Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Between destiny and disease: genetics and molecular pathways of CNS aging

Glorioso, Christin Ann (2010) Between destiny and disease: genetics and molecular pathways of CNS aging. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

Primary Text

Download (37MB) | Preview


Human brain aging is associated with robust "normal" functional, structural, and molecular changes that underlie changes in cognition, memory, mood and motor function, amongst other processes. Normal aging is also a requirement for onset of many neurological diseases, ranging from later onset neurodegenerative diseases such as Alzheimer's(AD) and Parkinson's diseases(PD), to earlier onset psychiatric disorders such as bipolar disorder(BPD) and schizophrenia(SCHZ). Understanding the molecular mechanisms and genetic underpinnings of normal age-related brain changes would have profound consequences for prevention and treatment of age-related impairments and disease. Here I introduce current knowledge of these functional changes, their structural and molecular underpinnings, their genetic modulators, and the contribution of normal aging to age-related neurological disease. I then present my contribution to this field in the form of three papers on genetic modulation of mammalian brain molecular aging. These studies demonstrate and investigate mechanisms underlying the causal modulation of molecular brain aging rates by Brain Derived Neurotrophic Factor (BDNF) and Serotonin (5-HT) in knock-out (KO) mice, and associative modulation by the putative longevity gene, Sirtuin 5, in humans (novel low-expressing promoter polymorphism (Sirt5prom2)). In humans we additionally investigate the potential mechanism(s) underlying neurological disease gating by normal aging, providing supporting evidence for molecular aging being a genetically controlled "transcriptional program" that progressively promotes age-regulated neurological diseases. In the discussion, I place these studies in a broader context within the field, detailing their implications and future directions.


Social Networking:
Share |


Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Glorioso, Christin
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairZigmond, Michaelzigmond@pitt.eduZIGMOND
Committee MemberBradberry,
Committee MemberSibille,
Committee MemberTorres, Gonzalogtoreres@pitt.eduGTORERES
Committee MemberGianaros,
Committee MemberKim,
Date: 20 April 2010
Date Type: Completion
Defense Date: 17 March 2010
Approval Date: 20 April 2010
Submission Date: 1 April 2010
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Neurobiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: bdnf; biosignature; brain aging; human; microarray; Parkinson's disease; serotonin; sirtuin
Other ID:, etd-04012010-142303
Date Deposited: 10 Nov 2011 19:33
Last Modified: 15 Nov 2016 13:38


Monthly Views for the past 3 years

Plum Analytics

Actions (login required)

View Item View Item