David A. Loeffler, Andrea C. Klaver, Mary P. Coffey, Jan O. Aasly
Abstract
Autophagy removes both functional and damaged intracellular macromolecules from cells via lysosomal degradation. Three autophagic mechanisms, namely macroautophagy, chaperone-mediated autophagy (CMA), and microautophagy, have been described in mammals. Studies in experimental systems have found macroautophagy and CMA to decrease with normal aging, despite the fact that oxidative stress, which can activate both processes, increases with normal aging. Whether autophagic mechanisms decrease in the human brain during normal aging is unclear. The primary objective of this study was to examine the association of a major autophagy protein, lysosome-associated membrane glycoprotein (lamp2), with age in cerebrospinal fluid (CSF) samples from healthy subjects. Lamp2 consists of three isoforms, lamp2a, 2b and 2c, all of which participate in autophagy. Lamp2's CSF concentration decreases in Parkinson's disease (PD) and increases in Alzheimer's disease (AD), but whether its CSF concentration changes during normal aging has not been investigated. Our secondary objectives were to examine the associations of lamp2's CSF concentration with CSF levels of the molecular chaperone heat shock 70-kDa protein (HSPA8), which interacts with lamp2a in CMA, and oxidative stress markers 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-isoprostane (8-ISO) and Total Antioxidant Capacity (TAC) in healthy subjects. We found lamp2's observed associations with these variables to be weak, with all Kendall's tau-b absolute values ≤0.20. These results suggest that CSF lamp2 concentration changes little during normal aging and does not appear to be associated with HSPA8 or oxidative stress. Further studies are indicated to determine the relationship between CSF lamp2 concentration and brain autophagic processes.
Pharmacology, Toxicology and Pharmaceutical Science
1
6%
Business, Management and Accounting
1
6%
Other
3
18%
Unknown
3
18%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 10. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 June 2018.
All research outputs
#3,601,846
of 26,399,279 outputs
Outputs from Frontiers in Aging Neuroscience
#1,743
of 5,694 outputs
Outputs of similar age
#67,380
of 345,280 outputs
Outputs of similar age from Frontiers in Aging Neuroscience
#56
of 108 outputs
Altmetric has tracked 26,399,279 research outputs across all sources so far. Compared to these this one has done well and is in the 85th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,694 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.7. This one has gotten more attention than average, scoring higher than 67% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 345,280 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 80% of its contemporaries.
We're also able to compare this research output to 108 others from the same source and published within six weeks on either side of this one. This one is in the 47th percentile – i.e., 47% of its contemporaries scored the same or lower than it.
