Effectiveness of iso-inertial resistance training on eccentric and concentric power, physical performance, and risk of falls in physically active middle-older adults: a randomised controlled trial

Objective : To evaluat e the effectivene ss of iso-iner tial resist ance tr aining on eccent ric pow e r compared t o gravita tional t raining in phy sically active middle-older adul ts.

Parallel-group, randomis ed controll ed trial a t Espai Esport Wellness Cente r (Granoll ers , Spain). Forty-four physically active adults (>57 years of age) were randomised to i so-inertial (n=21) or gravita tional (n=23) tr aining groups ( R software; 1 :1 ra tio). Particip ants had to complet e a 6- week trai ning progr am (2 sessions/week) consisting of thr ee e xe rcises (forward l unge, side l unge , forward lunge with row). Primary outcome: power in the eccen tric phase of each exercis e evaluat ed with both iso-inerti al and gravitatio nal devices. Second ary outcomes: c oncentric powe r, physical performance, risk of falls. Only outcome evalua tors wer e blinded. We used multivariat e linear r egression mod els to analyse the e ffect of interventi ons.

Iso-in erti al tr aining showed b et ter eccent ric power gains than gr avitati onal tr aining fo r iso-inertial syst em evalua tion, al though t he difference was only st atis tically significant for th e side lunge. Fo rward lunge : be tween-gro up difference 3.99 W (95% CI: -3.99 t o 11 .33, p: 0 .28); side lunge: difference 8.50 W (95% CI: 2.13 to 14.87; p: 0.01); forward lunge with row: difference 14.07 W (95% CI: -2.07 -to 30.20, p: 0.09). We observed no differenc es for the gravitation al system evaluation no r for concentric power , physical performance, and risk of falls. The two groups improved remarka bly from baseline for a ll outcomes. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

Iso-inertial resis tance trai ning might lead to be tt er eccent ric p ower gains th an gravitation al t raining. Both appr oaches s eem equ ally effective in impr oving concentric p ower an d physical performance, a nd reducing th e r isk of falls. Trial registration: ClinicalTrials.gov (NC T 06160089).

Middle-olde r adults, iso-i nerti al traini ng, resista nce trai ning, strength training , eccentric powe r, flywheel WHAT IS ALREA DY KNO WN ON T HIS TO PIC - Physical exercis e in middle-olde r a dults is an effective s tra tegy to p romot e h e alth and improve quality of life. - Resistance tra ining using iso-iner tial d evices genera tes a n advant age in hyp ertr ophy, electr omyographic activity o r balanc e compared to cable-r esista nce t raining in middle- older adul ts. - The power a t which an action is p er formed is co nsider ed a pr edict or of functiona l capacity, as it is associat ed with th e ex e cution of activiti es of daily living such as climbing stairs, ge tting up from a chair or walking. WHAT T HIS STUDY AD DS - The iso-inerti al tr aining system improve s muscle power in th e eccent ric phase c ompare d to th e gravita tional system, a lthough th e difference is only sta tistically significant for th e side lunge ex ercise . - Iso-iner tial an d gravit ation al r esistanc e tr aining a re equally effective in i mproving concentric powe r, and physical pe rforma nce and reducing th e risk of falls. - Using iso´-inertial devices is recommen ded to evalua te powe r in the eccen tric phase, as they may capture b et ter the ecce ntric d e mands than gravita tion al devices. HOW T HIS STUDY M IGHT AFFEC T RESEARCH, P RACT ICE OR POLICY - Using iso-inertial devices for r esistance t raining in middle-old er adul ts seems a p romising way to improve the powe r in the eccent r ic phase of an action. - Improving eccent ric powe r in old er a dults is crucial d ue to its tra nsfer t o daily life activities. - Regardless of the tr aining system, clinici ans should prescr ibe resist ance tr aining programs to middle-olde r adul ts as thes e prog rams remarkably incr ease powe r and physical performance a nd reduc e the risk of falls. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint

