Energetic cost of biosynthesis modulates the growth-longevity tradeoff in mice: Quantitative insights into four lifespan-altering manipulations.

Life history theory proposes a tradeoff between growth rate and lifespan, typically explained by the allocation of limited energy resources between somatic growth and maintenance. However, this explanation does not give a complete picture of the energy tradeoff. This study investigates two energy allocation mechanisms that influence growth and longevity simultaneously: the redirection of metabolic energy from growth to maintenance under energy limitation, and increased energy investment in biosynthesis, enhancing bio-tissue quality and stress resistance but also slowing growth. By analyzing empirical data from laboratory mice subjected to diet restriction (DR), dwarfism through genetic manipulations (Dwarf), rapamycin treatment (Rap), and growth hormone transgenics (Super), we quantify changes in growth rate, metabolic rate, and biosynthesis energy costs (E). Our quantitative analyses demonstrate that although both mechanisms slow growth and extend lifespan, they work differently depending on the type of manipulation. In DR, Dwarf, and Rap mice, these mechanisms act synergistically, significantly enhancing lifespan. These manipulations not only channel more energy from growth to somatic maintenance but also increase the energy investment to biosynthesis and therefore enhance the tissues' ability of resisting stress. Conversely, in Super mice, the mechanisms partially counteract each other. In this case, the treatment drains energy from somatic maintenance to growth, but slightly increases energy investment to biosynthesis, resulting in less pronounced effects on longevity. These findings suggest that the energetic cost of biosynthesis, a previously underappreciated factor, critically influences the balance between growth rate and lifespan, providing deeper insight into life history evolution and aging mechanisms.