scholarly journals Late‐in‐life treadmill training rejuvenates autophagy, protein aggregate clearance, and function in mouse hearts

Aging Cell ◽  
2021 ◽  
Author(s):  
Jae Min Cho ◽  
Seul‐Ki Park ◽  
Rajeshwary Ghosh ◽  
Kellsey Ly ◽  
Caroline Ramous ◽  
...  
2011 ◽  
Vol 53 (8) ◽  
pp. 742-750 ◽  
Author(s):  
THERESE E JOHNSTON ◽  
KYLE E WATSON ◽  
SANDY A ROSS ◽  
PHILIP E GATES ◽  
JOHN P GAUGHAN ◽  
...  

2020 ◽  
Author(s):  
Madhuja Samaddar ◽  
Jérôme Goudeau ◽  
Melissa Sanchez ◽  
David H. Hall ◽  
K. Adam Bohnert ◽  
...  

AbstractSomatic cells age and die, but the germ-cell lineage is immortal. In C. elegans, oocyte-maturation signals from sperm trigger the clearance of carbonylated proteins and protein aggregates. Here, we explore the cell biology of this proteostasis renewal in the context of a whole-genome RNAi screen for knockdowns that interfere with aggregate clearance. Oocyte-maturation signals are known to trigger protein-aggregate removal via lysosome acidification, and our findings suggest that lysosomes are acidified as a consequence of changes in ER morphology and function that permit assembly of the lysosomal V-ATPase. Once lysosomes are acidified, our genetic findings support the model that they remove aggregates by microautophagy. We also define two functions for mitochondria in this proteostasis renewal, both of which appear to be independent of mitochondrial ATP generation. Finally, many genes from the screen also regulate lysosome acidification and age-dependent protein aggregation in the soma, suggesting a fundamental mechanistic link between proteostasis renewal in the germline and the maintenance of the soma.


2015 ◽  
Vol 47 ◽  
pp. 359
Author(s):  
Kimberly Smith ◽  
Kurt Jackson ◽  
Kimberly Bigelow ◽  
Lloyd Laubach ◽  
Aimee Carpenter ◽  
...  

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Celine Baligand ◽  
Yi-Wen Chen ◽  
Fan Ye ◽  
Sachchida Nand Pandey ◽  
San-Huei Lai ◽  
...  

The genetic and molecular events associated with changes in muscle mass and function after SCI and after the implementation of candidate therapeutic approaches are still not completely known. The overall objective of this study was to identify key molecular pathways activated with muscle remodeling after SCI and locomotor training. We implemented treadmill training in a well-characterized rat model of moderate SCI and performed genome wide expression profiling on soleus muscles at multiple time points: 3, 8, and 14 days after SCI. We found that the activity of the protein ubiquitination and mitochondrial function related pathways was altered with SCI and corrected with treadmill training. The BMP pathway was differentially activated with early treadmill training as shown by Ingenuity Pathway Analysis. The expression of several muscle mass regulators was modulated by treadmill training, includingFst,Jun,Bmpr2,Actr2b, andSmad3. In addition, key players in fatty acids metabolism (LplandFabp3) responded to both SCI induced inactivity and reloading with training. The decrease inSmad3andFstearly after the initiation of treadmill training was confirmed by RT-PCR. Our data suggest that TGFβ/Smad3 signaling may be mainly involved in the decrease in muscle mass observed with SCI, while the BMP pathway was activated with treadmill training.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Matthew J. Peterson ◽  
Nanyamka Williams ◽  
Kevin Caves ◽  
Miriam C. Morey

Background. Partial unweighted treadmill training is a potentially effective modality for improving fitness and function in frail elders. We tested the feasibility of partial unweighted treadmill training in older, mobility-impaired veterans.Methods. Eight mobility-impaired elders participated in partial unweighted treadmill training three times/week for twelve weeks. Outcome measures included gait speed, performance-oriented mobility assessment (POMA), eight foot up and go, and the SF-36 physical functioning short form.Results. There was significant improvement in treadmill walking time (+8.5 minutes;P<0.001), treadmill walking speed (+0.14 meters/second;P=0.02), and percent of body weight support (−2.2%;P=0.02). Changes in physical performance included usual gait speed (+0.12 meters/second;P=0.001), rapid gait speed (+0.13 meters/second;P=0.01), POMA (+2.4 summary score;P<0.001), and eight foot up and go (−1.2 seconds;P=0.05).Conclusions. Partial unweighted treadmill training is feasible in mobility-impaired elders. Improvements in treadmill training capacity resulted in clinically meaningful improvements in fitness levels and improved mobility.


2021 ◽  
Author(s):  
Jae Min Cho ◽  
Kellsey Ly ◽  
Caroline Ramous ◽  
Lauren Thompson ◽  
Michele Hansen ◽  
...  

There is evidence for a progressive decline of protein quality control mechanisms during the process of cardiac aging. This enables the accumulation of protein aggregates and damaged organelles that contribute to age-associated cardiac dysfunction. Macroautophagy (referred to as autophagy) is the process by which post-mitotic cells such as cardiomyocytes clear defective proteins and organelles. We hypothesized that late-in-life exercise training improves autophagy, protein aggregate clearance, and function that is otherwise dysregulated in hearts from old vs adult mice. As expected, 24-month old male C57BL/6J mice (old) exhibited : (i) repressed autophagosome formation and protein aggregate accumulation in the heart; (ii) systolic and diastolic dysfunction; and (iii) reduced exercise capacity, vs. 8-month old (adult) mice (all p< .05). Separate cohorts of 21 month old mice completed a 3-month progressive resistance treadmill-running program (old-ETR) that improved (all < .05) : (i) body composition; (ii) exercise capacity; and (iii) soleus muscle citrate synthase activity, vs. age-matched mice that did not train (old-SED). Importantly, (iv) protein expression of autophagy markers indicated trafficking of the autophagosome to the lysosome increased, (v) protein aggregate clearance improved, and (vi) overall function was enhanced (all p<0.05), in hearts from old-ETR vs. old-SED mice. Dietary maneuvers and pharmacological interventions shown to elevate basal autophagy are reported to mitigate / reverse age-associated cardiac dysfunction. Here we show the first evidence that a physiological intervention initiated late-in-life improves autophagic flux, protein aggregate clearance, and overall function in mouse hearts.


Author(s):  
M. Boublik ◽  
W. Hellmann ◽  
F. Jenkins

The present knowledge of the three-dimensional structure of ribosomes is far too limited to enable a complete understanding of the various roles which ribosomes play in protein biosynthesis. The spatial arrangement of proteins and ribonuclec acids in ribosomes can be analysed in many ways. Determination of binding sites for individual proteins on ribonuclec acid and locations of the mutual positions of proteins on the ribosome using labeling with fluorescent dyes, cross-linking reagents, neutron-diffraction or antibodies against ribosomal proteins seem to be most successful approaches. Structure and function of ribosomes can be correlated be depleting the complete ribosomes of some proteins to the functionally inactive core and by subsequent partial reconstitution in order to regain active ribosomal particles.


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