# Maternal α-casein deficiency extends the lifespan of offspring and programmes their body composition

## TL;DR

A deficiency in maternal alpha-casein protein leads to smaller, longer-living offspring with altered body composition.

## Contribution

The study reveals that maternal alpha-casein deficiency permanently alters offspring's body composition and lifespan through early-life nutritional programming.

## Key findings

- Offspring of alpha-casein deficient dams have a 20% longer lifespan compared to controls.
- These offspring show reduced body weight, adipose tissue, and serum leptin levels.
- Early-life nutrition alters adult lipid metabolism and body composition permanently.

## Abstract

Early nutrition has significant effects on physiological outcomes during adult life. We have analysed the effect of maternal α-casein (CSN1S1) deficiency on the physiological fate of dams and their offspring. α-casein deficiency reduces maternal milk protein concentration by more than 50% and attenuates the growth of pups to 27% (p < 0.001) of controls at the point of weaning. This is associated with a permanent reduction in adult body weight (− 31% at 25 weeks). Offspring nursed by α-casein deficient dams showed a significantly increased lifespan (+ 20%, χ2: 10.6; p = 0.001). Liver transcriptome analysis of offspring nursed by α-casein deficient dams at weaning revealed gene expression patterns similar to those found in dwarf mice (reduced expression of somatotropic axis signalling genes, increased expression of xenobiotic metabolism genes). In adult mice, the expression of somatotropic axis genes returned to control levels. This demonstrates that, in contrast to dwarf mice, attenuation of the GH-IGF signalling axis in offspring nursed by α-casein deficient dams is transient, while the changes in body size and lifespan are permanent. Offspring nursed by α-casein deficient dams showed permanent changes in body composition. Absolute and relative adipose tissue weights (p < 0.05), the percentage of body fat (p < 0.001) as well as adipocyte size in epididymal white adipose tissue are all reduced. Serum leptin levels were 25% of those found in control mice (p < 0.001). Liver lipid content and lipid composition were significantly altered in response to postnatal nutrition. This demonstrates the nutrition in early life programmes adult lipid metabolism, body composition and lifespan.

The online version contains supplementary material available at 10.1007/s11357-024-01273-2.