The challenge when considering any study carried out in an accelerated aging animal model is whether or not the findings have any relevance to normal aging. Aging is at root the accumulation of molecular damage, but this is a specific balance of various forms of damage. Accelerated aging models pile on large amounts of one specific form of molecular damage, usually by suppressing DNA repair mechanisms. The results somewhat replicate the consequences of aging, but they are not aging. Thus one has to understand the fine details of the research in order to have an opinion on whether or not it tells us anything useful about normal aging. This isn't easy for laypeople; even scientists in the field can differ on these matters.
The study here is an example of the type, and a case in which I am not familiar enough with the mechanisms involved to be able to say whether or not the work is helpful. The approach taken by the researchers could just be addressing an aspect of the damage specific to the animal model rather than damage that occurs in aging. Researchers use accelerated aging models because they provide answers more rapidly and at a lower cost. The next step is to take the approach and try it out in normal mice, to see whether or not the results seem similar. It is a good idea to reserve judgement until those results are in hand.
Increasing age is the greatest known risk factor for the sporadic late-onset forms of neurodegenerative disorders such as Alzheimer's disease (AD). One of the brain regions most severely affected in AD is the hippocampus, a privileged structure that contains adult neural stem cells (NSCs) with neurogenic capacity. Hippocampal neurogenesis decreases during aging and the decrease is exacerbated in AD, but the mechanistic causes underlying this progressive decline remain largely unexplored.
We here investigated the effect of age on NSCs and neurogenesis by analyzing the senescence accelerated mouse prone 8 (SAMP8) strain, a non-transgenic short-lived strain that spontaneously develops a pathological profile similar to that of AD and that has been employed as a model system to study the transition from healthy aging to neurodegeneration. We show that SAMP8 mice display an accelerated loss of the NSC pool that coincides with an aberrant rise in BMP6 protein, enhanced canonical BMP signaling, and increased astroglial differentiation.
In vitro assays demonstrate that BMP6 severely impairs NSC expansion and promotes NSC differentiation into postmitotic astrocytes. Blocking the dysregulation of the BMP pathway in vivo by intracranial delivery of the antagonist Noggin restores hippocampal NSC numbers, neurogenesis, and behavior in SAMP8 mice. Thus, manipulating the local microenvironment of the NSC pool counteracts hippocampal dysfunction in pathological aging. Our results shed light on interventions that may allow taking advantage of the brain's natural plastic capacity to enhance cognitive function in late adulthood and in chronic neurodegenerative diseases such as AD.