Background and objectives With the popula tion 's pr ogressive incr e ase in life e xpect ancy, a tt ention t o agei ng has a ttr acte d increased int eres t in rece nt ye ars. Act ions promo ting he althy ageing ar e ke y to slowing t h e physiological progressive l oss of skele tal muscle mass and functio n as a perso n a ges. In p ar ticular , muscle strengt h and pow er ar e r educe d during aging, harming old er a dults’ f unctional cap acity and quali ty of life (1–3) . R ecen t r esearc h has r evealed a significant d ecre ase in muscle streng th of 1.5-5% each year from age 50 (4). Musc ular power is the maximum force one ca n generat e during a specific movemen t a t a specified vel ocity. I t is co nsider ed a pr edictor of functio nal capaci ty, as i t is associated with t he e xecu tion of ac tivities of daily living such as climbing st airs, standing up fro m a chair, or walking. Previous studies have report ed tha t power diminishes more t h an strength ove r time (5). Bo th s treng th an d powe r t raini ng have be en impl ement ed to p reven t t he risk of falls an d improve the bal ance or walking capacity in older adults (2,3). Resistance t raining (RT) is one of th e main str at egies used to preve nt d ec reased functional capacity and has b een d emonstr ate d t o be effective in comba ting age-induce d muscle atrop hy (sarcopenia), the risk of falls, and fragility (6). It has been obse rved tha t compa red with RT with concentric-bas ed ex ercises, RT with eccentric-bas ed ex ercises le ads to gr eat er maximal str engt h with less muscle activation an d lower me tabolic cost, and a grea te r increas e in muscle mass (7,8). The most tradi tionally used RT method i n community health is the gravita tional method, in which resistanc e is opp osed through fr ee weig hts by blocks in cabl e machines . The gr a vitational meth od is considered on e of the most functio nal resista nce tr aining appro aches (9). One of the mai n

of th e gravita tion al metho d is that t he workload applied in the conce n tric phase of th e lengthening-shor teni ng cycle limits the muscle capacity progressi on in th e ecce ntric phase . This fact limits th e po ten tial of this met hod f or gene rating the improvemen ts associa ted with eccen tric training. In cont rast , in the iso-iner tial tra ining me thod, the resis tance is gen era ted by an is o-inerti al device , where th e iner tia of a rot ating mass pr ovides the workload . Unlike th e gravita t ional system, the iso-inertial me thod can provide a grea t er force in the eccent ric phase of an exercise , known as eccentric overl oad. Owing to the force- genera ting system of iso-inertial system s, high workloads All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint can be applied for b oth phas es of a given action compared to gravit ation al systems, where eccentric overlo ad can only b e achieve d with ex tern al assis tance . A noth er be nefit of the iso- inerti al meth od is tha t, when t he load i n creases or fa tigue app ears , the ex ecution speed is reduc ed but th e acti on is not inte rrup ted (10). This allows a more fluid movemen t (i.e., self-adaptiv e resistanc e) than gravita tional syst ems' in terr upt ed movements . Marot o-Izqui erdo et al . conduct ed a s ystematic revi ew to evalua te the effects of iso-inertia l training am ong athl et es and h eal thy sub jects, rep orti ng an incr eased muscle str e ngth, powe r and size (11). Mo re recen t s tudies have also focused on o lder adul ts. These studies showed improvements in p ostur al con trol, max i mal isomet ric st rengt h, o r isokin etic po wer in par ticipants who used iso-inertial systems compar e d to those who tr ained with fre e weights (12,13). Iso- inerti al training has also shown positiv e effects on metab olic varia bles such a s lipid pr ofiles o r maximal volume o xygen consumptio n (14,15). However, no study has compa red the effects of iso- inerti al and gr avitati onal t raining on po wer when pe rforming functional ex ercis es and on physical performance vari ables in middle-old er a dults. The main objective of this study was to evaluate the effectiven ess of an iso-inerti al resist ance training progr am on eccent ric power compared to that of th e same progra m execut ed with gravitation al r esistanc e in physically act ive middle-older adul ts. The seconda ry objective was t o compare th ese two pr ograms in concent ric power, physical performance, and risk of falls.

