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Kaufmann T, van der Meer D, Doan NT, Schwarz E, Lund MJ, Agartz I, Alnæs D, Barch DM, Baur-Streubel R, Bertolino A, Bettella F, Beyer MK, Bøen E, Borgwardt S, Brandt CL, Buitelaar J, Celius EG, Cervenka S, Conzelmann A, Córdova-Palomera A, Dale AM, de Quervain DJ, Carlo P, Djurovic S, Dørum ES, Eisenacher S, Elvsåshagen T, Espeseth T, Fatouros-Bergman H, Flyckt L, Franke B, Frei O, Haatveit B, Håberg AK, Harbo HF, Hartman CA, Heslenfeld D, Hoekstra PJ, Høgestøl EA, Jernigan TL, Jonassen R, Jönsson EG, Karolinska Schizophrenia Project (KaSP), Kirsch P, Kłoszewska I, Kolskår KK, Landrø NI, Hellard S, Lesch KP, Lovestone S, Lundervold A, Lundervold AJ, Maglanoc LA, Malt UF, Mecocci P, Melle I, Meyer-Lindenberg A, Moberget T, Norbom LB, Nordvik JE, Nyberg L, Oosterlaan J, Papalino M, Papassotiropoulos A, Pauli P, Pergola G, Persson K, Richard G, Rokicki J, Sanders AM, Selbæk G, Shadrin AA, Smeland OB, Soininen H, Sowa P, Steen VM, Tsolaki M, Ulrichsen KM, Vellas B, Wang L, Westman E, Ziegler GC, Zink M, Andreassen OA, Westlye LT. Common brain disorders are associated with heritable patterns of apparent aging of the brain. Nat Neurosci. 2019 Oct;22(10):1617-1623. Epub 2019 Sep 24 PubMed.
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Harvard Medical School
This interesting paper by Kaufmann and colleagues suggests that a number of common brain disorders are associated with potentially accelerated aging of the brain based on neuroimaging. By comparing the structure of control aging brains with those of patients, the authors compute a “brain age gap” that measures deviation from the norm. They find that the brain age gap is increased in several brain diseases, most notably in schizophrenia, multiple sclerosis, and dementia, and was associated with genetic variants that increase risk for these disorders. The central unanswered question is the mechanistic origins of the “brain age gap,” which are likely to be diverse. However, the genetic analysis of variant loci that are associated with the brain age gap reveals a discrete gene list with some loci appearing frequently. Interestingly, the most frequently detected locus is the SATB2 gene, coding a DNA binding protein that mediates attachment of DNA to the nuclear matrix. This is interesting because a number of neurodegenerative disorders, including Alzheimer’s disease, have been associated with disruption of the nuclear lamina. In addition, neuronal aging itself has been associated with reduced efficiency of nuclear-cytoplasmic transport and possible loss of nuclear membrane integrity.
A second significant locus was the SLC39A8 gene, a putative zinc transporter that has been implicated in inflammatory responses. This is intriguing in light of the evidence for a central role of inflammatory/immune responses in aging and neurological disorders, particularly Alzheimer’s disease. Hopefully future studies will determine if the age gap is a measure of parsimonious mechanisms that link neurological disorders to the biology of aging.
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