# Age-Related Differences between Old and Very Old Men in Performance and Fatigability Are Evident after Cycling but Not Isometric or Concentric Single-Limb Tasks

Giorgio Varesco, Eric Luneau, Guillaume Y Millet, Léonard Féasson, Thomas Lapole, Vianney Rozand

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## To cite this version:

Giorgio Varesco, Eric Luneau, Guillaume Y Millet, Léonard Féasson, Thomas Lapole, et al. Age-Related Differences between Old and Very Old Men in Performance and Fatigability Are Evident after Cycling but Not Isometric or Concentric Single-Limb Tasks. Medicine and Science in Sports and Exercise, 2023, 55 (9), pp.1641-1650. 10.1249/MSS.0000000000003181. hal-04894552

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# Age-Related Differences between Old and Very Old Men in Performance and Fatigability Are Evident after Cycling but Not Isometric or Concentric Single-Limb Tasks

GIORGIO VARESCO¹, ERIC LUNEAU¹, GUILLAUME Y. MILLET¹,², LÉONARD FÉASSON¹,³, THOMAS LAPOLE¹, and VIANNEY ROZAND¹

¹Université Jean Monnet Saint-Etienne, Lyon 1, Université Savoie Mont-Blanc, Laboratoire Interuniversitaire de Biologie de la Motricité, F-42023, Saint-Etienne, FRANCE; ²Institut Universitaire de France (IUF), FRANCE; and ³Myology Unit, Department of Exercise and Clinical Physiology, University Hospital of Saint-Etienne, FRANCE

## ABSTRACT

VARESCO, G., E. LUNEAU, G. Y. MILLET, L. FÉASSON, T. LAPOLE, and V. ROZAND. Age-Related Differences between Old and Very Old Men in Performance and Fatigability Are Evident after Cycling but Not Isometric or Concentric Single-Limb Tasks. *Med. Sci. Sports Exerc.*, Vol. 55, No. 9, pp. 1641–1650, 2023. **Purpose:** This study aimed to compare performance and fatigability between young (n = 13; 18–30 yr), old (n = 13; 60–80 yr), and very old (n = 12; >80 yr) men during a single-joint isometric (ISO) and concentric (CON) task performed on an isokinetic dynamometer and a cycling (BIKE) task. **Methods:** Participants randomly performed incremental tasks consisting of stages of 75 contractions (i.e., 120 s, 0.8 s on/0.8 s off) for ISO and CON and 120 s at 37.5 rpm (similar duty cycle) for BIKE. Increments were set as a percentage of body weight. Knee extensor maximal force, voluntary activation, and twitch amplitude were measured at baseline, after each stage, and at task failure (five out of eight contractions below the target force or 6 s in a row at a cadence <37.5 rpm). **Results:** Compared with young men, performance (number of stages) was 24% and 40% lower in old and very old men in ISO, 54% and 59% lower in CON, and 36% and 60% lower in BIKE (all *P* < 0.05). Performance of old and very old differed only in BIKE (*P* < 0.01). For the last common stages performed, compared with young, force loss was greater for very old men in ISO and for old and very old men in BIKE (all *P* < 0.05). Overall, for the last common stage performed and task failure, old and very old men presented similar force loss, alterations in voluntary activation, and twitch amplitude. **Conclusions:** Our findings reveal that, with workloads relative to body weight, differences in performance between old and very old men could only be observed during BIKE (i.e., the more ecologically valid task). Results from isometric or concentric conditions might not be transferable to dynamic exercise with large muscle masses. **Key Words:** EXERCISE TESTING, FATIGUE, NEUROMUSCULAR FUNCTION, MUSCLE CONTRACTION, CENTRAL, PERIPHERAL

The inherent deterioration in muscle structure and motor command with advancing age results in a progressive loss of strength, power, and physical function, affecting autonomy and quality of life (1,2). These alterations are exacerbated at very old age (i.e., >80 yr), increasing the risk of frailty, hospitalization, and ultimately death (3). It has been shown that the deterioration in muscle force with age particularly affects the large muscle groups of the lower limbs, such as the knee extensors, whose function affects locomotion and other activities of daily living (4). In addition to the

age-related alteration in force production, the completion of daily activities could be limited by fatigability, defined as an exercise-induced decline in a performance criterion (5) such as the loss in maximal torque or force from a baseline.

The age-related alteration in fatigability depends on the characteristics of the fatiguing task performed, such as the contraction mode (for a review, see [6]), contraction speed (7,8), or the type of workload (9,10). In the literature, the workload is usually set relative to maximal force (or torque) to account for differences in muscle strength between populations. With this approach, we recently observed lower fatigability in old adults compared with young and very old adults after an intermittent incremental isometric task (11). After isokinetic concentric tasks (i.e., standardizing contraction velocity), maximal torque loss is generally greater in old than young adults, with no data available on very old adults (for a review, see [10]). Finally, during cycling tasks, it has been previously shown that maximal force loss was similar between young and old men, but with greater total work for young men (i.e., greater time to task failure) (12). Indeed, the interpretation of

<footnote>Address for Correspondence: Vianney Rozand, Ph.D., Université Jean Monnet, Saint-Etienne, Campus Santé Innovations – IRMIS, 10 rue de la Marandière, 42270 Saint Priest en Jarez, France; E-mail: vianney.rozand@univ-st-etienne.fr.
Submitted for publication September 2022.
Accepted for publication March 2023.</footnote>

<footnote>0195-9131/23/5509-1641/0
MEDICINE & SCIENCE IN SPORTS & EXERCISE®
Copyright © 2023 by the American College of Sports Medicine
DOI: 10.1249/MSS.0000000000003181</footnote>
the age-related differences in fatigability is strongly affected
by absolute performance (e.g., total force–time integral or total
work [11,12]). For instance, when young and old men per-
formed a single-joint concentric and a cycling task at 80% of
their peak power output until task failure, Weavil et al. (12)
observed a greater loss in maximal force for young compared
with old men. However, when young and old men performed
similar total work, the opposite was observed, indicating
greater fatigability in old men.