Trial design and setting This was a parallel-group, randomised co ntroll ed trial (allocat ion rati o 1:1) with a blinded outcome assessment pe rformed a t the Espai Espo rt Welln ess Cente r gymnasium (Granolle rs, Spain). We followed th e Consolida ted St andar ds of Repo rting Tri als (CONS ORT) to p r oduce t his re por t (16). Participants We recrui ted adu lts aged 57 years or ol der who were physically active. By “phy sically active” we considered tha t th ey were enr olled in t he gymnasium mention ed above and us ed th eir faciliti es with varying frequency. We exclud ed p articipan ts with oste oar ticular or acu te musculoskeletal injuries or systemic neurodeg ener ative d iseases. Rec ruitmen t was performed in c ollabora tion with All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint the administr ative s taff of th e gymnasi um, who cont acte d all members over 57 years ol d and invited them to par ticipat e. Interventions Participants had t o complet e a 6-week program (2 sessions/week separated by at least 48 hours) using either a n iso-iner tial or a gravit atio nal resista nce device. The sessions s tar ted with a warm-up th at consis ted of 1) 4 minut es of mod era t e ae robic ex ercise (treadmill, elliptic al bike, or st atic bike) , 2) active str etching ex ercises for 6 se conds each (hip adductors , hamstrings, gastrocn emius, quadriceps, and glut eus), and 3) 6 -8 repetitions of each of the thre e in terven tion ex ercises with out any resist ance so tha t par ticipan ts beca me familiar wit h them. Then, rega rdless of th e assigned gro up, participan ts had to pe rform th e same t hree in terve ntio n exe rcises (forward lunge, side lunge , an d forward lunge with row (see Figure 1) . For th e forward lunge and the fo rward lung e with row, t he par ticipan t was plac ed fron tally on th e tr aining device , whereas for the sid e lunge the par ticipa nt was placed sideways on the device (homolat erally on the scrolling limb). For the forward and side lunge, we used a weigh t bel t placed on the waist . Fo r the forward lu nge with row, we us ed a h and grip and th e pull was perfo rmed wit h the upp er limb homolat eral t o the displ aced lower limb . Each exercis e was performed with b oth li mbs (Figure 1). After seve ral rep eti tions to ini tiat e th e flywheel impulse, the e xercis es wer e performed to accelera te th e r ota tion of th e flywheel i n the concen tric action , an d dec eler at e i t in the eccen tric action. Th e study inves tigato rs inst ructe d particip ants to p erform t he e xe rcises a t a given in tensit y according to th e Bo rg Rati ng of Perceive d Exer tion (RPE) scale (0-10, where 0 me ans no e xe rtion a t all and 10 means ma ximal exe rti on) (11) . The volume , in tensity, and difficulty inc reased over time (see Table 1). The load was identical for all participan ts, but e ach particip ant adjuste d th e execu tion spee d of each exe rcise to ac hieve the desi red RPE. At weeks 4 and 6, the exe rcises included variati ons in the di recti ons and distances of the lu nges tha t were mark e d on the floor . Tabl e 1. Progr es sio n of th e i nt erve nti on pr ogr am. Sessions Load Intensity Fr om 1 to 4 2 set s of 6 t o 8 rep eti ti ons RPE 3 t o 5 5 and 6 3 set s of 10 rep eti ti ons RPE 3 t o 5 7 and 8 3 set s of 10 rep eti ti ons* RPE 3 t o 5 9 and 10 3 set s of 10 rep eti ti ons* RPE 7 t o 8 All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint The iso-iner tial gr oup us ed th e Nessine rt ial® conical pull ey with 6 iner tial loads. T he rop e r egulat or was placed at th e lowest possible posi ti on so that t he rop e rolle d in a large dia meter , providing more spe ed bu t less dr ag. The par ticipa nt was placed at a dist ance from the d evice det ermine d individually when the trac tion string re ached the maximum t ension at t he star t of the execu tion o f each e xercis e. The gravita tional group us ed an MFT CSX-5000 device (weight: 3,7 5 kg). Participant s were inst ructed not to pe rform any o ther resist ance t raining for t he lowe r limbs during the interven tion p eriod . All par ticipan ts wer e sup ervised by one of the study inves tigato rs o r th e ce nte r’ s instruct ors un til the p art icipants were shown