of the candidate --Lisa M. Larkin obtained a Ph.D. from the University of California, Davis in January 1993 where she majored in Nutrition and metabolism and minored in Neurophysiology. Her Ph.D. dissertation involved studies on the effect of aging on skeletal muscle glucose metabolism. Her primary research interest is the effect of aging on skeletal muscle metabolism. The candidate has spent the last three years completing a postdoctoral fellowship in the institute of Gerontology at the University of Michigan where she continued to investigate the effect of age on the metabolic function of skeletal muscle. In collaboration with Dr. John Faulkner, the candidate investigated post-surgical alterations in skeletal muscle metabolism which could explain the observed decreased functional ability of the grafted muscle. The candidate's future research goal is to develop new expertise and to apply the knowledge obtained from these young-grafted muscles to investigate the ability for senescent- grafted muscle to rehabilitate after surgical procedures. This MRSDA will allow the candidate to continue her career development by establishing herself as an independent investigator with unique understanding of age- related changes both in skeletal muscle metabolism and in the ares of muscle contractile mechanics, muscle microneurovascular grafting and regeneration, and chronic electrical stimulation which are critical to successful rehabilitation after microneurovascular grafting in muscle. Description of the environment -- Dr. Lisa M. Larkin will have access to the expertise and facilities of three mentors and two consultant to ensure athe success of this proposal: Dr. Halter (glucose metabolism and aging), Dr. Faulkner (muscle mechanics and aging), Dr. Supiano (adrenergic receptor function and aging), Dr. Kuzon (functional and metabolic characteristics in muscle grafts), and Dr. Galecki (biostatistician). Further assistance and educational opportunities will be provided by the faculty of the Institute of Gerontology and the Claude Pepper Older Americans Independence Center at the University of michigan which maintain a Core facility for Aged Rodents (CFAR). In addition, the candidate will have access to the faculty and facilities of the Geriatric Research, Education, Clinical Center, VAMC. Description of the research -- Microneurovascular grafting could be a potentially powerful method for th restoration of muscle function following loss of function in condition often found in the aging population such a regional muscle or nerve injury, surgery to remove malignant tumors, stroke, or central and peripheral nervous system disorders. Although the majority of morphological and physiological characteristics return to baseline following the grafting of whole skeletal muscle, subsequent restoration of specific force and resistance to fatigue is impaired. The inability of grafted muscle to achieve the specific fore and resistance to fatigue compromises the usefulness of the grafting procedure in the repair of muscle dysfunction. In addition, aging is associated with a decline in skeletal muscle strength and the resistance to fatigue. Determining the mechanism(s) responsible for the decrease in strength and endurance of aging and/or grafted skeletal muscle could help in the prevention and treatment of skeletal muscle disorders in the elderly. This proposed study will use an orthotopic microneurovascular graft of the medial gastrocnemius (MGN) muscle as a model to the examine the ability of senescent rats to sustain power following a whole muscle grafting procedure and to determine if the expected decrease in the ability to sustain power is due to an increased number of denervated muscle fibers, resulting in diminished metabolic capacity in the grafted muscle. In addition, the proposed study will examine the effectiveness of chronic low frequency electrical stimulation as an intervention to enhance rehabilitation of senescent MGN muscle from a microneurovascular grafting procedure.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Scientist Development Award - Research & Training (K01)
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Biological and Clinical Aging Review Committee (BCA)
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University of Michigan Ann Arbor
Internal Medicine/Medicine
Schools of Medicine
Ann Arbor
United States
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Reynolds 4th, Thomas H; Reid, Pamela; Larkin, Lisa M et al. (2004) Effects of aerobic exercise training on the protein kinase B (PKB)/mammalian target of rapamycin (mTOR) signaling pathway in aged skeletal muscle. Exp Gerontol 39:379-85
Reynolds 4th, Thomas H; Krajewski, Katherine M; Larkin, Lisa M et al. (2002) Effect of age on skeletal muscle proteolysis in extensor digitorum longus muscles of B6C3F1 mice. J Gerontol A Biol Sci Med Sci 57:B198-201
Larkin, L M; Reynolds, T H; Supiano, M A et al. (2001) Effect of aging and obesity on insulin responsiveness and glut-4 glucose transporter content in skeletal muscle of Fischer 344 x Brown Norway rats. J Gerontol A Biol Sci Med Sci 56:B486-92
Larkin, L M; Kuzon Jr, W M; Halter, J B (2000) Synergist muscle ablation and recovery from nerve-repair grafting: contractile and metabolic function. J Appl Physiol 89:1469-76
Larkin, L M; Halter, J B; Supiano, M A (1996) Effect of aging on rat skeletal muscle beta-AR function in male Fischer 344 x brown Norway rats. Am J Physiol 270:R462-8