Although it is important to investigate fatigability at task
failure, it is also important to interpret fatigability at submaxi-
mal levels of exercise after a given exercise duration and/or
workload because task failure is rarely reached during activi-
ties of daily living. Similarly, using workloads that better rep-
resent what is experienced during activities of daily living
would provide further insights into the changes in neuromus-
cular performance with age, as already suggested when study-
ing sex-related differences (13) and cancer-related fatigability
(14). To test participants in more ecologically valid conditions,
the intensity of lower limbs exercise can be set relative to body
weight (14), as most of the activities of daily living involving
the lower limbs, such as walking or climbing stairs, require the
ability to carry our own body weight rather than a percentage
of maximal capacity.

The aim of the present study was to explore performance
and fatigability in young, old, and very old men during and af-
ter single-joint isometric, single-joint concentric, and cycling
fatiguing tasks with workloads set as percentage of body
weight. For all the fatiguing tasks, we hypothesized lower per-
formance with advancing age. We also hypothesized that for
similar task duration, fatigability (maximal force loss) will in-
crease with advancing age. We also expected a concomitant
age-related increase in the RPE because of the higher absolute
workload experienced by the old and very old adults due to
their lower muscle mass over body mass ratio.

METHODS

**Participants.** Thirteen young (<35 yr old), 13 old (60–80 yr old), and 12 very old men (>80 yr old) participated in the study and were clearly informed of the experimental procedures before giving their written informed consent. Participants were free from psychological, musculoskeletal, and neurological disorders or disabilities. Assumption of neuroactive substances, including β-blockers and other drugs influencing heart rate (HR), was considered as exclusion criteria. Participants were asked to avoid exercise and alcohol consumption for 24 h before each visit. Very old men were needed to score at least 24 at the Mini-Mental State Examination (mean ± SD score = 28 ± 3 [15]). All the procedures were approved by the Comité de Protection des Personnes of the University Hospital of Saint-Etienne (sponsor of the study) and were performed in accordance with the Declaration of Helsinki (ClinicalTrials.gov, Identifier: NCT04516538).

**Experimental setting.** For both the isometric (ISO) and the concentric (CON) fatiguing tasks, participants were seated

on an isokinetic dynamometer (Con-Trex MJ; CMV AG,
Dubendorf, Switzerland) and were tested on the right leg.
Hip and knee angles were set at 95° and 90°, respectively
(180° = full extension). The lever arm was measured using
the landmarks present on the dynamometer's arm, represent-
ing the distance between the center of the rotation axis and
the point at which the pad was attached. The center of the
dynamometer rotation axis was aligned with the knee joint
rotation axis. The position of each participant was registered
and kept consistent between sessions. For the cycling task
(BIKE), participants were seated on a validated custom-made
cycle ergometer that allowed to lock the force-measuring pedals
(PF1.0.0, Radlabor GmbH, Freiburg, Germany) (for further
details, see [16]). Torque (ISO and CON) and force (BIKE)
were sampled without filters (16/30-ML880/P; ADInstruments,
Bella Vista, Australia). Pairs of self-adhesive Ag/AgCl surface
electrodes (recording diameter = 10 mm, Kendall MediTrace
130 foam electrode, MA) were placed over the right clavicle
and the tenth left rib, respectively, to measure HR using an octal
bio-amplifier (ML138, AD Instruments) with a bandwidth fre-
quency range of 10–500 Hz and digitized by a Power-Lab Sys-
tem (16/30-ML880/P, AD Instruments). Torque (or force) and
HR signals were recorded simultaneously at 2 kHz on a com-
puter using Labchart v8 (AD Instruments).

**Experimental protocol.** Participants visited the laboratory on four occasions separated by 7 to 10 days. During the first visit, all participants were familiarized with all the experimental procedures, and an accelerometer (wGT3X-BT; ActiGraph, Pensacola, FL) was given to wear for seven consecutive days to assess physical activity (17). The old and very old men also performed a 6-min walk test (6MWT), which consisted in covering the longest distance possible in 6 min on a 30-m corridor (18). Then, they performed a Timed-Up-and-Go (TUG) test, in which participants were required to stand up from a chair, walk a distance of three meters, turn around, and return to the chair (19).

During the successive experimental sessions, participants
performed the incremental tasks (ISO, CON, and BIKE) in a
randomized order. ISO and CON derived from the so-called
quadriceps intermittent fatigue (QIF) test initially developed
in isometric (20) and concentric (21) contraction modes, re-
spectively. In the present study, these tests were adapted to
standardize the duty cycle and duration of the stages across
sessions.

In the first part of each experimental session, participants
performed a standardized isometric warm-up consisting of
three contractions at 30%, 50%, and 70% of the perceived
maximal force. Then, participants performed two maximal
voluntary contractions in both isometric (MVIC; 90°, knee full
extension = 180°) and concentric (MVCC) modes (range of
motion, 60° [90°–150°]; velocity, 120°·s⁻¹). MVCC could
not be performed on the cycle ergometer. An additional trial
was performed if the difference between the peak force values
was >5%.

