Turning Over the Hourglass

Abstract

Richard K Shields, PT, PhD, has contributed to the physical therapy profession as a clinician, scientist, and academic leader (Fig. 1).

Dr Shields is professor and department executive officer of the Department of Physical Therapy and Rehabilitation Science at the University of Iowa. He completed a certificate in physical therapy from the Mayo Clinic, an MA degree in physical therapy, and a PhD in exercise science from the University of Iowa.

Dr Shields developed a fundamental interest in basic biological principles while at the Mayo Clinic. As a clinician, he provided acute inpatient care to individuals with spinal cord injury. This clinical experience prompted him to pursue a research career exploring the adaptive plasticity of the human neuromusculoskeletal systems. As a scientist and laboratory director, he developed a team of professionals who understand the entire disablement model, from molecular signaling to the psychosocial factors that impact health-related quality of life. His laboratory has been continuously funded by the National Institutes of Health since 2000 with more than 15 million in total investigator-initiated support. He has published 110 scientific papers and presented more than 300 invited lectures.

A past president of the Foundation for Physical Therapy, Dr Shields is a Catherine Worthingham Fellow of the American Physical Therapy Association (APTA) and has been honored with APTA’s Marian Williams Research Award, the Charles Magistro Service Award, and the Maley Distinguished Research Award. He also received the University of Iowa's Distinguished Mentor Award, Collegiate Teaching Award, and the Regents Award for Faculty Excellence.

Dr Shields is a member of the National Advisory Board for Rehabilitation Research and serves as the liaison member on the Council to the National Institute for Child Health and Human Development.

Figures

Figure 1.

Richard Shields, PT, PhD, presenting the 48th Mary McMillan Lecture at APTA’s NEXT Conference & Exposition, June 22, 2016, in Boston, Massachusetts. Photo credit: David Braun Photography Inc.

Figure 2.

“As a physical therapist, I believe that we change time. We routinely turn over the hourglass and give patients a new lease on life. Quite simply, our interventions… are powerful regulators of genes that activate the energy systems that can reduce the rate that cells and tissues age.” Photo credit: David Braun Photography Inc.

Figure 3.

Exercising skeletal muscles secrete powerful endocrine molecules called myokines into the blood. Myokines help regulate a number of important target tissues including the brain, creating an important link between habitual physical activity, biological aging of cells and tissues, and the onset of chronic disease.

Figure 4.

Core scientific principles for the physical therapy profession that govern the capacity for cells to respond to movement-based interventions.

Figure 5.

Mr J as a champion high school wrestler (top left), with Dr Shields in 1986 after sustaining C6 complete tetraplegia (bottom left), and after achieving independent mobility in a manual wheelchair (right).

Figure 6.

Conceptual relationship between movement dose, human performance, and health value. Compared with a person without a disability (orange plot), Mr J required a higher dose of movement to experience improvements in his human performance capacity (blue plot). However, he rapidly experienced improved health value (green plot), even given his delayed timetable for improvements in human performance. The conceptual relationship and figure are adapted from Gabriel BM, Zierath JR. The limits of exercise physiology: from performance to health. Cell Metab. 2017;25:1000–1011, with permission from Elsevier.

Figure 7.

Skeletal muscle size is determined by a balance between expression of hypertrophy gene pathways and atrophy gene pathways. After inactivity or injury, expression of atrophy genes increases many-fold. Epigenetic “tagging” may cause persistent up-regulation of these atrophy genes, even after restoration of normal activity. For some patients, persistent atrophy may implicate continued up-regulation of atrophy-promoting genes.

Figure 8.

Representative example of a gene-array “heat map” for a patient with spinal cord injury who engaged in two doses of a movement intervention. Dark, medium, and light purple represent high, moderate, and low levels of gene up-regulation, respectively. Dark, medium, and light green represent high, moderate, and low levels of gene down-regulation, respectively. White represents no change from the pretraining baseline. Appropriately dosed movement interventions strongly up-regulate peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1 alpha), a “master” gene that exerts widespread effects on gene networks that regulate cell metabolism. Through a multitude of downstream pathways, PGC1 alpha promotes mitochondrial replication and function, telomere length preservation, and epigenetic tagging of metabolic genes. ATP = adenosine triphosphate.

Figure 9.

Illustration of epigenetic regulation of the genome. Epigenetic “tagging” of DNA can either block or enhance the transcription of genes and the production of encoded proteins.

Figure 10.

Simplified adaptation of data from a recent report that established leukocyte telomere length in a large cohort of healthy men and women of various ages. The authors identified a “telomere brink,” a telomere length threshold below which the probability of survival substantially declined. Although not shown on this simplified plot, it is important to note that due to natural variation, telomere length varies widely among individuals of the same age.

Figure 11.

Conceptual relationship between mortality risk and various biomarkers of metabolic health: gene methylation, systemic metabolic markers, and telomere length. Optimally dosed movement interventions can reduce mortality risk by improving one or all of these metabolic biomarkers.

Figure 12.

Preliminary data from our laboratory indicate that after spinal cord injury, the strong up-regulation of PGC1 alpha observed with an appropriately-dosed movement intervention is associated with up-regulation of gene pathways associated with telomere function. (See Fig. 8 for gene array interpretation information.) RNA = ribonucleic acid, DNA = deoxyribonucleic acid.

Figure 13.

Mr. P after hemicorporectomy (left) and after receiving a socket prosthesis and manual wheelchair (right). Reprinted with permission of the American Physical Therapy Association from Shields RK, S Dudley-Javoroski. Musculoskeletal deterioration and hemicorporectomy after spinal cord injury. Phys Ther. 2003;83:263–275.

Figure 14.

Selected measurements from the University of Iowa Department of Physical Therapy and Rehabilitation Science annual benchmarking analysis. (A) Debt reported by Iowa graduating physical therapy students, compared with debt reported to the professional organizations of other health professions (see text for references). (B-D) The Department administers a slightly modified version of the Association of American Medical Colleges (AAMC) Graduation Questionnaire, then benchmarks to the mean of all medical education programs nationwide. (B) Physical therapist versus medical student ratings of anatomy curriculum. (C) Physical therapist versus medical student perceptions of faculty professionalism. (D) Physical therapist versus medical student reports of student mistreatment. Iowa PT = University of Iowa Department of Physical Therapy, d/t = due to.