Forsøksdyr: Dietary impact on ageing - Nutrifrail

Godkjenningsdato 25.09.2020

Godkjenningsperiode 25.09.2020-24.09.2024

PURPOSE: The proportion of older people in Norway is rising. To keep the whole population as healthy as possible for as long as possible will minimize the socioeconomic burden for the society. In this study, we will study effects on aging by keeping mice up to 30 months of age and test if certain dietary factors or the diet compositions prevent or delay the progression of frailty and chronic diseases. These five different diets are: 1) low fat diet, 2) high fat diet, 3) high fat diet supplemented with 5% omega 3 fatty acids, 4) high fat diet with methionine restriction (0.17% Kcal%), 5) High fat diet with methionine restriction (0.17% Kcal%) and no added cysteine.
We will focus analysis on animal weight gain, energy metabolism and frailty, by performing home cage metabolic phenotyping, body mass composition (MRI), standard insulin, glucose and pyruvate tolerance tests, grip strength test and balance test using Rota Rod. According to §10, the purpose is: a) Basal Research.

DISTRESS: The whole study is rated “Moderate” due to repeated use of several methods with none/minor distress. Severity classification of procedures: 1) Blood sampling: Minimal. 2) Modified diets with altered energy composition that meets all nutritional requirements: Minimal. 4) Food withdraw for up to 16 hours: Minimal/moderate. 4) Metabolic Phenotyping: Minimal/moderate. 5) metabolic tolerance tests: Minimal/moderate. 6) Body composition measurements: Minimal. 7) grip strength test: Minimal. 8) Balance test on Rota Rod: Minimal/moderate. 9) altered diet composition: Minimal. The number of times each of the above procedure will be carried out on each animal varies from 1 up to 8 times. Mice will be exposed to short to medium food with draw prior to some of the above tests and euthanasia (to normalize blood glucose parameters). For additional details, see the method description.

BENEFITS: We expect that some of the diets will be healthier than others, e.g. the low fat diet and supplementation of the high fat diet with PUFA will be more beneficial than a high fat diet. Diets with methionine restriction (0.17% Kcal%) and no added cysteine have been shown to increase longevity and metabolic parameters, but it is less known how this diet affects frailty, muscle strength and balance. We expect this study to reveal clues about dietary factors that affect aging and frailty.

ANIMALS: We will include up to 400 mice during the next 4 years in this study. Each dietary group will start with 15 animals and we expect to start several cohorts that will age for a short (up to 6 months) or a long time (up to 30 months). The commonly used mice strain C57BL/6N will be used.

ADHERENCE TO 3Rs: The mice will be exposed to various methods that individually are categorized with none to moderate distress. There is therefore little room for improvements in the planned experimental procedures. Animal health will be monitored carefully. A score sheet will be used to identity mice that reaches the predefined humane endpoint, and such mice will be euthanized to minimize distress.