After 2 min of recovery, two neuromuscular evaluations
(NME) were performed, separated by 1 min of rest. The NME
consisted of a 5-s MVIC during which a single electrical stimulation was superimposed (superimposed twitch [SIT]). Then another stimulation was delivered at rest (twitch [Tw]) ~2 s after the MVIC. Only the NME with the highest MVIC peak force value was kept for further analysis. Visual feedback of the force (or torque) signal and strong verbal encouragement were provided. The fatiguing tasks (ISO, CON, or BIKE) started at least 1 min after the second NME (Fig. 1).

**Fatiguing tasks.** Both ISO and CON consisted of stages of 75 contractions (0.8 s on/0.8 s off; stage duration = 120 s) at increasing workloads until task failure. For ISO, contractions were performed at 90°. For CON, contractions were performed with a range of motion of 60° (90°–150°, knee full extension = 180°) and an angular velocity of 120°·s⁻¹. The workload of the first stage corresponded to 10% of the body weight and was calculated with the following formula:

$$ \text{workload first stage (N·m)} = \frac{[\text{body mass (kg)} \times G] \times \text{lever arm (m)}}{10} $$

where G is the gravitational constant, approximated at 9.80665 m·s⁻². Starting from the second stage, the increments were set at 5% of body weight. For ISO, participants listened to a soundtrack with the contraction–relaxation rhythm. They were instructed to reach the target force as soon as possible after the acoustic signal and maintain the torque level until the next acoustic signal. For CON, participants were instructed to start the contraction immediately after the machine passively returned the leg to the starting position (90°). For CON, peak torque was required to be over the target force, and participants were instructed to limit the torque overshoot. Stages were separated by 1 min. Immediately (~2 s) at the end of each stage and at task failure, NME was performed, and the RPE was scored on a 6–20 Borg scale (22). Verbal encouragement was provided. Task failure was defined as five contractions below the target line over a period of eight contractions. After the last NME at task failure, two MVCC were performed.

BIKE consisted of a bilateral cycling task of 120-s stages at increasing workloads at a cadence of 37.5 rpm (75 pedal strokes). Because of different configurations of the experimental

setting, the workload was calculated differently than ISO and CON. The workload was set at 0.6 W·kg⁻¹ for the first stage and 0.3 W·kg⁻¹ for the successive increments. Participants were provided visual feedback on the cadence and verbal encouragement. Immediately (~2 s) after each stage and at task failure, the pedals were blocked, RPE was scored, and participants performed NME. Task failure was defined when the cadence was below 37.5 rpm for 6 s.

**Peripheral nerve electrical stimulation.** Single-pulse square-wave stimuli of 2-ms duration (400 V) were delivered over the femoral nerve through a constant current stimulator (DS7R; Digitimer, Welwyn Garden City, UK). The cathode electrode (Kendall MediTrace) was placed on the inguinal triangle, and the anode (50 × 90 mm Durastick Plus electrode; DJO Global, Vista, CA) was placed midway between the great trochanter and the lower border of the iliac crest (23). The stimulation intensity was progressively increased by 10 mA until torque or force plateaued. To ensure that all motor axons were spatially activated, this current intensity recorded at plateau was increased by 30%. Mean stimulation intensity was not significantly different across sessions and groups (211 ± 65 mA).

**Data analysis.** All data were analyzed offline using Labchart software (version 8, ADInstruments). Performance was quantified as the total number of stages performed until task failure. In the case of incomplete stage at task failure, the proportion of the last stage was also considered (e.g., 7.5 stages). Torque data obtained during ISO and CON were converted offline from “N·m” to “N” by dividing torque by the lever arm for data analysis. MVIC and MVCC were defined as the peak force reached during the contraction. Fatigability was quantified as the percentage of reduction in MVIC and MVCC (when applicable). Voluntary activation (VA) was calculated using the following equation:

$$ VA(\%) = \left( 1 - \frac{SIT}{Tw} \right) \times 100 $$

where SIT is the amplitude of the superimposed twitch evoked by peripheral nerve stimulation during MVIC, and Tw is the

<figure><img src="image_3.png" /><figcaption>FIGURE 1—Experimental procedures for the three body weight–based QIF tests. Filled arrows indicate single twitch electrical stimulation. Dotted contractions were performed only if the difference between peak force values of the previous contractions was >5%. ISO, isometric body weight–based QIF test; CON, concentric body weight–based QIF test.</figcaption></figure>
amplitude of the twitch evoked at rest. A correction was applied if the stimulation was not delivered at maximal force (24):

$$VA (\%) = 100 - \left[ \frac{SIT \times \left( \frac{\text{Force pre stim}}{\text{MVIC}} \right) \times 100}{\text{Tw}} \right]$$

where Force pre stim is the force level recorded when the SIT was imposed. MVIC, MVCC, and Tw were also expressed relative to body weight (N·kg⁻¹). HR at task failure was calculated as the mean HR over the last 30 s.

