Residual force enhancement is not altered while force depression is amplified at the cellular level in old age

Abstract

Residual force enhancement (rFE) and residual force depression (rFD) are history-dependent properties of muscle which refer to increased and decreased isometric force following a lengthening or shortening contraction, respectively. The history dependence of force is greater in older than in younger human adults when assessed at the joint level. However, it is unclear whether this amplification of the history dependence of force in old age is owing to cellular mechanisms or is a consequence of age-related remodelling of muscle architecture. Single muscle fibres from the psoas major of old and young F344BN rats were dissected and chemically permeabilized. Single muscle fibres were mounted between a force transducer and length controller, then maximally activated (pCa 4.5). To assess rFD, fibres were actively shortened from 3.1 to 2.5 µm at both a slow (0.15 Lo s-1) and fast (0.6 Lo s-1) speed, with a fixed-end isometric reference contraction at 2.5 µm. To assess rFE, fibres were activated and stretched at 0.3 Lo s-1 from a sarcomere length of 2.2 to 2.5 µm, and 2.7 to 3.0 µm, and compared with fixed-end isometric reference contractions at 2.5 and 3.0 µm, respectively. Isometric force (2.5 µm) was ∼19% lower in muscle fibres from old as compared with young rats (P<0.001). Upon normalizing to fibre cross-sectional area, there was no age-related difference in specific force (P>0.05). rFD was ∼33% greater in muscle fibres from old as compared with young rats (P<0.05), while rFE did not differ between groups (P>0.05). rFD is amplified in old age at the cellular level, while rFE appears to be unchanged; thus, previously reported age-related modification of rFE occurs upstream from the cellular level.

Keywords: Cross-bridge; History dependence of force; Isometric force; Muscle architecture; Single fibre; Stiffness.

Fig. 1.

Representative force traces for residual force depression (rFD) and isometric reference (ISO) conditions. In the rFD protocol, single muscle fibres were passively lengthened to a sarcomere length (SL) of 3.1 µm, activated and shortened to 2.5 µm (i.e. plateau of the force–length relationship) at (A) a slow speed of 0.15 L_o s⁻¹ (where L_o is the optimal length for force production) and (B) an increased speed of 0.6 L_o s⁻¹. Representative force traces of a slow/fast velocity shortening contraction (purple) and isometric reference contraction (black) are shown. An instantaneous stiffness test was performed in both conditions prior to deactivation.

Fig. 2.

Representative force traces for residual force enhancement (rFE) and isometric reference (ISO) conditions. In the rFE protocol, single muscle fibres were (A) set to an average SL of 2.2 µm and passively stretched to 2.5 µm (i.e. plateau of the force–length relationship) at 0.3 L_o s⁻¹ or (B) set to an average SL of 2.7 µm and passively stretched to 3.0 µm (i.e. descending limb of the force–length relationship) at 0.3 L_o s⁻¹. Representative force traces for force enhancement (purple) and isometric reference (black) conditions for a young single fibre are shown.

Fig. 3.

Single muscle fibre cross-sectional area (CSA) and isometric force properties. Absolute force measured at 2.5 µm (n=75 young, n=69 old) (A), cross-sectional area (CSA; n=75 young, n=69 old) (B) and instantaneous stiffness (n=72 young, n=65 old) (C) were lower in single muscle fibres from old as compared with young rats. When force was normalized to CSA, there was no age-related difference in specific force (n=75 young, n=69 old) (D). *Significant difference between young and old (P<0.05).

Fig. 4.

Residual force depression (rFD), stiffness and work of shortening. Absolute (A) and relative (B) rFD (rFD fast: n=49 young, n=40 old; rFD slow: n=48 young, n=42 old), percentage stiffness depression (C) (rFD fast: n=49 young, n=40 old; rFD slow: n=48 young, n=42 old) and work (D) (rFD fast: n=49 young, n=40 old; rFD slow: n=48 young, n=42 old) in young and old fibres when shortening from an average sarcomere length of 3.1 to 2.5 µm at a fast (0.60 L_o s⁻¹) and slow speed (0.15 L_o s⁻¹). Both absolute and relative rFD were greater in the slow than fast condition, and old fibres experienced greater rFD (%) as compared with young fibres. There was a greater reduction in stiffness in the slow speed condition, and old fibres had greater stiffness depression as compared with young fibres. Work was greater during the slow as compared with fast condition, and lower in old as compared with young fibres. *Significant difference between slow and fast with young and old combined (P<0.05). ^‡Significant difference between young and old with slow and fast combined (P<0.05).

Fig. 5.

Linear regression analysis of stiffness depression versus rFD for the slow and fast condition in young and old fibres. (A) Fast condition: young group (purple dotted line, R²=0.78, P<0.05), old group (blue dotted line, R²=0.65, P<0.05). (B) Slow condition: young group (purple dotted line, R²=0.84, P<0.05), old group (blue dotted line, R²=0.59, P<0.05). rFD fast: n=49 young, n=40 old; rFD slow: n=48 young, n=42 old.

Fig. 6.

Residual force enhancement (rFE). Absolute (A) and relative (B) force enhancement on the plateau (short; sarcomere length: 2.5 µm) (n=54 young, n=49 old) and descending limb (long; sarcomere length: 3.0 µm) (n=48 young, n=43 old) of the force–length relationship. rFE was greater at longer as compared with shorter sarcomere lengths, with no age-related differences. *Difference between short and long with young and old combined (P<0.05).