to b e au ton omous. Fr om th at moment , th e s essions were perform ed without supervision . A ddition ally, pa rt icipants we re provided with documen tary informatio n through images and videos of the e xercis es. In case of doubts, they could contac t the investiga tor s by phone. Outcomes Outcomes wer e assessed a t th e gymnasium’s facilities before the int er vention (T0) and immediately aft er the compl etio n of it (T 1). The star ting limb for each e xercis e wa s randomised for each subject. The primary ou tcome was t he powe r in t he eccen tric phas e of each ex ercise . It was measure d wit h both iso-ine rtia l and gr avitati onal resi stance d evices using a r ota tory an d a linea r encod er (Chronojump Boscosystem®)(17), respec tively. We use d th e fre e softwa re Chr on ojump to r ecord the da ta. This softwar e is associate d with the open h ardwar e Chronopic V.3. The seconda ry outcom es wer e 1) power in t he co nce ntric p hase of each exe rcis e, measu red wi th both iso-ine rti al and g ravita tional devices; 2) ph ysical perform an ce, me asure d using the Shor t 11 and 12 3 set s of 10 rep eti ti ons* RPE 7 t o 8 RPE, rat e of perc eiv ed exer tio n; * l un ge s p erf ormed wi th diff ere nt len gth s an d d irect io ns All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint Physical Performance Ba tte ry (SPPB) (18 ), which consists of a ba l a nc e t e s t , a spe ed of m arch test , and a five ti mes sit-to-st an d test ; and 3) risk of falls , assessed through the Get Up and G o test (19) . These tes ts are explai ned in Suppl ement ary File 1. We also collec ted anth ropome tric a nd sociodemograp hic variabl es: d ate of b irth, we ight (kg), height (cm), sex (man/woman), and wor k status (working/retired). Sample size We performe d the sample calculati on using R statistical software (“pwr” pack age). Based on a previous study t hat comp ared is o-iner tia l and gravita tional resist ance training p ro tocols in a thle tes using an iso-in erti al d evice (10), we esti mated an effect siz e a nd a sta ndard de viation of 202 W and 153'97 W, resp ectively, for the p ri mary outcome . No simila r studi es were found tha t used a gravitation al system for powe r ass essment. Assuming alph a = 0.05, a b eta = 0.1, and a 10% dropou t rat e, th e sample size was 30 par ticipants (15/group). Randomisation (Sequen ce ge neration, A llocation co ncealm ent me chanism, Im pl ementation) and blinding We perfo rmed ra ndomisati on in blocks of 4 and stratifi ed by sex and age (57-63, 64-70, 71 or more). The rand omisatio n sequ ence wa s matched by th e adminis tra tive s taff o f the c ent er wit h the pa rticipa nts' m embership n umbers according to the p articip ants’ recrui tm ent o rder . In this way, the particip ants and r esea rchers w ere no t aware of th e allocati on until th e training program start ed. Give n the na ture of the in terven tion, nei ther pa rticipa nts nor investiga to rs monitoring th e training pro tocols may be blinded to the allocation . However, th e outcome assess ors did not know the assignmen t of each par ticipant . Statistical methods For t he s tatis tical analysis, we used R software. Ini tially, we pres ent ed d escri ptive da ta of all subjects who wer e r andomised and who complet ed t he s tudy. To analyse the r esults for the stud y outcomes, we used lin ear r egression models where t he dep enden t variabl es were the cha nge scores of each ou tcome, d efined as th e T1 minus the T0 value, and th e inde penden t variabl es were the all ocatio n group (iso-inertial o r gravitational), th e limb, and some demo graphic variables (age and sex). We ch ecked differen t m odel applica tion assumptions (line arity, homoscedastici ty, normality, and ind epen dence). As we o bserved tha t th e charac teris tics of the lost to follow-up All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint participan ts wer e similar to thos e of th e par ticipan ts who comple ted the study , we pe rformed a complete case analysis. We repo rte d the adjusted difference of mea ns betwe en groups along wit h its 95% confidence int erval and the p-value of the c omparison . The significance le vel was 0.05. Th e R scripts have bee n publicly shared (20).