**Statistical analysis.** All variables are reported as mean ± SD in the text, tables, and figures. Because force measures from instrumented pedals of the cycle ergometer showed systematically lower values (~30% difference) compared with classic dynamometers (also reported by [16]), data at baseline were analyzed separately for each session. Unpaired *t*-tests were used to analyze differences between old and very old men in the performance at the 6MWT and TUG test. One-way ANOVA was used to analyze age-related differences in participants' characteristics (age, weight, height, physical activity, and workload). One-way ANOVA was also used to analyze for each session separately the age-related differences in neuromuscular data at baseline (absolute and normalized MVIC, MVCC, and Tw; VA), %MVCC loss at task failure (for ISO and CON), and performance (number of contractions). HR at task failure was analyzed using a mixed-effect ANOVA with session as within-group factor and age as between-subject factor. To investigate the effect of age on the evolution of MVIC, Tw, VA, and RPE, generalized estimating equations (GEE) analyses using an autoregressive (AR-1) structure were performed on data expressed relative to baseline (except VA) for each session. Because participants performed different numbers of stages, data were compared until the last stage performed by all participants (i.e., third stage [ISO and BIKE] or second stage [CON]) and then, in a separate analysis, at task failure (25). For all ANOVA and GEE, when significant effects were observed, Bonferroni correction was applied to *post hoc* analyses. Significance was set at *P* ≤ 0.05. For clarity purposes, *post hoc* results for time effects are presented only in the text, whereas only age-related differences are presented in the figures. Because some results could be explained by differences in the load performed relative to MVIC, we ran additional GEE analyses with MVIC as a covariate. Correlation analyses (Pearson) were used to study the relationships between performance and fatigability variables. Statistical analysis was conducted using IBM SPSS (version 23.0; SPSS Inc., Chicago, IL).

## RESULTS

Table 1 summarizes the participants' characteristics. Physical activity was similar across the three age-groups (*P* = 0.209). Old men performed better at the 6MWT (*P* < 0.001) and the TUG test (*P* = 0.001) than very old men.

Three old men and one very old man dropped out of the study. Among them, only one participant (very old man) dropped out of the study because of pain that occurred during

<table><caption>TABLE 1. Characteristics of the participants.</caption><thead><tr><th></th><th>Young (n = 13)</th><th>Old (n = 13)</th><th>Very Old (n = 12)</th></tr></thead><tbody><tr><td>Age (yr)</td><td>24 ± 3</td><td>70 ± 4***</td><td>86 ± 1***†††</td></tr><tr><td>Body mass (kg)</td><td>72.1 ± 8.8</td><td>79.2 ± 9.5</td><td>71.0 ± 5.0</td></tr><tr><td>Height (cm)</td><td>178.0 ± 6.9</td><td>173.8 ± 5.4</td><td>164.7 ± 3.7***†††</td></tr><tr><td>Steps per day</td><td>10,477 ± 2818</td><td>11,647 ± 2399</td><td>9,366 ± 3127</td></tr><tr><td>6MWT (m)</td><td>/</td><td>670 ± 98</td><td>452 ± 92†††</td></tr><tr><td>TUG test (s)</td><td>/</td><td>4.1 ± 0.7</td><td>6.3 ± 1.9††</td></tr></tbody></table>

*Significantly different from young adults.

***P* < 0.01.

****P* < 0.001.

††Significantly different than old adults.

†††*P* < 0.01.

††††*P* < 0.001.

the experimental procedures, whereas the three old men dropped out of the study due to pain that concerned activities not related to the experimental procedures. Thus, 11 old men completed ISO, 10 completed CON, and 13 completed BIKE. For the very old men, 12 completed ISO and BIKE and 11 completed CON.

MVIC, MVCC, and Tw were lower for very old males compared with old males and for old males compared with young males. No differences in VA were observed (ISO: *P* = 0.113; CON: *P* = 0.050; BIKE: *P* = 0.199) (Table 2). Higher values were observed at baseline for old men (mean = 97%, CI = 95%–99%) compared with young (96%, CI = 93%–99%) and very old men (93%, CI = 88%–98%). The increments of 5% of body weight for ISO corresponded to 6% ± 1%, 9% ± 3%, and 12% ± 3% MVIC for young, old, and very old, respectively (age difference, all *P* < 0.05). The increments of 5% of body weight for CON corresponded to 8% ± 1%, 12% ± 4%, and 15% ± 3% MVCC for young, old, and very old, respectively. For CON, young men had lower increments (expressed as % of MVCC) compared with old men (*P* = 0.003) and very old men (*P* < 0.001), with no difference between old and very old men (*P* = 0.084). The relative load reached at task failure for ISO corresponded to 58% ± 15%, 65% ± 9%, and 73% ± 13% of MVIC for young, old, and very old men, respectively. For CON, it corresponded to 61% ± 16%, 49% ± 7%, and 63% ± 17% of MVCC for young, old, and very old men, respectively. For BIKE, power at task failure was 256 ± 51 W (3.6 ± 0.7 W·kg⁻¹), 194 ± 31 W (2.5 ± 0.6 W·kg⁻¹), and 122 ± 19 W (1.7 ± 0.3 W·kg⁻¹) for young, old, and very old men, respectively.

