A publicity release has been doing the rounds and a number of people have pointed it out to me in the past day, something that usually only tends to happen for items much more interesting than this one. The release covers research into J147, a drug candidate for Alzheimer's disease that has been under investigation in animal studies for the past few years. It has now been tested in the SAMP8 lineage of engineered mice that suffer from accelerated aging, and the researchers are touting a slowing of that acceleration of aging as measured by cognitive decline and changes in gene expression. As is often the case, omissions and oversimplification of necessary details occurred somewhere between the lab and the publicity office, and as a consequence people are paying more attention to this research than it merits. The most important of these omissions is the fact that J147 was tested on an accelerated aging mouse lineage; without that detail, the publicity release makes the research sound much more useful than it is.
Researchers frequently start work in animal models that have been altered to allow for shorter studies. The cost of these studies is large in comparison to working with cells, so being able to cut that cost in half, for example, by using an accelerated aging lineage is often worth it. Mouse studies can cost millions and take years, and a million dollars goes a long way in early stage research; there are always other projects that need funding. Unfortunately when it comes to research potentially relevant to aging this use of accelerated aging lineages usually means that the results are very technical in nature and largely meaningless for anyone trying to judge whether not the outcome is useful. The literature is littered with examples of researchers slowing the progression of - or partly reversing - accelerated aging by somewhat fixing the issue that caused that accelerated aging, and then later finding that their work had little to no effect on the progression of normal aging. Part of the problem here is that there really is no such thing as "accelerated aging." Aging is an accumulation of cell and tissue damage, yes, and what looks like accelerated aging can be created by piling on damage, such as by interfering with DNA repair mechanisms. But the end result bears only a tenuous relationship to the progression of normal aging, and once you're down to the detail level of building therapies based on manipulating specific cellular mechanisms it is unlikely that benefits to an accelerated aging lineage also accrue in the same way for a normal aging lineage.
There are always exceptions. Senescent cell clearance was first demonstrated in accelerated aging mice, and then later showed the same sort of benefits in normal mice. In that case there were good technical reasons and a weight of evidence to lead researchers to expect that the results would carry over. That isn't something that a layperson can be expected to wade through for every line of research, however. The exceptions to the general rule are infrequent enough that, personally, I'd advise people to just ignore published research results in accelerated aging mouse lineages. The press invariably makes much more of it than it is worth, and most of this work loses any possible relevance to normal aging as it progresses. It never hurts to wait and see rather than get excited over this sort of result.
Below find excerpts from the publicity materials and open access paper for the latest research into the effects of J147, and judge for yourself the poor quality of the release materials when it comes to representing the nature of the research. It is an undeniably interesting set of results, but this is something that I'd want to see repeated in normal mice before paying any great attention to it. In fact I'd be inclined to see this more in the way of a trial balloon to gather support for the longer and more expensive lifespan study in normal mice that might be carried out next:
Research expanded upon their previous development of a drug candidate, called J147, which takes a different tack by targeting Alzheimer's major risk factor - old age. In the new work, the team showed that the drug candidate worked well in a mouse model of aging not typically used in Alzheimer's research. When these mice were treated with J147, they had better memory and cognition, healthier blood vessels in the brain and other improved physiological features. "Initially, the impetus was to test this drug in a novel animal model that was more similar to 99 percent of Alzheimer's cases. We did not predict we'd see this sort of anti-aging effect, but J147 made old mice look like they were young, based upon a number of physiological parameters."
The old mice that received J147 performed better on memory and other tests for cognition and also displayed more robust motor movements. The mice treated with J147 also had fewer pathological signs of Alzheimer's in their brains. Importantly, because of the large amount of data collected on the three groups of mice, it was possible to demonstrate that many aspects of gene expression and metabolism in the old mice fed J147 were very similar to those of young animals. These included markers for increased energy metabolism, reduced brain inflammation and reduced levels of oxidized fatty acids in the brain. Another notable effect was that J147 prevented the leakage of blood from the microvessels in the brains of old mice.
One model of aging is the senescence-accelerated prone 8 (SAMP8) mouse, that has a progressive, age-associated decline in brain function similar to human AD patients. As they age, SAMP8 mice develop an early deterioration in learning and memory as well as a number of pathophysiological alterations in the brain including increased oxidative stress, inflammation, vascular impairment, gliosis, Aβ accumulation and tau hyperphosphorylation.
Because age is the greatest risk factor for sporadic Alzheimer's disease (AD), phenotypic screens based upon old age-associated brain toxicities were used to develop the potent neurotrophic drug J147. Since certain aspects of aging may be primary cause of AD, we hypothesized that J147 would be effective against AD-associated pathology in rapidly aging SAMP8 mice and could be used to identify some of the molecular contributions of aging to AD.
An inclusive and integrative multiomics approach was used to investigate protein and gene expression, metabolite levels, and cognition in old and young SAMP8 mice. J147 reduced cognitive deficits in old SAMP8 mice, while restoring multiple molecular markers associated with human AD, vascular pathology, impaired synaptic function, and inflammation to those approaching the young phenotype. The extensive assays used in this study identified a subset of molecular changes associated with aging that may be necessary for the development of AD.