Circadian cycles shift as humans get older—sleep and body temperature patterns change, for instance. The rhythmic cycling of numerous genes’ expression in the brain also shifts as people age, researchers reported this week (December 21) inPNAS. The levels of many transcripts became less robust in their daily ups and downs, while another set of mRNAs emerged with a rhythmicity not seen in younger counterparts.
“You can imagine that things actually get weaker with age, but that things can get stronger with age is really exciting,” Doris Kretzschmar, a neuroscientist at the Oregon Institute of Occupational Health Sciences who was not involved in the study, told NPR’s Shots.
The researchers, led by Colleen McClung at the University of Pittsburgh School of Medicine in Pennsylvania, collected cortical tissue from people whose hour of death was known. Comparing gene expression levels between 31 subjects under 40 years old and 37 subjects over age 60, the researchers found 1,063 transcripts in one part of the prefrontal cortex that lost rhythmicity altogether in the older group. In this same part of the brain, 434 genes gained a rhythm that was not seen among younger individuals. In another part of the prefrontal cortex, 588 genes lost their daily cycling with age, while 533 became rhythmic.
It’s not clear what these changes in expression cycles might mean for health and aging. “Since depression is associated with accelerated molecular aging, and with disruptions in daily routines, these results also may shed light on molecular changes occurring in adults with depression,” coauthor Etienne Sibille of the University of Toronto said in a press release.
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This is very insightful. There is no doubt that there is the bias you refer to. 42 years ago, when I was postdocing in biochemistry/enzymology before completing my residency in pathology, I knew that there were very influential mambers of the faculty, who also had large programs, and attracted exceptional students. My mentor, it was said (although he was a great writer), could draft a project on toilet paper and call the NIH. It can’t be true, but it was a time in our history preceding a great explosion. It is bizarre for me to read now about eNOS and iNOS, and about CaMKII-á, â, ã, ä – isoenzymes. They were overlooked during the search for the genome, so intermediary metabolism took a back seat. But the work on protein conformation, and on the mechanism of action of enzymes and ligand and coenzyme was just out there, and became more important with the research on signaling pathways. The work on the mechanism of pyridine nucleotide isoenzymes preceded the work by Burton Sobel on the MB isoenzyme in heart. The Vietnam War cut into the funding, and it has actually declined linearly since.
A few years later, I was an Associate Professor at a new Medical School and I submitted a proposal that was reviewed by the Chairman of Pharmacology, who was a former Director of NSF. He thought it was good enough. I was a pathologist and it went to a Biochemistry Review Committee. It was approved, but not funded. The verdict was that I would not be able to carry out the studies needed, and they would have approached it differently. A thousand young investigators are out there now with similar letters. I was told that the Department Chairmen have to build up their faculty. It’s harder now than then. So I filed for and received 3 patents based on my work at the suggestion of my brother-in-law. When I took it to Boehringer-Mannheim, they were actually clueless.