## Performance

Performance showed a significant age-group effect (*P* < 0.001). The number of stages was lower in old and very old men compared with young men for ISO (old: *P* = 0.013; very old: *P* < 0.001), CON, and BIKE (all *P* < 0.001; Fig. 2). For BIKE, a significant difference was also found between old and very old men (*P* = 0.006; Fig. 2). Performance at ISO was correlated with MVIC per body mass for older men (old: *R*² = 0.85, *P* = 0.001; very old: *R*² = 0.68, *P* = 0.016), but not for young men (*R*² = −0.18, *P* = 0.56). Performance at CON was correlated with MVCC per body mass for older men (old: *R*² = 0.70, *P* = 0.036; very old: *R*² = 0.66, *P* = 0.027) not for young men (*R*² = −0.25, *P* = 0.41)
<table><caption>TABLE 2. Neuromuscular properties of the participants at baseline.</caption><thead><tr><th></th><th></th><th>Young (n = 13)</th><th>Old (n = 13)</th><th>Very Old (n = 12)</th></tr></thead><tbody><tr><td rowspan="3">MVIC (N)</td><td>ISO</td><td>627 ± 169</td><td>461 ± 98**</td><td>324 ± 72***†</td></tr><tr><td>CON</td><td>590 ± 124</td><td>440 ± 74**</td><td>306 ± 73***†</td></tr><tr><td>BIKE</td><td>408 ± 89</td><td>295 ± 46***</td><td>212 ± 52***†</td></tr><tr><td rowspan="3">MVIC/body mass (N·kg<sup>-1</sup>)</td><td>ISO</td><td>8.6 ± 1.5</td><td>5.9 ± 1.6***</td><td>4.5 ± 0.9***†</td></tr><tr><td>CON</td><td>8.2 ± 1.1</td><td>5.5 ± 1.0***</td><td>4.3 ± 0.9***†</td></tr><tr><td>BIKE</td><td>5.6 ± 0.8</td><td>3.8 ± 0.9***</td><td>3.0 ± 0.6***†</td></tr><tr><td rowspan="3">MVCC (N)</td><td>ISO</td><td>483 ± 110</td><td>333 ± 61***</td><td>241 ± 49***†</td></tr><tr><td>CON</td><td>485 ± 119</td><td>334 ± 66**</td><td>235 ± 49***†</td></tr><tr><td>BIKE</td><td>6.7 ± 0.9</td><td>3.6 ± 1.8***</td><td>3.4 ± 0.7***</td></tr><tr><td rowspan="3">MVCC/body mass (N·kg<sup>-1</sup>)</td><td>ISO</td><td>6.7 ± 1.1</td><td>3.2 ± 2.0***</td><td>3.0 ± 1.2***</td></tr><tr><td>CON</td><td>176 ± 44</td><td>135 ± 29*</td><td>106 ± 17***</td></tr><tr><td>BIKE</td><td>170 ± 49</td><td>124 ± 26*</td><td>106 ± 17***</td></tr><tr><td rowspan="3">Tw (N)</td><td>ISO</td><td>143 ± 29</td><td>93 ± 25***</td><td>74 ± 18***</td></tr><tr><td>CON</td><td>2.4 ± 0.5</td><td>1.4 ± 0.7***</td><td>1.4 ± 0.5***</td></tr><tr><td>BIKE</td><td>2.3 ± 0.4</td><td>1.2 ± 0.7***</td><td>1.3 ± 0.6***</td></tr><tr><td rowspan="3">Tw/body mass (N·kg<sup>-1</sup>)</td><td>ISO</td><td>2.0 ± 0.3</td><td>1.2 ± 0.4***</td><td>1.0 ± 0.4***</td></tr><tr><td>CON</td><td>95 ± 4</td><td>97 ± 5</td><td>92 ± 7</td></tr><tr><td>BIKE</td><td>96 ± 3</td><td>97 ± 4</td><td>92 ± 7</td></tr><tr><td rowspan="3">VA (%)</td><td>ISO</td><td>95 ± 4</td><td>97 ± 5</td><td>92 ± 7</td></tr><tr><td>CON</td><td>96 ± 3</td><td>97 ± 4</td><td>92 ± 7</td></tr><tr><td>BIKE</td><td>96 ± 4</td><td>97 ± 4</td><td>93 ± 7</td></tr></tbody></table>

*Significantly different from young adults, *P* < 0.05.

** *P* < 0.01.

*** *P* < 0.001.

†Significantly different from old adults, *P* < 0.05.

## Maximal Force

**Common stages performed.** For the common stages performed during ISO, MVIC showed no stage × age-group interaction (*P* = 0.142; Fig. 3A) but age-group (*P* = 0.026) and stage (*P* < 0.001) effects. MVIC dropped from baseline for all common stages (all *P* < 0.05), and MVIC loss was greater only for very old compared with young men (*P* = 0.029).

Older men were not significantly different from young men (*P* = 0.081), with the mean being close to those of very old men for stage 1 (old: 88%, CI = 80%–96%; very old: 89%, CI = 83%–95%), stage 2 (old: 85%, CI = 79%–92%; very old: 86%, CI = 78%–93%), stage 3 (old: 80%, CI = 73%–88%; very old: 80%, CI = 74%–86%). Finally, including the individual MVIC as a covariate in the model, the main effect of age-group was not significant (*P* = 0.156). For CON, significant stage × age-group interaction was found (*P* = 0.025), showing a significant drop in MVIC for all groups across all common stages (all *P* < 0.05; Fig. 3B). For BIKE, significant stage × age-group interaction was found for the common stages performed (*P* < 0.001), showing a significant drop in MVIC for all common stages for old and very old men (all *P* < 0.001) but not for young men (all *P* > 0.05; Fig. 3C).

**At task failure.** MVIC was significantly reduced for the three age-groups and the three sessions (all *P* < 0.001). Significant differences across age-groups at task failure were found in ISO (*P* = 0.023; Fig. 3A) but not in CON (*P* = 0.088) or BIKE (*P* = 0.221), with greater MVIC loss for young compared with very old men (*P* = 0.028).

