Aging‐associated Abnormalities of Diaphragm Contractile Function in Wistar‐Kyoto Rats
Bibliographic record
Abstract
Aging presents a decline of respiratory function and is a significant contributor to aging‐associated morbidity and mortality. Specifically, reduced diaphragm muscle function can impair inspiratory force, promote insufficient ventilation during increased physical demand, and contribute to poor airway clearance. Rodent models of aging provide a means to directly assess and characterize abnormalities in diaphragm function; however, rodent models of aging can also possess concomitant pathological states, which should not be disregarded. The Wistar‐Kyoto rat (WKY) can exhibit modifications in cardiovascular function with advanced age. Both cardiovascular and respiratory functions are linked, and can deteriorate over a lifespan. Thus, we used a comprehensive evaluation of cardiac and respiratory function to investigate age‐related abnormalities of hemodynamic and respiratory muscle function. Diaphragm strips from young (~0.4yrs; n= 7, 14 strips) and aged (~2.3yrs; n=8, 14 strips) male WKY were used to investigate in vitro diaphragm force‐frequency (1–120Hz) relationship, fatigue and recovery. Aged diaphragm demonstrated ~30% decrease in force production at lower ranges of stimulation frequencies (i.e., 1–40Hz), compared to young diaphragm. Peak rate of force production (dT/dtmax, index of contractility) was also reduced by up to ~37% (p<0.05) at lower stimulation frequencies, compared to young diaphragm. In response to fatiguing stimulation, young and aged diaphragm force was equivalently reduced. While both aged and young diaphragm recovered to the same level of force, aged diaphragm recovered to it's maximal force ~30% faster than young diaphragm, where increases in force (normalized to maximal force) were up to 10% greater in aged diaphragm over time (p<0.05). In effort to investigate whether changes in force‐frequency relationship between adult and aged rats was specific to respiratory muscle, we also investigated the contractile properties of soleus (predominantly type I; slow‐twitch) and extensor digitorum longus (EDL; predominantly type IIb; fast‐twitch) muscles. Aged soleus demonstrated ~50% reduction in force production over 20–90Hz stimulation frequencies, compared to young soleus (p<0.05). In contrast, force‐frequency curves were similar between young and aged EDL. Herein, these findings demonstrate a right‐ward shift in the force‐frequency curve generated by aged diaphragm, accompanied by impaired rate of force production at lower stimulus frequencies. Maximal force production was conserved between young and aged diaphragm, thus mechanistic impairments of aged diaphragm are likely attributable to augmented calcium release, prior to the onset of deficits in myofilament function with aging. Support or Funding Information CIHR and NSERC
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".