glycoprotein acetyls, very low density
lipoprotein diameter), gut-health (bifidobacteria), muscle mass (appendicular
lean mass) and physical functioning (5-times chair stand test) in three
different segments of older adults with varying degrees of compromised mobility
or metabolism (>=60 years of age), to study the difference in responsiveness
between mobility segments and heterogeneity in responsiveness of individuals
both within and between mobility segments.

The parallel, partially random (only in TKR groups) intervention will have a
duration of 12 weeks and includes 3 different intervention groups of older
adults segmented primarily by functional and metabolic status, a control group
of the knee replacement segment, and an active, community-dwelling reference
group representing the healthiest older adults.

The intervention consists of a combined exercise and nutritional intervention.
All participants will perform 12 weeks of supervised whole-body resistance type
exercise training; leg press, leg extension, calf raises, chest press, shoulder
press, horizontal row and vertical lateral pull exercise will be performed on
weightlifting machines, 3 days per week. The dietary intervention aims to
attain a diet that comprises sufficient protein (1.5 g/kg bodyweight/day,
distributed as 25-30 g protein per main meal, as well as a pre-sleep intake
moment), vitamin D (800 IU/day), calcium (366 mg/day), and prebiotics and is
otherwise in line with the Dutch Healthy Diet guidelines. To this end,
participants will receive nutritional counselling and will ingest a
protein-vitD-calcium-prebiotic product with breakfast, and a protein-calcium
product before sleep.

The intervention groups perform a supervised resistance type exercise program
three times per week, ingest nutritional prototypes twice daily and implement
adjustments of the general diet to increase protein intake and adhere to
general healthy eating guidelines for a total intervention period of 12 weeks.
These types of diets combined with exercise generally benefit muscle, gut and
immuno-metabolic health in older adults and have been assessed to be safe in
general. People for whom this is contraindicated (e.g. with kidney disease) are
excluded. Exercise training bears small risks of injury which will be mitigated
by employing trained professionals and executed one-to-one or in small groups
suitable to the populations, with individual adjustment of the intensity of the
program. It is possible that participants may experience light muscle soreness
induced by unaccustomed exercise, especially at the start of the program.
All groups will have the following measurements taken thrice (screening,
baseline and endpoint measurements): fill out questionnaires and undergo
venepunctures for blood samples, weight and height measured. The following will
be collected twice (baseline, endpoint): collect stool samples, wear
accelerometers, fill out a dietary record, have their waist circumference
measurement taken, perform physical function tests, receive a dual X-ray
absorptiometry scan, have their blood pressure taken and fill in several
questionnaires. The risk of complications from drawing blood is small and
samples will be drawn by trained professionals. There are no complications
associated with the procedure of a DXA scan. The level of radiation emitted
during a DXA is merely a fraction of that emitted during a regular chest X-ray.
All other measurements take time but are not associated with any risks and will
be done under supervision.*