There was a decrease in MVCC at task failure for ISO (young, −24% ± 11%; old, −23% ± 10%; very old, −22% ± 11%) and

CON (young, −23% ± 16%; old, −21% ± 13%; very old, −26% ± 11%) for the three age-groups (all *P* < 0.01), but no difference between age-groups for both sessions (all *P* > 0.05).

## VA

**Common stages performed.** VA presented a significant stage × age-group interaction for BIKE (*P* = 0.025) but not for the other sessions (all *P* > 0.05; Fig. 3D–F). VA was reduced at stages 2 and 3 for the old men compared with baseline (all *P* < 0.05), but no significant difference between age-groups was observed for all common stages (all *P* > 0.05; Fig. 3F).

**At task failure.** We found no differences from baseline and between age-groups for the three sessions (all *P* > 0.05; Fig. 3D–F).

## Resting Twitch

**Common stages performed.** A significant stage × age-group interaction was found for ISO (*P* < 0.001; Fig. 3G), CON (*P* = 0.001; Fig. 3H), and BIKE (*P* = 0.025; Fig. 3I). During ISO, Tw amplitude was significantly reduced at all common stages for old and very old men, but only at stage 3 for young men (all *P* < 0.05; Fig. 3G).

For CON, Tw amplitude was reduced at all common stages in the three age-groups and was lower for old and very old men compared with young men at stage 3 (all *P* < 0.05; Fig. 3H). For BIKE, Tw amplitude was reduced at all stages for the old men (all *P* < 0.05), but only at stages 2 and 3 for very old men (all *P* < 0.05), whereas no significant changes were observed for the young group (all *P* > 0.05; Fig. 3I).

**At task failure.** Tw amplitude decreased significantly from baseline for the three sessions (all *P* < 0.001) without differences in Tw amplitude loss between age-groups (all *P* > 0.05; Fig. 3G–I).

## Perceived Exertion and HR

For all sessions, RPE showed significant stage × age-group interactions (all *P* < 0.001), increasing significantly from baseline for all sessions in all age-groups (all *P* < 0.001). Old and

<figure><img src="image_4.png" /><figcaption>FIGURE 2—Number of stages performed by the young, old, and very old adults at the isometric (ISO), concentric (CON), and cycling (BIKE) QIF tests (A). \#Significant difference compared with young. $^{*}$Significant difference compared with old. Significance was set as *P* < 0.05.</figcaption></figure>
<figure><img src="image_5.png" /><figcaption>FIGURE 3—Differences between groups in maximal voluntary isometric contraction force (MVIC, *upper row*), VA (*central row*), and twitch amplitude (Tw; *bottom row*) across the isometric (ISO; A, D, G), concentric (CON; B, E, H), and cycling (BIKE; C, F, I) body weight-based QIF tests. The last common stage was stage 3 for ISO and BIKE and stage 2 for CON. \*Significant time–age interaction: significant difference compared with young (*P* < 0.05). \textasciicircled{5}Significant stage × age-group interaction: significant difference compared with old (*P* < 0.05).</figcaption></figure>

very old men presented greater RPE scores compared with young men for all the common stages in ISO, CON, and BIKE, with very old men showing higher scores compared with old men in BIKE at stage 3 (all *P* < 0.05; Fig. 4). At task failure, similar RPE was observed across age-groups for ISO (*P* = 0.081), whereas it was different for CON (*P* = 0.001) and BIKE (*P* < 0.001). We found lower RPE at task failure for old and very old men compared with young men in CON and lower RPE for very old men compared with young men in BIKE (all *P* < 0.05; Fig. 4).

For HR, significant session (*P* < 0.001) and age-group (*P* < 0.001) effects were found, with no significant interaction (*P* = 0.493). For all age-groups, ISO and CON showed significantly lower values compared with BIKE (all *P* < 0.001), without differences between ISO and CON (*P* = 1.000). For the three sessions, young men (ISO, 132 ± 21 bpm; CON, 128 ± 16 bpm; BIKE, 159 ± 21 bpm) showed significantly higher HR at task failure compared with old (ISO, 105 ± 14 bpm; CON, 106 ± 7 bpm; BIKE, 139 ± 17 bpm, *P* = 0.002) and very old men (ISO, 94 ± 15 bpm; CON, 95 ± 23 bpm; BIKE,

<figure><img src="image_6.png" /><figcaption>FIGURE 4—Group differences in the RPE across the isometric (ISO; A), concentric (CON; B), and cycling (BIKE; C) body weight-based QIF test. The last common stage was stage 3 for ISO and BIKE and stage 2 for CON. \*Significant difference compared with young (*P* < 0.05). \textasciicircled{5}Significant difference compared with old (*P* < 0.05).</figcaption></figure>
114 ± 17 bpm; P < 0.001), with higher values for old com-
pared with very old men (P = 0.038).

DISCUSSION

The main findings of the present study were as follows: (i) for a similar task duration (common stages), fatigability (MVIC force loss) was greater for the old and very old men than for young men in BIKE. In ISO, fatigability was greater in very old men compared with the young, whereas it was similar across age-groups for CON. (ii) BIKE was the only session where performance (number of contractions) was lower for very old men compared with old men. (iii) At task failure, fatigability in ISO was greater for young compared with very old men, likely due to the greater number of stages performed by the young adults, whereas it was similar across age-groups for CON and BIKE.

