Many readers will recall the results of the past few years that claim that infusion of young-animal plasma into aged animals seems to have many beneficial effects. Of course, this field is well stocked with controversy. Not everyone believes the results, from what I can see (although, for what it’s worth, there seem to be an increasing number of papers on it). If they’re real, not everyone thinks that they can be readily extrapolated to humans. And even if they can, it doesn’t take very much thought to see a number of ethical implications as well.
There have been a couple of recent papers that will stir things up even more. This preprint from a multinational research team (UCLA and many others) details work on several “methylation clocks” of molecular aging. DNA is methylated (especially on cytosine residues) to a number of transcriptional effects, and the number and distribution of such methyl groups definitely change over the lifespan of most animals.
The Horvath lab at UCLA has made a specialty out of this epigenetic research area for some years now, and the changes in DNA methylation with aging seem pretty well established (even if quantifying them is trickier). This new paper draws on a large number of rat samples, with an overall methylation clock detailed, as well as more specific ones for brain, liver, and blood tissue. The addition of an even larger set of human tissue samples provides two more cross-species methylation clocks as well.
FULL TEXT: Science Translational Medicine
Age is the primary risk factor for the vast majority of disorders, including neurodegenerative diseases impacting brain function. Whether the consequences of aging at the biological level can be reversed, or age-related changes prevented, to change the trajectory of such disorders is thus of extreme interest and value.
Studies using young plasma, the acellular component of blood, have demonstrated that aging is malleable, with the ability to restore functions in old animals. Fascinatingly, this functional improvement is even observed in the brain, despite the blood-brain barrier, indicating that peripheral sources can effectively impact central sites leading to clinically relevant changes such as enhancement of cognitive function.
A plasma-based approach is also attractive as aging is inherently complex, with an array of mechanisms dysregulated in diverse cells and organs throughout the body leading to disturbed function. Plasma, containing a natural mixture of components, has the ability to act multimodally, modulating diverse mechanisms that can converge to change the trajectory of age-related diseases.
Here we review the evidence that plasma modulates aging processes in the brain and consider the therapeutic applications that derive from these observations. Plasma and plasma-derived therapeutics are an attractive translation of this concept, requiring critical consideration of benefits, risks, and ethics. Ultimately, knowledge derived from this science will drive a comprehensive molecular understanding to deliver optimized therapeutics. The potential of highly differentiated, multimodal therapeutics for treatment of age-related brain disorders provides an exciting new clinical approach to address the complex etiology of aging.
FULL TEXT: Neurotherapeutics