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Systems genetics identifies Hp1bp3 as a novel modulator of cognitive aging
- Source :
- Neurobiology of aging 46, 58-67 (2016). doi:10.1016/j.neurobiolaging.2016.06.008
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- An individual's genetic makeup plays an important role in determining susceptibility to cognitive aging. Identifying the specific genes that contribute to cognitive aging may aid in early diagnosis of at-risk patients, as well as identify novel therapeutics targets to treat or prevent development of symptoms. Challenges to identifying these specific genes in human studies include complex genetics, difficulty in controlling environmental factors, and limited access to human brain tissue. Here, we identify Hp1bp3 as a novel modulator of cognitive aging using a genetically diverse population of mice and confirm that HP1BP3 protein levels are significantly reduced in the hippocampi of cognitively impaired elderly humans relative to cognitively intact controls. Deletion of functional Hp1bp3 in mice recapitulates memory deficits characteristic of aged impaired mice and humans, further supporting the idea that Hp1bp3 and associated molecular networks are modulators of cognitive aging. Overall, our results suggest Hp1bp3 may serve as a potential target against cognitive aging and demonstrate the utility of genetically diverse animal models for the study of complex human disease.
- Subjects :
- Male
0301 basic medicine
Cognitive aging
Aging
genetics [Cognition Disorders]
physiology [Cognitive Aging]
Limited access
Mice
Cognition
0302 clinical medicine
genetics [Memory Disorders]
Conditioning, Psychological
Fear conditioning
genetics [Genetic Predisposition to Disease]
Systems genetics
Mice, Knockout
BXD
Human studies
General Neuroscience
physiology [Cognition]
Nuclear Proteins
Fear
Human brain
medicine.anatomical_structure
genetics [Aging]
Female
physiology [Conditioning, Psychological]
Psychology
Gene set enrichment analysis
Neuroscience(all)
psychology [Cognition Disorders]
Clinical Neurology
Article
03 medical and health sciences
Memory
physiology [Nuclear Proteins]
HP1BP3 protein, mouse
medicine
Animals
Humans
Genetic Predisposition to Disease
ddc:610
physiology [Memory]
Gene
Genetic Association Studies
Memory Disorders
Disease Models, Animal
Ageing
030104 developmental biology
psychology [Memory Disorders]
Neurology (clinical)
Geriatrics and Gerontology
Cognition Disorders
Neuroscience
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- ISSN :
- 01974580
- Volume :
- 46
- Database :
- OpenAIRE
- Journal :
- Neurobiology of Aging
- Accession number :
- edsair.doi.dedup.....94aaecff282a498ab10cfdd7e79cc7d8
- Full Text :
- https://doi.org/10.1016/j.neurobiolaging.2016.06.008