A team of researchers, including Dr. Tony Wyss-Coray, co-founder of Alkahest, has discovered that exposing young cells to aged blood causes their gene expression to become akin to aged cells.
Signaling cells to act older
We have known from the heterochronic parabiosis and plasmapheresis research performed by Dr. Irina Conboy’s lab and similar work done by Dr. Wyss-Coray’s lab that aged blood causes negative effects in human cells and is strongly linked to systemic aging, to the point that a proteomic clock can be created to judge someone’s biological age in much the same way as other biomarker-based clocks can .
However, the biochemical relationship between aged blood and aged gene expression has yet to be fully understood, and this new study goes a long way in explaining these changes. RNA analysis shows that hundreds or thousands of genes are altered, depending on cell type, and these cellular reactions vary wildly. Even cells that are only indirectly exposed to blood factors are shown to have altered gene expression.
Hepatocytes, the predominant cells of our liver, have 600 differentially expressed genes (DEGs) when exposed to aged blood; on the other hand, aged hepatocytes exposed to young blood have a thousand gene expressions restored to a more youthful state. Endothelial cells, the cells that line our blood vessels, have anywhere from 300 to 1,000 DEGs affected by aged blood, which suggests that plasmapheresis or another blood treatment may be able to have significant effects on our blood vessels.
Hematopoietic stem cells (HSCs), which are responsible for generating other blood cell types, along with the many tissue-resident immune cell types, such as T cells, B cells, and neutrophils, also have a thousand gene expressions altered by the presence of aged blood, and mesenchymal stromal cells (also known as mesenchymal stem cells, MSCs) are also significantly affected.
The researchers point out that this accelerated aging has much in common with normal aging. 60% of the changes that occur in MSCs due to exposure to aged blood are identical to that of normal aging, and these percentages are 80% for HSCs and a full 94% for oligodendrocytes, which provide critical functions in the central nervous system.
A warning against obesity
In its discussion of blood proteins, this study has an unexpected warning about the accumulation of excess visceral fat, a metabolically active type of fat that surrounds organs. As we age, visceral fat produces the pro-aging blood protein CCL11, which is singled out in this study as being systematically harmful.
One thing that this study makes very clear is that the exact biological relationship between blood and aged gene expression will require significant effort to fully understand, and it is likely that advanced algorithms and data analysis will be employed in examining this relationship in each cell type.
However, this research appears to offer us a direct, if difficult, path to a therapy that will induce partial rejuvenation in human beings at the gene expression level. If we are able to safely replace the pro-aging factors in our blood with youthful ones, through plasmapheresis or another method, such a therapy could potentially provide a path to broad, systemic rejuvenation across a great many of our cells.
 Lehallier, B., Gate, D., Schaum, N., Nanasi, T., Lee, S. E., Yousef, H., … & Sathyan, S. (2019). Undulating changes in human plasma proteome profiles across the lifespan. Nature Medicine, 25(12), 1843-1850.
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