Fatigue and weakness are common complaints of elderly people related to sarcopenia, or the loss of skeletal muscle mass, organization, and strength. Little is known concerning the pathophysiology and age-related sequelae of sarcopenia in muscles of the head and neck. This knowledge is important inasmuch as alterations in muscle character may underlie deficits in speech and swallowing, which are significant clinical problems in elderly people. The tongue has a vital role in speech and swallowing, and poor lingual control is associated with both speech and swallowing impairment. However, muscles of the tongue have been understudied. Our hypothesis is that age-related alterations in tongue function are based upon naturally occurring denervation-reinnervation processes, and that these processes can be reversed or prevented via exercise. This hypothesis will be tested in a rat model by comparing physiological, molecular, and histological parameters of old rat tongue muscles with young muscles, and with old tongue muscles that have undergone chronic nerve stimulation to model exercise. The proposed research has 2 specific aims: (1) To quantify changes in neuromuscular morphology predictive of age-related tongue weakness; and (2) To determine underlying morphological and physiological changes induced by tongue exercise in old rats. Physiological experiments will be performed in vivo in the tongue in young rats and in 2 groups of older rats. In the same animals, molecular analyses of myosin heavy chain expression, and histological analyses of neuromuscular junctions will be performed. Exercise will be modeled via bilateral chronic stimulation of the hypoglossal nerves. Analyses of covariance (a combination of analysis of variance and regression) will be used to determine the degree to which muscle contractile properties can be predicted from molecular and histological characteristics. Further analyses of variance will be performed to compare the physiological, molecular, and histological variables of interest as a function of age group (Specific Aim 1) or age by exercise (Specific Aim 2). This work is innovative and important in establishing potential morphological bases for the alterations in physiological function observed with tongue muscle senescence. Further, this work will be highly significant in discovering a neuromuscular basis for the putative benefits of exercise in the prevention and treatment of age-related swallowing impairment.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC005935-04
Application #
6997863
Study Section
Special Emphasis Panel (ZRG1-BBBP-7 (01))
Program Officer
Shekim, Lana O
Project Start
2003-01-08
Project End
2007-12-31
Budget Start
2006-01-01
Budget End
2006-12-31
Support Year
4
Fiscal Year
2006
Total Cost
$282,398
Indirect Cost
Name
University of Wisconsin Madison
Department
Surgery
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Krekeler, Brittany N; Leverson, Glen; Connor, Nadine P (2018) Tongue exercise and ageing effects on morphological and biochemical properties of the posterior digastric and temporalis muscles in a Fischer 344 Brown Norway rat model. Arch Oral Biol 89:37-43
Kletzien, Heidi; Russell, John A; Leverson, Glen et al. (2018) Effect of neuromuscular electrical stimulation frequency on muscles of the tongue. Muscle Nerve 58:441-448
Kletzien, Heidi; Hare, Allison J; Leverson, Glen et al. (2018) Age-related effect of cell death on fiber morphology and number in tongue muscle. Muscle Nerve 57:E29-E37
Cullins, Miranda J; Krekeler, Brittany N; Connor, Nadine P (2018) Differential impact of tongue exercise on intrinsic lingual muscles. Laryngoscope 128:2245-2251
Krekeler, Brittany N; Broadfoot, Courtney K; Johnson, Stephen et al. (2018) Patient Adherence to Dysphagia Recommendations: A Systematic Review. Dysphagia 33:173-184
Cullins, Miranda J; Connor, Nadine P (2017) Alterations of intrinsic tongue muscle properties with aging. Muscle Nerve 56:E119-E125
Krekeler, Brittany N; Connor, Nadine P (2017) Age-related changes in mastication are not improved by tongue exercise in a rat model. Laryngoscope 127:E29-E34
Pultorak, Joshua D; Kelm-Nelson, Cynthia A; Holt, Lauren R et al. (2016) Decreased approach behavior and nucleus accumbens immediate early gene expression in response to Parkinsonian ultrasonic vocalizations in rats. Soc Neurosci 11:365-79
Kletzien, Heidi; Russell, John A; Connor, Nadine P (2016) The effects of treadmill running on aging laryngeal muscle structure. Laryngoscope 126:672-7
Glass, Tiffany J; Connor, Nadine P (2016) Digastric Muscle Phenotypes of the Ts65Dn Mouse Model of Down Syndrome. PLoS One 11:e0158008

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