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Thursday, February 23, 2017

Ageing, neurodegeneration, and brain rejuvenation (NATURE INSIGHT REVIEW)



Abstract (as presented by the author of the scientific work):

"Although systemic diseases take the biggest toll on human health and well-being, increasingly, a failing brain is the arbiter of a death preceded by a gradual loss of the essence of being. Ageing, which is fundamental to neurodegeneration and dementia, affects every organ in the body and seems to be encoded partly in a blood-based signature. Indeed, factors in the circulation have been shown to modulate ageing and to rejuvenate numerous organs, including the brain. The discovery of such factors, the identification of their origins and a deeper understanding of their functions is ushering in a new era in ageing and dementia research."


Covered topics (the letter size corresponds to the frequency of mentioning in the text):



Outlook (as presented by the author of the scientific work):

"In humans, the old brain shows the classic hallmarks of ageing and is particularly susceptible to abnormal protein accumulation and impairments in the phagolysosomal system, which leads to fluid boundaries between ageing and neurodegenerative diseases. Consequently, many old people have pathological abnormalities of the brain that do not necessarily correlate with their cognitive abilities. This has important implications for the treatment of those with clinical symptoms as well as for designing clinical trials to target protein abnormalities in a specific manner. Given the crucial functions that immune responses and inflammation have in brain ageing and neurodegeneration, it will be essential to discern beneficial attempts to maintain or repair damage from maladaptive ones. Clearly, the term neuroinflammation fails to capture the age- or disease-related changes in this sophisticated interplay between the surveillance, identification, targeting and execution functions of immunity and should probably be avoided. When studying age-related neurodegenerative diseases in animal models, it is important to consider ageing; those that have been genetically engineered to develop disease during adolescence and before midlife are unlikely to be influenced sufficiently by ageing and are therefore not very informative about age-related factors in sporadic neurodegeneration.

The increasing number of studies that show systemic effects on the brain, including those of young plasma or heterochronic parabiosis, as well as the effects of the microbiome, should remind neuroscientists that neurons do not function in isolation; instead, they are part of a sophisticated network that includes glial cells, vascular cells and peripheral cells.

So far, there is no published evidence that young blood or plasma has beneficial effects on an ageing human body, and the observation that young plasma can modulate brain ageing in mice presents more questions and opportunities than answers. Only a handful of proteins, which might represent factors involved in ageing or rejuvenation, have been shown to mimic the effects of plasma. However, many more proteins or other types of molecules are likely to exist, some of which might have direct therapeutic applications. Basic research will address the exciting questions that surround the origins of these factors, how they signal to the brain and why they change with age. Ultimately, it is hoped that by using such knowledge to alter basic processes involved in ageing, it will become feasible to counter the cellular abnormalities that lead to neurodegeneration."


The referenced scientific work at PubMed:

Wyss-Coray T. Ageing, neurodegeneration and brain rejuvenation. Nature. 2016
Nov 10;539(7628):180-186. doi: 10.1038/nature20411. Review. PubMed PMID:
27830812; PubMed Central PMCID: PMC5172605.


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