{"doi":"10.1101/2025.08.27.670366","title":"Slow- and fast-contracting skeletal muscle fibers have more similar cellular and molecular contractile function at 37°C than at 25°C in older adults","abstract":"ABSTRACT As human skeletal muscle cellular and molecular contractile properties are temperature-sensitive, the ability to perform experiments at body temperature (∼37°C) may lead to a better understanding of their in vivo responses and potentially their effects upon whole-muscle and whole-body performance. We quantified molecular (myosin-actin cross-bridge mechanics and kinetics) and cellular (specific tension; force divided by cross-sectional area) function in slow-contracting myosin heavy chain (MHC) I and fast-contracting MHC IIA fibers from older adults (n=13, 8 female) at 37°C and compared these to results at 25°C. MHC I fibers were more temperature-sensitive than MHC IIA fibers, showing greater increases in cross-bridge kinetics (MHC I: 4.9-8.7x; IIA: 4x) and number or stiffness of strongly-bound cross-bridges (MHC I: 86%; IIA: 34%), leading to increased specific tension in MHC I (19%), with no change in MHC IIA fibers. The expected relationship between fiber force and size (cross-sectional area, CSA) was stronger at 37°C in both fiber types, explaining 80-82% of the variance compared to 51-52% at 25°C. Specific tension was unchanged with size at 37°C in both fiber types, showing that force increases proportionally with CSA, which may be due to the increased number or stiffness of strongly-bound cross-bridges at this temperature. At 25°C, specific tension decreased with size in agreement with previous experiments. Overall, MHC I and IIA fibers at body temperature (37°C) became more analogous, including similar specific tension and closer cross-bridge kinetics, and force production was more strongly correlated with fiber size compared to a non-physiological temperature. Abstract Figure KEY POINTS SUMMARY Although skeletal muscle function is highly sensitive to temperature, human single fiber studies have only been conducted at ≤30°C. Small-amplitude sinusoidal perturbations were utilized to elucidate mechanisms of single fiber force production at human physiological temperature (37°C). We found that functional differences in slow-contracting myosin heavy chain (MHC I) and fast-contracting MHC IIA fibers observed at 25°C were less apparent at 37°C, as force, crossbridge kinetics, and strongly-bound crossbridges increased more in MHC I fibers than MHC IIA fibers at 37 vs. 25°C. These results indicate that, given the different sensitivity of each fiber type to changes in temperature, functional assessments of muscle should be conducted at 37°C to better translate to vivo conditions.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":558916,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":703544,"name":"Stuart R. Chipkin","orcid":"0000-0003-2114-9480","position":1,"is_corresponding":false},{"id":1001870,"name":"Jane A. Kent","orcid":"0000-0001-5487-2849","position":2,"is_corresponding":false},{"id":449797,"name":"Mark S. Miller","orcid":"0000-0001-8309-8258","position":3,"is_corresponding":false},{"id":1194108,"name":"Brent A. Momb","orcid":"0000-0002-9171-0272","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-19T02:55:30.312295Z","pmid":"40909658","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}