Reduction in Reactive Oxygen Species Production by Mitochondria From Elderly Subjects With Normal and Impaired Glucose Tolerance

Ghosh, Somnath; Lertwattanarak, Raweewan; Lefort, Natalie; Molina-Carrión, Marjorie; Joya-Galeana, Joaquin; Bowen, Benjamin P.; Garduño-García, José de Jesús; Abdul‐Ghani, Muhammad; Richardson, Arlan; Mandarino, Lawrence J.; Remmen, Holly Van; Musi, Nicolas

doi:10.2337/db11-0121

Cited by 114 publications

(127 citation statements)

References 50 publications

(64 reference statements)

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“…Older adults were found to have a decrease in mitochondrial function compared with younger adults (i.e., decreased ATP synthesis); however, older adults with normal glucose tolerance had similar ATP production level compared with older adults with impaired glucose tolerance (44). On the other hand, exercise reverses age-related declines in mitochondrial oxidative capacity and ATP production, which may be part of the underlying mechanism through which exercise improves insulin sensitivity (44,45).…”

Section: Effects Of Agingmentioning

confidence: 99%

The Pathophysiology of Hyperglycemia in Older Adults: Clinical Considerations

2017

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Nearly a quarter of older adults in the U.S. have type 2 diabetes, and this population is continuing to increase with the aging of the population. Older adults are at high risk for the development of type 2 diabetes due to the combined effects of genetic, lifestyle, and aging influences. The usual defects contributing to type 2 diabetes are further complicated by the natural physiological changes associated with aging as well as the comorbidities and functional impairments that are often present in older people. This paper reviews the pathophysiology of type 2 diabetes among older adults and the implications for hyperglycemia management in this population.Diabetes is one of the leading chronic medical conditions among older adults, with high risk for vascular comorbidities such as coronary artery disease, physical and cognitive function impairment, and mortality. Despite decades of effort to prevent diabetes, diabetes remains an epidemic condition with particularly high morbidity affecting older adults. In fact, nearly 11 million people in the U.S. aged 65 years or older (more than 26% of adults aged 65 years or older) meet current American Diabetes Association criteria for diabetes (diagnosed and undiagnosed), accounting for more than 37% of the adult population with diabetes (1). At the same time, adults 65 years or older are developing diabetes at a rate nearly three-times higher than younger adults: 11.5 per 1,000 people compared with 3.6 per 1,000 people among adults aged 20-44 years old (1). However, increasing research in diabetes and aging has improved our understanding of the pathophysiology of diabetes and its association with aging and led to the development of a number of antihyperglycemic medications. The mechanism of diabetes complications has been previously reviewed (2). The current paper reviews the pathophysiology of type 2 diabetes among older adults and the implications for hyperglycemia management in this population. PATHOPHYSIOLOGY OF TYPE 2 DIABETESType 2 diabetes is by far the most prevalent form of diabetes in older adults and is an age-related disorder. The criteria for diagnosing diabetes are the same for all age groups because the risks of diabetes-related complications are associated with hyperglycemia over time across all age groups (3). Older adults are at high risk for the development of type 2 diabetes due to the combined effects of genetic, lifestyle, and aging influences. These factors contribute to hyperglycemia through effects on both b-cell insulin secretory capacity and on tissue sensitivity to insulin. The occurrence of type 2 diabetes in an older person is complicated by the comorbidities and functional impairments associated with aging.Hyperglycemia develops in type 2 diabetes when there is an imbalance of glucose production (i.e., hepatic glucose production during fasting) and glucose intake (i.e.,

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Section: Effects Of Agingmentioning

confidence: 99%

The Pathophysiology of Hyperglycemia in Older Adults: Clinical Considerations

2017

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“…PGC-1␣ mRNA and protein content are reduced in both slow-and fast-twitch muscles with age (21, 30,45, 82,147), suggesting that reductions in mitochondrial function or content could be attributable to the loss of this coactivator. Lessons from PGC-1␣ transgenic and knockout animals have been instrumental in the understanding of the role that this coactivator plays in mitochondrial biogenesis and aging.…”

Section: Pgc-1␣ and Agingmentioning

confidence: 99%

“…sarcopenia. Additionally, a limited number of the studies that have performed transcriptomic and proteomic assessments in young and aged muscle (Tables 1 and 2) have considered physical activity levels when making comparisons between age groups (44,45,97,111,(167)(168)(169). Thus future work should attempt to match subjects for physical activity to tease apart the effect of aging per se from the consequences of physical inactivity on the transcriptome and the proteome.…”

