Computational prediction of deformation behavior of TRIP steels under cyclic loading

Mitochondrial dysfunction in aging

Mitochondrial network dynamics may play role in metabolic homeostasis. Whether mitochondrial network dynamics are involved in adaptations to day-night fluctuations in energy supply and demand is unclear. Here we visualized and quantified the mitochondrial network morphology in human skeletal muscle of young healthy lean and older individuals with obesity over the course of 24 h METHODS: Muscle biopsies taken at 5 timepoints over a 24-hour period obtained from young healthy lean and older metabolically impaired obese males were analyzed for mitochondrial network integrity with confocal laser scanning microscopy. Variation of level of fragmentation over the course of the day were aligned with variation of mitochondrial respiration over the day RESULTS: Young healthy lean individuals displayed a day-night rhythmicity in mitochondrial network morphology, which aligned with the day-night rhythmicity of mitochondrial respiratory capacity, with a more fused network coinciding with higher mitochondrial respiratory capacity. In the older individuals with obesity, the mitochondrial network was more fragmented overall compared to young healthy lean individuals and completely lacked 24 h rhythmicity, which was also true for the mitochondrial respiratory capacity CONCLUSIONS: Our data shows a paralleled rhythmicity between mitochondrial network morphology and mitochondrial oxidative capacity, which oscillates over the course of a mimicked real-life day in human skeletal muscle of young, healthy lean individuals. In older individuals with obesity, the lack of a 24-hour rhythmicity in mitochondrial network connectivity was also aligned with a lack in respiratory capacity. This suggests that 24-hour rhythmicity in mitochondrial network connectivity is a determinant of rhythmicity in mitochondrial respiratory capacity. Thus, restoring mitochondrial network integrity may promote mitochondrial respiratory capacity and hence contribute to blunting the metabolic aberrations in individuals with a disturbed 24-hour rhythmicity in metabolism, like older individuals with obesity. 

https://doi.org/10.1016/j.molmet.2023.101727

Twenty-four hour rhythmicity in mitochondrial network connectivity and mitochondrial respiration; a study in human skeletal muscle biopsies of young lean and older individuals with obesity

Exercise to Promote Healthy Mitochondria and Improve Lifestyle of Aging Society

Mitochondrial dynamics is driven by a balance between fusion and fission[1,2]. Fusion connects individual mitochondria to form a network of highly energy-efficient organelle systems. Fission drives fragmentation of the mitochondrial network resulting in less energy-efficient organelles. Nevertheless, fission is critical for the removal of damaged mitochondria and the mitigation of oxidative stress. Well-defined factors that control fusion (mitofusin-1/2, optical atrophy protein-1/2) and fission (dynamin-related protein 1, mitochondrial fusion factor, fission protein 1) regulate mitochondrial connectivity dynamics. Mitochondrial dynamics is critical for energy homeostasis, particularly in the skeletal muscle[1], one of the most plastic organs in adulthood amenable to remodeling by exercise, as well as a sedentary lifestyle and aging[3]. Exercise has long been known to be necessary for healthy aging and energy efficiency, as well as for delaying cardiovascular and metabolic diseases[4]. Exercise benefits are partly mediated by boosting energy metabolism[1]. However, molecular mechanisms of age-related decline in physical fitness, and its counterdelay by exercise, are poorly defined. Skeletal muscle is an excellent organ system for obtaining molecular insights into the interaction between exercise and aging, particularly as it is related to mitochondrial dynamics, muscle quality, and fitness. So far, studies in

/pdf/a-worms-life-ampk-links-muscle-mitochondrial-dynamics-to-1i2qdp6q.pdf

A worm’s life: AMPK links muscle mitochondrial dynamics to physical fitness and healthy aging in Caenorhabditis elegans

Significance Exercise is a powerful anti-aging intervention. In muscle, exercise remodels mitochondrial metabolism and connectiveness, but the role of dynamic mitochondrial remodeling in exercise remains unknown. Using Caenorhabditis elegans, we find that the dynamic cycle of mitochondrial fission–fusion is critical for physical fitness. Exercise induces remodeling of the proteome that depends upon mitochondrial dynamics and delays an aging-associated decline in mitochondrial connectiveness and physical fitness. AMPK, a metabolic regulator that senses low energy availability and controls mitochondrial dynamics, is needed for exercise to maintain physical fitness with age and can recapitulate this exercise benefit. Our data identify the mitochondrial dynamics cycle as an essential mediator of exercise responsiveness and an entry point for interventions to maintain muscle function during aging.

Takafumi Ogawa

Papers

Exercise preserves physical fitness during aging through AMPK and mitochondrial dynamics

Local deformation behavior around ringed notch in trip steel bars under tension