Effects of aging and exercise training on mitochondrial function and apoptosis in the rat heart

No, Mi‐Hyun; Heo, Jun‐Won; Yoo, Su-Zi; Kim, Chang‐Ju; Park, Dong‐Ho; Kang, Ju‐Hee; Seo, Dae Yun; Han, Jin; Kwak, Hyo‐Bum

doi:10.1007/s00424-020-02357-6

Cited by 42 publications

(30 citation statements)

References 69 publications

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“…It has been shown that cardiac mitochondrial oxygen consumption decreases significantly with increasing age. 45 Interestingly, we observed that the mitochondria in aged adult Ahnak1‐KO cardiomyocytes are able to overcome the decrease in oxygen consumption, as demonstrated by significantly increased mitochondrial maximal respiratory and maximal reserve respiratory capacity compared with those of aged adult WT cardiomyocytes. The direct effect of Ahnak1 on mitochondrial oxidative capacity was substantiated in AC16 cells.…”

Section: Discussionmentioning

confidence: 74%

“… 48 It has been demonstrated that the age‐related reduction of oxygen consumption is a consequence of reduced functional activity of the OXPHOS system. 45 , 49 Previous human and animal studies on gene and protein expression revealed significant down‐regulation of mitochondrial respiratory chain complexes in aging skeletal muscle and heart, particularly in interfibrillar mitochondria. 12 , 14 , 27 , 45 , 50 Interestingly, we observed in our study that suppression of the Ahnak1 gene in aged adult heart and TA muscles results in up‐regulation of complexes cIII and cV expression compared with aged adult WT mice.…”

Section: Discussionmentioning

confidence: 99%

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Age‐related decline in murine heart and skeletal muscle performance is attenuated by reduced Ahnak1 expression

Mahmoodzadeh

Koch

Schriever

et al. 2021

J cachexia sarcopenia muscle

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Background Aging is associated with a progressive reduction in cellular function leading to poor health and loss of physical performance. Mitochondrial dysfunction is one of the hallmarks of aging; hence, interventions targeting mitochondrial dysfunction have the potential to provide preventive and therapeutic benefits to elderly individuals. Meta-analyses of age-related gene expression profiles showed that the expression of Ahnak1, a protein regulating several signal-transduction pathways including metabolic homeostasis, is increased with age, which is associated with low VO 2MAX and poor muscle fitness. However, the role of Ahnak1 in the aging process remained unknown. Here, we investigated the age-related role of Ahnak1 in murine exercise capacity, mitochondrial function, and contractile function of cardiac and skeletal muscles. Methods We employed 15-to 16-month-old female and male Ahnak1-knockout (Ahnak1-KO) and wild-type (WT) mice and performed morphometric, biochemical, and bioenergetics assays to evaluate the effects of Ahnak1 on exercise capacity and mitochondrial morphology and function in cardiomyocytes and tibialis anterior (TA) muscle. A human left ventricular (LV) cardiomyocyte cell line (AC16) was used to investigate the direct role of Ahnak1 in cardiomyocytes. ResultsWe found that the level of Ahnak1 protein is significantly up-regulated with age in the murine LV (1.9-fold) and TA (1.8-fold) tissues. The suppression of Ahnak1 was associated with improved exercise tolerance, as all aged adult Ahnak1-KO mice (100%) successfully completed the running programme, whereas approximately 31% male and 8% female WT mice could maintain the required running speed and distance. Transmission electron microscopic studies showed that LV and TA tissue specimens of aged adult Ahnak1-KO of both sexes have significantly more enlarged/elongated mitochondria and less small mitochondria compared with WT littermates (P < 0.01 and P < 0.001, respectively) at basal level. Further, we observed a shift in mitochondrial fission/fusion balance towards fusion in cardiomyocytes and TA muscle from aged adult Ahnak1-KO mice. The maximal and reserve respiratory capacities were significantly higher in cardiomyocytes from aged adult Ahnak1-KO mice compared with the WT counterparts (P < 0.05 and P < 0.01, respectively). Cardiomyocyte contractility and fatigue resistance of TA muscles were significantly increased in Ahnak1-KO mice of both sexes, compared with the WT groups. In vitro studies using AC16 cells have confirmed that the alteration of mitochondrial function is indeed a direct effect of Ahnak1. Finally, we presented Ahnak1 as a novel cardiac mitochondrial membrane-associated protein.Conclusions Our data suggest that Ahnak1 is involved in age-related cardiac and skeletal muscle dysfunction and could therefore serve as a promising therapeutical target.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Age‐related decline in murine heart and skeletal muscle performance is attenuated by reduced Ahnak1 expression