**Functional and neuromuscular characteristics at baseline.** All participants could be defined as active based on their number of steps per day (26). Old men performed better at the 6MWT and TUG test than very old men. Step count was relatively high and similar across age-groups, and participants performed well at the 6MWT and TUG test (27–30). This suggests that, in the present study, the age-related differences in physical function and neuromuscular performance could be primarily due to the effect of aging rather than physical inactivity (31). However, it should be noted that the type or intensity of activity was not evaluated, which could influence the current results regarding age-group-related differences. MVIC and MVCC were lower in the very old group compared with old, and in turn in old compared with young males, with values similar to what has been previously observed on isokinetic dynamometers (32) or cycle ergometer (33). Evoked responses (Tw) were lower in old and very old men compared with young men. This would be mainly due to the loss of muscle mass and fat infiltration within the muscle contractile tissue, reducing maximal force and power output in older adults (34). We did not observe significant differences in the evoked responses between old and very old adults, contrary to Sundberg et al. (32) This discrepancy was probably due to differences in physical activity of the very old group between studies (4590 ± 3606 steps per day in Sundberg et al. [32] vs 9366 ± 3127 steps per day in the present study). Indeed, physical activity has been shown to potentially preserve muscle function and performance, even in very old adults (17,25,35,36). This might also explain the absence of age-related differences in VA, as already suggested by a recent meta-analysis (36).

**Performance (number of contractions).** For all sessions, performance was lower in older men (old and very old) than young men. This was expected because age-related muscle atrophy and structural impairments in the neuromuscular system are known to reduce muscle performance (37,38). Exercising with loads set as percentage of body weight would imply exercising at greater intensity for the groups with altered neuromuscular function, even if the loss of muscle mass might be

limited by the high level of physical activity of our participants.
Interestingly, we did not observe any difference in performance
between old and very old men for ISO and CON, whereas old
men performed better than very old men in BIKE. Specific
mechanisms that could explain these results are listed below.

In ISO, performance was lower for old and very old men compared with young men, in agreement with our first hypothesis. However, there was no significant difference between old and very old men. Previously, we observed greater torque-time integral (absolute performance) for old compared with very old adults after an isometric QIF test (11). The discrepancy in the results is likely due to the choice of the workload (% body weight vs % MVIC). Previously, it was proposed that the slowing in muscle contractile properties with advancing age would lead to lower MU firing rates, resulting in a reduced cost of contraction for the isometric mode (39). This could partially explain the absence of difference in performance, RPE, and MVIC loss between old and very old men, despite the latter exercising at higher percentage of their MVIC.

In CON, old and very old men showed lower performance compared with young men, similarly to ISO. In older men, in addition to the greater workload relative to their MVCC, some evidence suggests that contraction efficiency in concentric mode decreases with advancing age (40,41), associated with greater metabolite accumulation (Pᵢ, H⁺, and dihydrogen phosphate) within the working muscles of old adults (42). However, this would not explain the absence of difference in performance between old and very old men. We speculate that the similar workload (relative to MVCC) between old and very old men, together with the high variability in physiological outcomes (43) and the short duration of exercise, could have masked some of the age-related differences between old and very old men in CON.

For BIKE, performance decreased with advancing age, with very old men showing lower performance compared with old men. The age-related changes in cardiovascular function (in terms of both cardiac output and HR) are well known. Cycling typically involves greater muscle masses, coordination, and cardiovascular stress compared with isokinetic tasks, with the need to increase the delivery of blood to multiple muscles. However, we argue that cardiorespiratory stress was not the main factor limiting performance in BIKE. We believe that the impaired performance across age-groups in BIKE was mainly due to a decrease in cycling gross efficiency with aging (44) and lower exercise tolerance for a similar task performed. The latter is supported by the lower HR values observed with advancing age at task failure and the greater RPE in old and very old men compared with young men. Nevertheless, we cannot rule out the influence of greater cardiorespiratory stress with advancing age in the cycling task.

**Fatigability at similar stages performed.** The present study presents novel results regarding the possible age-related differences in fatigability developed at low versus heavy workloads between young, old, and very old men. For the common stages performed at ISO, unlike what was expected (6), MVIC loss was greater in very old men compared with young men
independent of the stage. MVIC loss for old men was not sig-
nificantly different from the young men, despite the mean
being close to that of very old men. This was probably due
to the slightly lower data dispersion in very old men. Fatigabil-
ity was accompanied by a drop in Tw amplitude starting from
the first stage for old and very old men but not for young men.
These results were most likely due to differences in muscle
composition and the load performed relative to the individual
maximal force production capacity, which corresponded to
~6%, ~9%, and ~12% of MVIC for young, old, and very old
men, respectively. Indeed, adjusting for differences in maxi-
mal force capacity, fatigability was not significantly different
between groups. Surprisingly, even if very old men performed
at a higher relative workload compared with old men, and old
men presented a higher MVIC per unit of body mass than their
very old counterparts, no differences between those two groups
were found for MVIC and Tw amplitude losses or perceived
exertion for all common stages. It is possible that the reduced
cost of contraction for the isometric mode with advancing age
could have counterbalanced impairments in MVIC and Tw for
very old men (39,45). Indeed, performance at ISO correlated
to MVIC for old but not very old men.

