| 1. |
- de Magalhaes, J P, et al.
(författare)
-
Cognitive aging as an extension of brain development : A model linking learning, brain plasticity, and neurodegeneration
- 2005
-
Ingår i: Mechanisms of Ageing and Development. - : Elsevier BV. - 0047-6374 .- 1872-6216. ; 126:10, s. 1026-1033
-
Forskningsöversikt (refereegranskat)abstract
- Differences in cognitive aging rates among mammals suggest that the pace of brain aging is genetically determined. In this work, we investigate the possibility that brain aging is an extension of brain development. It is possible that a subset of developmental mechanisms are extreme cases of antagonistic pleiotropy in that they are necessary for reaching adulthood and yet later cause age-related diseases. We derive a model linking development and brain aging in which childhood events essential for brain development later result in neurodegeneration. The hypothesis presented herein involves brain plasticity in which the same mechanisms that shape the adult phenotype continue at later ages contributing to cognitive dysfunction and eventually dementia. The same genetic program that decreases brain plasticity at early ages to focus our mind to the surrounding environment may continue in adulthood resulting in cognitive aging. Experimental implications for understanding neurodegeneration in this context are also discussed. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
|
|
| 2. |
|
|
| 3. |
- Wikby, A, et al.
(författare)
-
The immune risk phenotype is associated with Il-6 in the terminal decline stage: Findings from the Swedish NONA immune longitudinal study of very late life functioning
- 2006
-
Ingår i: Mechanisms Ageing and Development. - : Elsevier. ; 127:8, s. 695-704
-
Tidskriftsartikel (refereegranskat)abstract
- In the present NONA immune longitudinal study, we further examine the previously identi-fied T cell immune risk phenotype (IRP), relative inflammatory activity, morbidity and 2-year mortality in very old individuals >90 years. T-cell subsets as well as the inflammatory mark-ers IL-6, IL-10, C-reactive protein, transthyretin and albumin were evaluated. IRP and low-grade inflammation predicted 57% of observed deaths and 97% of survival over 2 years, and was not significantly affected by individuals' health status, suggesting that the physiological ageing processes of T-cell immunosenescence and low-grade inflammation are of primary importance in late life survival. IRP non-survivors showed only a minor inflammatory activity at baseline, but had in contrast to survivors developed increased activity at follow-up. The re-sults suggest a sequence of stages for IRP individuals that begin with acquisition of CMV in-fection in earlier life, followed by generation of CD8+CD28- cells to control persistent CMV infection and eventually the development of an IRP. Intriguingly, we also found that rare in-dividuals moved out of the IRP category by a process of immune suppression, including in-creases in IL-6 and IL-10 and decreases in the number of CD3+CD8+CD28- cells. The fur-ther characterisation of these exceptional individuals may allow insight into remedial ap-proaches for those who remain in the IRP category until death
|
|
| 4. |
- Sjogren, M, et al.
(författare)
-
Frontotemporal dementia--a brief review
- 2006
-
Ingår i: Mechanisms of ageing and development. - : Elsevier BV. - 0047-6374. ; 127:2, s. 180-187
-
Tidskriftsartikel (refereegranskat)
|
|
| 5. |
- Sjögren, Magnus, et al.
(författare)
-
Cholesterol and Alzheimer's disease--is there a relation?
- 2006
-
Ingår i: Mechanisms of ageing and development. - : Elsevier BV. - 0047-6374. ; 127:2, s. 138-47
-
Forskningsöversikt (refereegranskat)abstract
- The predominating theory on the pathophysiology of Alzheimer's disease (AD) concerns the mis-metabolism of amyloid precursor protein (APP). As a result of this mis-metabolism, there is an increased production of the 42 amino acid form of beta-amyloid (Abeta42) that rapidly will form oligomers that initiates a cascade of events leading to the accumulation of amyloid plaques. Commonly recognised as vascular factors, hypertension, hypercholesterolemia and diabetes and the inheritance of the epsilon4 allele of the APOE gene, are also risk factors for AD. These risks have been found to promote the production of Abeta42. An association between cholesterol and the development of AD was suggested in the early 1990s and ever since, an increasing amount of research has confirmed that there is a link between cholesterol and the development of AD. A high cholesterol levels in mid-life is a risk for AD and statins, i.e., cholesterol-lowering drugs, reduce this risk. Statins may not only inhibit enzymes involved in the endogenous synthesis of cholesterol but also affect enzymes involved in Abeta metabolism, i.e., alpha-secretase and beta-secretase. This normalises the breakdown of APP thereby promoting the non-amyloidogenic pathway. In this review, investigations focusing on cholesterol and Alzheimer's disease are presented.
|
|
| 6. |
|
|