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confidence: 99%

Mitochondria, Muscle Health, and Exercise with Advancing Age

2015

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Skeletal muscle health is dependent on the optimal function of its mitochondria. With advancing age, decrements in numerous mitochondrial variables are evident in muscle. Part of this decline is due to reduced physical activity, whereas the remainder appears to be attributed to age-related alterations in mitochondrial synthesis and degradation. Exercise is an important strategy to stimulate mitochondrial adaptations in older individuals to foster improvements in muscle function and quality of life.Heather N. Carter, Chris C. W. The process of aging exploits the malleable nature of skeletal muscle. The age-related loss of muscle mass was termed sarcopenia, based on the Greek (sarx, flesh) and (penia, poverty) in 1988 (139). Accompanying this loss are profound architectural and molecular changes that alter muscle quality and are manifested in functional limitations. Decreases in muscle fiber number as well as fiber cross-sectional area are both contributing factors to sarcopenia (92) and consequently adversely affect force production (strength) (46, 63) and endurance of the older individual (12). Muscle mass typically peaks in the mid-20s (12, 34,92), and thereafter several distinct phases of muscle loss have been identified. In the third to fifth decade of life, a slow rate of muscle mass loss is noted, amounting to ϳ10% in total (34,92). In later adulthood (Ͼ45 yr), the rate of muscle loss increases, with appraisals ranging between 0.5 and 1.4% per year (12, 34,69). Even more dramatic changes are noted beyond the sixth decade of life. Along with the functional impairments imposed by sarcopenia, are the associated escalations in health care costs, along with coincident rises in metabolic diseases (e.g., Type 2 diabetes, obesity) and a greater risk of falls (67). In the U.S., it is expected that those 65 years of age and over will comprise ϳ20% of the population, or ϳ72 million people, by the year 2030 (20). Since the proportion of older adults is increasing, continued research into the mechanisms of muscle loss is warranted, along with the investigation of therapeutic strategies that can mitigate muscle atrophy during aging. Mitochondria have been implicated as potential mediators of sarcopenia. Recently, it has been suggested that dysfunction of these organelles can be considered a feature of aging (105). However, considerable controversy exists regarding the extent to which muscle mitochondria may be dysfunctional with aging, and thereby contribute to the loss of this tissue. Thus the purpose of this review is to examine the literature with respect to mitochondrial content and function in muscle with advancing age, and provide a perspective on the effectiveness of endurance/aerobic exercise as an intervention for mitochondrial biogenesis and muscle homeostasis in older individuals. Structural Features of Muscle Relevant to SarcopeniaIn young, healthy individuals, skeletal muscle comprises ϳ40% of total body mass and is important for locomotion and whole body metabolism. Myosin ATPase histochemistry and electrop...

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“…In addition, PGC‐1α extends health span and life span of a mouse model of premature aging arising from mitochondria defects (Sahin et al., 2011). Importantly, in line with the mitochondrial decline, PGC‐1α expression decreases during muscle aging in different species, including humans (Ghosh et al., 2011; Kang, Chung, Diffee, & Ji, 2013; Short et al., 2005; Vina et al., 2009). Moreover, PGC‐1α improves various muscle disorders, for example, denervation‐induced fiber atrophy (Sandri et al., 2006) or Duchenne muscular dystrophy (Handschin, Kobayashi et al., 2007).…”

Section: Introductionmentioning

confidence: 99%

PGC‐1α affects aging‐related changes in muscle and motor function by modulating specific exercise‐mediated changes in old mice

et al. 2017

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SummaryThe age‐related impairment in muscle function results in a drastic decline in motor coordination and mobility in elderly individuals. Regular physical activity is the only efficient intervention to prevent and treat this age‐associated degeneration. However, the mechanisms that underlie the therapeutic effect of exercise in this context remain unclear. We assessed whether endurance exercise training in old age is sufficient to affect muscle and motor function. Moreover, as muscle peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α) is a key regulatory hub in endurance exercise adaptation with decreased expression in old muscle, we studied the involvement of PGC‐1α in the therapeutic effect of exercise in aging. Intriguingly, PGC‐1α muscle‐specific knockout and overexpression, respectively, precipitated and alleviated specific aspects of aging‐related deterioration of muscle function in old mice, while other muscle dysfunctions remained unchanged upon PGC‐1α modulation. Surprisingly, we discovered that muscle PGC‐1α was not only involved in improving muscle endurance and mitochondrial remodeling, but also phenocopied endurance exercise training in advanced age by contributing to maintaining balance and motor coordination in old animals. Our data therefore suggest that the benefits of exercise, even when performed at old age, extend beyond skeletal muscle and are at least in part mediated by PGC‐1α.

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Reduction in Reactive Oxygen Species Production by Mitochondria From Elderly Subjects With Normal and Impaired Glucose Tolerance

Cited by 114 publications

References 50 publications

The Pathophysiology of Hyperglycemia in Older Adults: Clinical Considerations

The Pathophysiology of Hyperglycemia in Older Adults: Clinical Considerations

Mitochondria, Muscle Health, and Exercise with Advancing Age

PGC‐1α affects aging‐related changes in muscle and motor function by modulating specific exercise‐mediated changes in old mice

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