For CON, no age-group-related differences in MVIC loss were observed at the two common stages. The limited number of stages performed, in addition to the great between-subject variability in MVIC, could have masked some impairments during CON. Old and very old men showed greater Tw amplitude loss compared with young men at the last common stage. The greater workload increments in old (~12% MVCC) and very old (~15% MVCC) men compared with young men (~8% MVCC) probably induced a faster rise in metabolite accumulation (42). These results were supported by the greater perceived exertion observed for old and very old men compared with young men at all common stages. The lack of differences between old and very old men for CON could be due to the between-subjects variability overcoming a possible age effect for these groups. However, it cannot be excluded that in the concentric fatiguing task, there are no real differences between old and very old in our sample. Indeed, there was a large overlapping for MVCC per body mass at baseline between old and very old men. Further evidence comparing very active individuals is thus required.

For BIKE, MVIC and Tw amplitude losses were greater and occurred earlier in old and very old compared with young men, with the latter group showing similar values to baseline for the four common stages. These results suggest that cycling would better discriminate age-group-related differences at submaximal levels than single-limb fatiguing tasks in either isometric or concentric mode. Similar results were obtained when young and old men were matched for total work during a single-limb concentric versus cycling task (12). It should be noted that the cadence chosen in the present study was very low (37.5 rpm). Because it has been shown that cycling efficiency decreases with age and the difference between young and old adults grows with increasing cadence (44), we could expect even greater age-related differences if faster cadences

were adopted. Other than a reduction in cycling efficiency
(44), the greater workload for each stage relative to peak power
output with aging resulted in a greater RPE for old and very old
men compared with young men. Finally, significant differences
observed in VA across the task could be due to the higher
values observed at baseline for old men compared with young
and very old men. The high level of physical activity in our
sample might have prevented us to observe impairments in VA
previously reported by some authors (for a review, see [36]).

**Fatigability at task failure.** For ISO, differences in MVIC loss were observed only between very old men and young men at task failure, whereas MVCC loss was similar across groups. Previously, our research group found a lower MVIC loss for old compared with young men for a similar force–time integral performed during an isometric QIF test with workloads relative to MVIC. Differences in MVIC loss across age-groups are probably related to differences in performance, and in the present study, performance of old men was lower than that of young men.

For CON, both MVIC and MVCC loss were not different across age-groups at task failure. Similar impairments were observed between old and very old men, which could be explained by differences in contractions efficiency (40,42), maximal shortening velocity (32), and high variability in these physiological outcomes for older adults (43).

Finally, MVIC loss was similar across groups for BIKE at task failure, indicating that the low cadence and exercise intensity induced similar levels of fatigability in the knee extensors for the three age-groups.

Regarding the etiology of fatigability at task failure, the large impairments in contractile function observed after the three fatiguing tasks suggest that peripheral alterations were the main responsible of fatigability for this protocol, as previously reported in aging studies (6,11,12,32). Similar impairments in contractile function at task failure for the three age-groups suggest muscular limiting factors to performance, such as actin-myosin cross-bridge formation, calcium phosphorylation, ATP depletion, or drop in pH (46,47). VA values were not significantly different from baseline, with no differences between age-groups for the three sessions. The use of singlets instead of 100 Hz doublets and the level of physical activity, that might mask some alterations, could partially explain these results. Nevertheless, it is also possible that the rate of metabolites accumulation was not high enough to activate the chemoreceptors of the groups III/IV afferents, which promotes impairments in VA (48,49).

**Limitations.** In the present study, women were not included, preventing us to generalize our results to this population. Considering the paucity of studies investigating the sex-related differences in fatigability in very old adults (11), this should be addressed in future studies. We did not perform maximal sprints to obtain an index of maximal power for BIKE, and thus it was not possible to express power as a percentage of maximal capacity. Contrary to ISO and CON, it was not possible to control for lever arm when setting the workload for BIKE, and we cannot rule out the possibility that different lever
arms influenced our results. Finally, it should be evidenced that our sample of very old men could be the result of the so-called “survival of the fittest” (50). The level of physical activity (steps count) partially supports this hypothesis. The fitness of our sample of very old men could have reduced the differences between old and very old adults usually observed in the literature using isometric or concentric protocols (e.g., [33]).

CONCLUSIONS

The present study showed that, when evaluating the age-related differences between old and very old during and after the single-limb tasks, performance and maximal isometric force loss were not different, resulting in a similar fatigability between old and very old men. Our findings reveal that, with workloads relative to body weight, differences in performance between old and very old men could only be observed during BIKE (i.e., the more ecologically valid task). Results from isometric or concentric conditions

might not be transferable to dynamic exercise with large muscle masses.

The authors thank the dedicated group of participants for their time and effort. The authors also thank Dr. Clément Foschia and Dr. David Hupin for their assistance in participant recruitment, and Dr. Callum G. Brownstein for his assistance in English proofreading.

This research used equipment (Con-Trex MJ; CMV AG, Dubendorf, Switzerland) funded by Saint-Etienne Metropole and Département de la Loire (CPER VITALE).

The authors have no conflicts of interest to declare. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute an endorsement by the American College of Sports Medicine.

G. V., T. L., G. Y. M., L. F., and V. R. conceived and designed the research. G. V., E. L., and V. R. recruited the participants. G. V. and E. L. conducted the experiments and collected the data. G. V. analyzed the data. G. V., T. L., G. Y. M., L. F., and V. R. drafted the manuscript. All authors provided critical appraisal to the manuscript and approved the final version. All authors have read and approved the final version of the manuscript.

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