Blood only partly reflected metabolism in five organs of mice receiving life-extending interventions
Blood only partly reflected metabolism in five organs of mice receiving life-extending interventions
In an article published on August 25, researchers compared plasma, the liquid component of blood, with the liver, kidneys, gastrocnemius muscle, and two types of adipose tissue from genetically heterogeneous UM-HET3 laboratory mice. From four to twelve months of age, the animals received calorie restriction or one of four drugs: rapamycin, canagliflozin, 17-alpha-estradiol, or acarbose. These regimens had extended lifespan in previous mouse experiments. Similarity between plasma and tissue depended on the organ, regimen, and sex.
Blood can be collected repeatedly from a living animal, so researchers use its composition to infer metabolic activity within organs. Plasma contains a mixture of substances derived from food, organs, and gut microbes. Direct measurements in the relevant organ are needed before such an analysis can show what happened in that organ.
In human studies, levels of the molecule NAD+ in whole blood changed after nicotinamide riboside supplementation but showed little response to age, exercise, or diet. The authors of the new article examined which tissue changes induced by life-extending regimens were also detectable in blood.
In a 2025 study, lipids were the class of compounds that changed most markedly across six sample types. The new article examines which of these changes can be linked to a specific tissue through plasma measurements.
For each tissue, 33–37% of the annotated metabolites were also detected in plasma. Metabolites are small molecules involved in metabolism. Each tissue shared a different set of molecules with plasma, so the plasma profile represented partial overlap with several organs.
After statistical testing to filter out chance differences, the authors identified 260 compounds that changed in both plasma and at least one tissue under one of the regimens. Ergothioneine, a dietary compound, changed in the same direction under several regimens in blood, muscle, liver, kidney, and subcutaneous adipose tissue. Lipids containing docosahexaenoic acid, an omega-3 fatty acid, changed consistently in blood and both adipose tissues. Another candidate, 1,5-anhydroglucitol, changed in the same direction in blood, liver, and kidneys under regimens that produced substantial lifespan extension. The authors found more groups of related molecules with consistent responses in males than in females.
In this mouse model, a useful blood biomarker must be linked to a specific tissue, regimen, and sex. Repeated blood tests become more informative once this relationship has been established through direct measurements in the organs.