The research I'll note today involves genetic knockout of fatty acid-binding proteins in mice, something that appears to slow the development of metabolic disorders associated with excess fat tissue and aging - there is a lot more funding for investigation of the former cause as opposed to the latter cause, sadly. The work is, I think, chiefly interesting for mimicking some of the cellular effects of calorie restriction, while preventing some degree of the metabolic decline that accompanies aging, but achieving all of this without either extending life or improving the other usual functional measures of aging: loss of strength, cognitive decline, and so forth. In principle that sort of result should be quite hard to achieve, and indeed I can think of few lines of research in which this happens with any reliability in short-lived species such as mice. They are sensitive to environmental and genetic interventions, with very plastic life spans in comparison to those of longer-lived species such as our own. Anything that constitutes a significant improvement to health should also extend life.

Extending the duration of measures of health without extending life span is hard precisely because aging is determined by cell and tissue damage, a consequence of that damage, just like the decline of any complex machinery. There are only a few options when it comes to how to proceed: fix the root cause damage, try to compensate for loss of function by adding more capacity, or try to prevent secondary effects that result from the primary damage. Medicine to date has focused on the latter two options, which is precisely why it produces only marginal, incremental benefits. Making a damaged machine work well without repairing the damage is exactly as challenging as it sounds.

The genetic intervention carried out by the researchers in this paper has the look of a method of preventing secondary effects, some of those resulting from weight gain and fat tissue dysfunction in aging, by interfering in the processing of fats. That is no doubt an overly simplistic consideration. For example, we know that simple surgical removal of visceral fat significantly extends life span in mice, and yet the genetic approach here, that reduces weight gain, has no such outcome. A first thought is that it is possible that removal of fatty acid-binding proteins is causing harm in other areas of biochemistry, and thus shortening life even as it helps on the metabolic front. So while the researchers discuss their data as evidence of a decoupling of metabolic health and life span, and make a fair case, it may or may not be what is happening under the hood.

Targeting 'lipid chaperones' may hold promise for lifelong preservation of metabolic health

Uncoupling of Metabolic Health from Longevity through Genetic Alteration of Adipose Tissue Lipid-Binding Proteins