Monday, January 25, 2021

Aging is Contagious within the Body

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In the midst of a discussion regarding the limitations of life span studies, in that the use of death as an endpoint fails to capture all of the variances in health due to aging, the authors of this paper offer up the thought that aging is contagious within the body. Declines in one cell spread to another, directly or indirectly. Consider that the secretions of senescent cells can make nearby cells senescent. Declines in one tissue can spread to another, directly or indirectly. Consider that the progressive failure of kidney function produces cardiovascular and cognitive dysfunction as a result, because the vascular system and the brain are so very dependent on the environment that the kidney is primarily responsible for maintaining. What might we take from this line of thinking? Perhaps that every form of repair therapy can be helpful, and equally that any one form of repair might not be enough, and the details matter in every case.

Given the complex heterogeneities of cell and tissue aging in any single individual and the notion of the most rapidly aging tissues being the driver of the aging of that organism, do those more rapidly aging tissues accelerate the aging of other tissues in the body? Does the aging of one cell affect the age of another cell? Is aging contagious? The notion of the aging process spreading from one cell to another is highlighted by the field of cellular senescence. The secretome of senescent cells has been shown to induce senescence of neighboring cells. In that sense, there can be cellular leaders that accelerate the aging of other cells in the tissue.

The notion of cell-to-cell spreading of cellular dysfunction is of course not limited to the biology of senescence. This is becoming an increasingly recognized phenomenon in the pathogenesis of neurodegenerative diseases. In many diseases, including Alzheimer's disease, Huntington's disease and Parkinson's disease, a cardinal feature of the pathology is intracellular aggregation of proteins. While seemingly a cell-intrinsic phenomenon, one of the curious features of the pathology of these diseases is the apparent spread of the cellular abnormalities to anatomically connected brain regions.

The general concept of this kind of spreading proteinopathy from one cell to another, locally, arises from the biology of prions and prion diseases. Of course, some prions are truly contagious, in the sense of being transmissible between individuals or across species, but the spread within the central nervous system of an individual suggests cell-to-cell spread. As with senescence, this phenomenon could represent the conversion of cells from one state (free from aggregates) to another (aggregate-laden) since protein aggregation can be self-propagating. As protein aggregation is one of the key features of cellular aging, it is intriguing to consider the possibility of aged cells achieving a sufficiently dysfunctional state as a result of protein aggregation, then conferring an aging signal to nearby cells through non-cell autonomous regulation of proteostasis.

If aging is indeed contagious, is the spread restricted to neighboring cells or might it spread to distant tissues via the systemic circulation? Based on early work from our laboratories that ushered in a new era of the use of the technique of parabiosis in aging research, it is clear that systemic factors originating from distant tissues in the body are able to either promote or reverse cell and tissue aging phenotypes. These findings, as well as many follow-up studies, including the demonstration that plasma infusions alone are sufficient to exert these effects, have unequivocally demonstrated that factors in the blood are able to communicate information from one or more source tissues to other tissues throughout the body. These could potentially accelerate, delay, or even reverse the rate of aging of other tissues in the body. Indeed, studies of brain endothelial cell aging showed that infusion of aged plasma can accelerate while young plasma can reverse aging as determined by analysis of the transcriptome. These studies highlight the fact that cellular aging does not occur independent of influences that are both local and systemic.

Link: https://doi.org/10.1038/s43587-020-00015-1

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source https://www.fightaging.org/archives/2021/01/aging-is-contagious-within-the-body/

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