Mahmoodzadeh

Koch

Schriever

et al. 2021

J cachexia sarcopenia muscle

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“…Therefore, cardiomyocytes are more susceptible to mitochondrial dysfunction than any other cells. Mitochondrial ROS production increases gradually in cardiomyocytes during cardiac aging, accompanied by significantly weakened respiratory function and Ca 2+ retention, which lead to cardiomyocyte injury and functional loss [41]. Mitochondrial dysfunction increases cardiac aging-related protein expression and apoptosis-inducing factor-(AIF-) associated cardiomyocyte apoptosis and exacerbates cardiac remodeling in aging mice [42].…”

Section: Oxidative Stressmentioning

confidence: 99%

Cardiac Aging: From Basic Research to Therapeutics

Yan

Sun

et al. 2021

Oxidative Medicine and Cellular Longevity

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With research progress on longevity, we have gradually recognized that cardiac aging causes changes in heart structure and function, including progressive myocardial remodeling, left ventricular hypertrophy, and decreases in systolic and diastolic function. Elucidating the regulatory mechanisms of cardiac aging is a great challenge for biologists and physicians worldwide. In this review, we discuss several key molecular mechanisms of cardiac aging and possible prevention and treatment methods developed in recent years. Insights into the process and mechanism of cardiac aging are necessary to protect against age-related diseases, extend lifespan, and reduce the increasing burden of cardiovascular disease in elderly individuals. We believe that research on cardiac aging is entering a new era of unique significance for the progress of clinical medicine and social welfare.

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“…Exercise does not reverse the natural consequences of aging, but it does slow down systemic and cellular injuries [21]. Aerobic exercise has been the most studied form of exercise during aging [23][24][25][26]. However, the most significant prevention of neuromuscular degeneration (i. e., sarcopenia and loss of strength) associated with aging occurs as a result of resistance training (RT).…”

Section: Biomarkers and Redox Balance In Aging Rats After Dynamic Andmentioning

confidence: 99%

Biomarkers and Redox Balance in Aging Rats after Dynamic and Isometric Resistance Training

et al. 2020

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Aging muscle is prone to sarcopenia and its associated telomere shortening and increased oxidative stress. Telomeres are protected by a shelterin protein complex, proteins expressed in response to DNA damage. Aerobic exercise training has shown to positively modulate these proteins while aging, but the effects of resistance training are less clear. This investigation was to examine the role of dynamic and isometric RT on markers of senescence and muscle apoptosis: checkpoint kinase 2, 53 kDa protein, shelterin telomere repeat binding 1 and 2, DNA repair, telomere length and redox state in the quadriceps muscle. Fifteen 49-week-old male rats were divided into three groups: control, dynamic resistance training, and isometric resistance training. Dynamic and isometric groups completed five sessions per week during 16 weeks at low to moderate intensity (20–70% maximal load). Only dynamic group decreased expression of 53 kDa protein, proteins from shelterin complex, oxidative stress, and improved antioxidant defense. There was no difference among groups regarding telomere length. In conclusion, dynamic resistance training was more effective than isometric in reducing markers of aging and muscle apoptosis in elderly rats. This modality should be considered as valuable tool do counteract the deleterious effects of aging.

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Effects of aging and exercise training on mitochondrial function and apoptosis in the rat heart

Cited by 42 publications

References 69 publications

Age‐related decline in murine heart and skeletal muscle performance is attenuated by reduced Ahnak1 expression

Age‐related decline in murine heart and skeletal muscle performance is attenuated by reduced Ahnak1 expression

Cardiac Aging: From Basic Research to Therapeutics

Biomarkers and Redox Balance in Aging Rats after Dynamic and Isometric Resistance Training

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