It has been quite a number of years since researchers first produced dwarf mice with disabled growth hormone or growth hormone receptors, some of which still hold the record for engineered mouse longevity. Using these mice as a point of comparison to further map metabolism and aging continues to be an ongoing process, as illustrated by this open access paper. In it, the authors discuss the role of just one of many regulatory genes that might be important in many of the methods that have been used to slow aging in mice.

Cellular biochemistry is enormously complex, and thus so are the details of the changes that occur with aging, even though the underlying root causes are comparatively simple. As an analogy, consider what happens when a complicated metal assembly rusts into structural failure: rust is very simple, and that the assembly can ultimately fall apart in any one of many different ways is a function of the complexity of the structure, not of the rust. This is why attempting to slow aging by altering metabolism is so very hard and expensive, while attempting to reverse aging by repairing the root causes is comparatively straightforward and cost-effective. You can see that dynamic at work by comparing the little that has been achieved in twenty years of attempts to replicate the metabolic response to calorie restriction versus the solid progress achieved over the past five years of work on clearance of senescent cells. The latter has required a fraction of the cost and far fewer researchers than the former, while the results are already far more impressive.

Link: https://doi.org/10.1111/acel.12663