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京都大学 / 新制・課程博士 / 博士(医学) / 甲第23804号 / 医博第4850号 / 新制||医||1058(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 井上 治久, 教授 林 康紀, 教授 竹内 理 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

<p><strong>Introduction:</strong> Mitochondria are important organelles for skeletal muscle function. Mitochondria are susceptible to many forms of stress that alters their morphology, energy generation and reactive oxygen species (ROS) production, which collectively promote degeneration and dysfunction in skeletal muscle. These processes are implicated in many health disorders, particularly in the aging process itself. Exercise is well established to increase muscle mitochondrial content and thus may attenuate several aspects of mitochondrial deterioration. <strong>Methods:</strong> Both human and animal models of mitochondrial stress (aging, ROS) were utilized in order to determine their effects on mitochondrial and muscle function. Additionally, exercise training was used in order to assess its therapeutic potential in ameliorating defects in oxidative capacity, muscle atrophy and metabolic adaptation in skeletal muscle. <strong>Results:</strong> Aging resulted in reduced strength, aerobic capacity, larger intramyocelluar lipid droplets and fewer mitochondria in skeletal muscle. These changes were related to suppressed lipid metabolism, mitochondrial dynamics and organelle turnover. Habitual aerobic exercise partially attenuated the age-related loss of muscle strength and aerobic capacity, presumably due in part to improved mitochondrial function. Persistent mitochondrial oxidative stress prevented mitochondrial adaptations to exercise training in mice, a phenomenon that may explain why exercise cannot fully counteract the effects of aging in skeletal muscle. <strong>Conclusions and significance:</strong> This work furthers our knowledge of the mitochondrial consequences of aging and the therapeutic potential of aerobic exercise within skeletal muscle. These results can be applied to other differentiated tissues that are severely affected by aging (brain, heart) and the effects described here are likely relevant to other conditions that result in muscle atrophy and energetic insufficiency.</p> / Doctor of Philosophy (PhD)

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No / This paper provides the results of re-evaluation of a young adult individual from the Romano-British cemetery of 76 Kingsholm, Gloucester with club foot defomity by (Roberts et al 2004). Our reanalysis revealed an extensive bilateral asymmetry involving the lower and upper limb, spine and cranium and a right scoliosis, indicating more than the lower limb was affected. Consideration of the position and shape of the articulated club foot indicated a positional rather than a developmental condition, probably due to unilateral paralysis. Differential diagnosis considered congenital and acquired neuromuscular conditions; we argue that poliomyelitis is the most likely cause. Poliomyelitis is secondary to the infection with poliovirus that can affect the motor neurons from the spinal cord, causing a flaccid paralysis without sensory affection. Because the virus affects individual nerves, the paralysis is muscle-specific causing muscle imbalances and poor posture which can result in deformities and muscle disuse atrophy. Shortening of the leg is the most characteristic sign, however other typical deformations are in the lower limbs are external rotation of the knee, knee hyperestension, ankle and foot deformities (all observed in K131). The evaluation of K131’s entheses and bone structure suggests that, in life, this individual showed physical deformities consisting of a possibly visible atrophy of the left arm and leg, asymmetric gait, clubfoot and slight scoliosis which would have affected not only his appearance but also his ability to move and perform certain tasks. K131’s burial treatment is entirely normative for the period and the wider cemetery context. This could suggest that despite their impairment, this individual was not necessarily marginalised within their social context. However, historical sources account for extensive marginalisation and cruel treatment of the disabled and deformed in this period. So, whilst K131 was buried in a normative manner, it is difficult to reach definitive conclusions regarding how this individual was treated by their contemporaries.