There is an unbounded amount of research work that might be performed to investigate methods of modestly slowing aging in mice. Doing no more than exploring the surrounding biochemistry related to mTOR might be enough to occupy most of the researchers capable of this work for a decade. The open access paper I'll point out today is an example of the type: the authors picked one of the scores of proteins identified as having a closer relationship to mTOR and its biochemistry, and spent several person-years of time and funding learning something about its role.This type of project could easily be multiplied a hundredfold, across dozens of teams, and that would still capture only a fraction of the state space to be explored. Cells are complicated.
The research community will explore all of that state space in the fullness of time. This activity isn't, however, a cost-effective path towards meaningful therapies that might address aging in humans. That isn't even the goal of this research, though it is a useful flag to wave from time to time when seeking funding. The primary goal is to map all of mammalian metabolism, to fully understand its operation - knowledge is the motivation of pure science, not application of knowledge. Whenever researchers state in public that human life extension is only a distant prospect, they are thinking in terms of the time taken to gather a fairly complete understanding of cellular metabolism, and then on top of that the time taken to build a new metabolism that functions more efficiently and ages less rapidly.
This is why I am much in favor of the SENS rejuvenation research approach to aging. The strategy there is to keep the metabolism we have, the one we don't fully understand, but that nonetheless works well enough while we are young, and periodically repair the known forms of root cause damage that make it run awry to produce degenerative aging. This way of looking at the problem bypasses the need to fully understand cellular metabolism, and even bypasses the need to fully understand exactly how the root cause damage produces aging. Thus a much smaller set of challenges in this line of work relate to planning, building, and executing successful repair therapies, while disrupting cellular biochemistry as little as possible. Via this path, it is possible to talk about significantly turning back aging within our lifetimes.
Mutant mice hold back the years
Biologists have created mice that live longer and appear to age more slowly than ordinary mice. In previous work, researchers developed mice with a mutation that reduces the animals' production of a protein called C/EBPβ-LIP. This mutation conferred metabolic benefits similar to those achieved by limiting calorie intake, which is known to extend lifespan in some animals.
The team's new experiments show that female mice with the mutation lived approximately 10% longer than ordinary mice, and were less susceptible to cancer. As females aged, those with the mutation gained less weight and maintained better overall motor skills. Both male and female mice with reduced C/EBPβ-LIP were more resistant to age-related changes in the immune and metabolic systems, compared with control animals.
Reduced expression of C/EBPβ-LIP extends health- and lifespan in mice
Ageing is associated with physical decline and the development of age-related diseases such as metabolic disorders and cancer. Few conditions are known that attenuate the adverse effects of ageing, including calorie restriction (CR) and reduced signalling through the mechanistic target of rapamycin complex 1 (mTORC1) pathway. Synthesis of the metabolic transcription factor C/EBPβ-LIP is stimulated by mTORC1, which critically depends on a short upstream open reading frame (uORF) in the Cebpb-mRNA.
Here we describe that reduced C/EBPβ-LIP expression due to genetic ablation of the uORF delays the development of age-associated phenotypes in mice. Moreover, female mice engineered in this way display an extended lifespan. Since LIP levels increase upon aging in wild type mice, our data reveal an important role for C/EBPβ in the aging process and suggest that restriction of LIP expression sustains health and fitness. Thus, therapeutic strategies targeting C/EBPβ-LIP may offer new possibilities to treat age-related diseases and to prolong healthspan.
View the full article at FightAging
