The coming decades will be marked by a """"""""graying"""""""" of the United States population. The most rapidly growing demographic group in the country is that of elderly persons, and within this group, that of the """"""""oldest old."""""""" These trends pose significant challenges to our current medical practice. For example, the underlying causes of age-related behavioral changes remain undetermined. This application will examine the relationship between aging and changes in functional behaviors (eating, drinking, activity) by testing the hypotheses that (1) Age-related changes in mouse functional behaviors correlate with changes in gene expression regulating inflammatory and immune mediators, and (2) exercise and environmental enrichment improve CNS functional reserve by delaying or diminishing differential expression of genes regulating immune and inflammatory processes. We propose a cross-sectional study of young, middle-aged, and aged mice. Behaviors will be monitored using a state-of-the-art system that finely classifies large behavioral data streams in a reliable and automated fashion. Measures of overall behavior, including those of circadian rhythm, time budget, and properties (duration, frequency, etc.) of movement, feeding, and drinking bouts will be analyzed. Preliminary data find alterations in these measures similar to those seen in aging human populations. Additionally, gene expression in the hypothalamus and frontal cortex will be assessed using microarray and QT-PCR methods. Differentially expressed gene products will be classified by gene purpose. This will allow us to test whether observed behaviors correlate with changes in genes regulating immune responses rather than genes regulating activity, movement, and ingestive behaviors. We will also use graph-theory approaches to identify specific metabolic pathways (e.g., Atf3-Mapk8-Tlr2) altered in the aging hypothalamus. We also propose a longitudinal study to test whether lifestyle modifications including exercise and environmental enrichment increase CNS functional reserve. We will use similar measures of mouse behavior and gene expression as outcomes in this study. Ultimately, we anticipate that these data will provide important insight regarding the nature of aging processes in the brain, and may suggest important genetic targets for therapeutic manipulation.
Ultimately, it is anticipated that these data will provide important insight regarding the nature of aging processes in the brain, and may suggest important genetic targets for therapeutic manipulation.
|Chaudoin, Tammy R; Bonasera, Stephen J (2018) Mice lacking galectin-3 (Lgals3) function have decreased home cage movement. BMC Neurosci 19:27|
|DeKorver, Nicholas W; Lichty, Dustin; van der Hart, Marieke et al. (2017) Increased whole cerebellar serotonin in aged C57BL/6 mice. Matters (Zur) 2017:|
|Rye Hanton, Cassia; Kwon, Yong-Jun; Aung, Thawda et al. (2017) Mobile Phone-Based Measures of Activity, Step Count, and Gait Speed: Results From a Study of Older Ambulatory Adults in a Naturalistic Setting. JMIR Mhealth Uhealth 5:e104|
|DeKorver, Nicholas W; Chaudoin, Tammy R; Bonasera, Stephen J (2017) Toll-Like Receptor 2 Is a Regulator of Circadian Active and Inactive State Consolidation in C57BL/6 Mice. Front Aging Neurosci 9:219|
|Bonasera, S J; Chaudoin, T R; Goulding, E H et al. (2017) Decreased home cage movement and oromotor impairments in adult Fmr1-KO mice. Genes Brain Behav 16:564-573|
|Bonasera, Stephen J; Arikkath, Jyothi; Boska, Michael D et al. (2016) Age-related changes in cerebellar and hypothalamic function accompany non-microglial immune gene expression, altered synapse organization, and excitatory amino acid neurotransmission deficits. Aging (Albany NY) 8:2153-2181|
|Balas, Michele C; Bonasera, Stephen J; Cohen, Marlene Z et al. (2015) Measuring functional recovery in older patients discharged from intensive care units: is advanced technology an option? J Appl Gerontol 34:NP22-40|
|Volden, T A; Reyelts, C D; Hoke, T A et al. (2015) Validation of Flow Cytometry and Magnetic Bead-Based Methods to Enrich CNS Single Cell Suspensions for Quiescent Microglia. J Neuroimmune Pharmacol 10:655-65|
|Wan, Neng; Qu, Wenyu; Whittington, Jackie et al. (2013) Assessing Smart Phones for Generating Life-space Indicators. Environ Plann B Plann Des 40:350-361|
|Carlson Jr, Richard H; Huebner, Derek R; Hoarty, Carrie A et al. (2012) Treadmill gait speeds correlate with physical activity counts measured by cell phone accelerometers. Gait Posture 36:241-8|
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