Betwe en 10 N ovember 2023 and 28 F e bruary 2024, we recrui ted 47 par ticipan ts. Thr ee of them refused t o par ticipat e, ther efore w e ran domised 44 par ticipan ts: 21 to the iso-inertial (IN) and 2 3 to the gr avita tional (GR) t raining gro up. Sevente en p ati ents w ere lost to follow-up (n=6 I N gro up , n=11 GR grou p). The main re asons for th ese were 1) failure to a tt end tr aining ses sions (n=8) and 2) occurrence of person al (n=4) or mu sculoskeletal pr oblems (n=4). Finally, 27 participant s completed the pr ogram (n=15 IN group , n=12 GR group) (Figure 2). The mean (SD) age of par ticipants was 6 3.81 (6.65) years, 56.81% (n=25) of the participan ts wer e females and 43.18% (n=19) wer e males. The baselin e charac teris tics of all pa rtici pants wer e simila r to the cha ract eristics of thos e who completed the stu dy (Table 2). Tabl e 2. Ba se lin e c harac teri stic s of part icip an ts. Total participants include d (n=44) Participants with full program complete d (n=27) IN gr oup (n=21) GR group (n=23) IN gr oup (n=15) GR group (n=12) Age Years (me an, SD) 65, 6,36 62,74, 6,87 64,53, 6,9 62,25, 6,61 Gender F e m al e ( % ,n ) 61,90%, 13 52,17%, 12 53,33%, 8 66,67%, 8 Mal e ( %,n) 38,1%, 8 47,83%, 11 46,67%, 7 33,33%, 4 Wei ght Kilo grams (m ean , SD) 68,18, 10,28 73,09, 11,18 68,41, 9,35 70,67, 0,59 Height Met ers (me an, SD) 1,65, 0,08 1,69, 0,08 1,65, 0,06 1,67, 0,1 Status Active (%, n) 47,62%, 10 65,22%, 15 53,33%, 8 66,67%, 8 Retire d ( %,n) 52,38%, 11 34,78%, 8 46,67%, 7 33,33%, 4 GR, gr avit ati onal ; IN, is o-ine rt ial ; SD, S tan dar d d evi ati on Primary outcom e The improvemen t in th e powe r in th e e ccentric ph ase evaluat ed wit h th e iso-in ertial system wa s great er in the IN gr oup for all ex ercise s (Table 3). However, ther e wer e sta tis tically significant All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint differences on ly for the side l un ge . F o r th e forward lu nge , th e me an pow er in th e eccen tric phas e at T1 was 42.67 W in the IN group a nd 35.59 W in the GR gr oup. The differe nce betwe en group s was 3.99 W (95% CI: -3.99 t o 11.33 , p= 0.28). For th e side lun ge , th e mean ecc entric power wa s 51.06 W and 40.22 W in th e I N a nd G R groups, r espectively (be tween-gro up dif ference: 8.50 W, 95% CI: 2.13 to 14.87; p=0 .01). The me an eccent ric power for th e forward lun ge with row was 128.39 W and 102.41 in the I N and GR groups, resp ectively (betwe en-group dif ference: 14 .07 W, 95% CI: -2.07 -to 30.20, p=0.09). Both gr oups ha d similar power changes in th e eccent ric phase evalua ted with the gr avitati ona l system (Table 3). F or the forward l un ge , th e mean eccen tric p ower was 24 .99 W and 26 .08 W in the IN a nd G R groups, resp ectively (be tween-group difference : -0.34 W, 95% CI: -2.86 to 2.18, p=0.79). For th e side lung e, the mea n eccentric power was 23.03 W in the IN an d 21.75 W in the GR group (be tween-group differ ence: 0 . 56 W, 95% CI: -1.53 to 2.65, p =0.59). T he forward lu nge with row showed a m ean ecce ntric p o wer of 55.58 W and 60.08 W in the I N and GR groups, respectively (betwe en-group differ ence: -2.99 W, 95% CI: -13.48 to 7.51, p=0.57). Table 3. In tr a and inte r-g roup analys is of p o wer change s in the e ccen tr ic phase. Power in eccentric p hase (W) GR G roup IN Group Differ ences between groups Signi fica nce Evalu ati on syst em Exercise mean (SD) mean (SD) mean (SD) mean (SD) dif_ adjus te d (95% CI) p-val ue T0 T1 T0 T1 Iso-ine rt ial Fo rw ard lunge 19,12 (9,37) 35,59 (21,11) 21,14 (9,52) 42,67 (15,78) 3,99 (-3,35 to 11,33)* 0,28 Side lunge 25,52 (12,21) 40,22 (15,25) 26,75 (12,04) 51,06 (19,37) 8,5 (2,13 t o 14,87)* 0,01 Fo rw ard lunge with r ow 65,89 (45,58) 102,41 (62,81) 71,89 (40,08) 128,39 (51,49) 14,07 (-2,07 to 30,2)* 0,09 Gravi tat iona l Fo rw ard lunge 21,52 (6,36) 26,08 (8,03) 21,53 (6,50) 24,99 (5,41) -0,34 (-2,86 to 2,18) 0,79 Side lunge 19,11 (4,26) 21,75 (4,22) 19,39 (4,07) 23,03 (4,40) 0,56 (-1,53 to 2,65)* 0,59 Fo rw ard lunge with r ow 42,37 (16,38) 60,08 (27,24) 42,41 (18,57) 55,58 (16,79) -2,99 (-13,48 to 7,51) 0,57 W, w at ts; GR, g ravi ta ti onal; IN, is o-ine rti al; S D, standa rd d evia tion; CI, c onfiden ce inte rva l ; *fav o rs is o-ine rti al group Secondar y outco mes All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint The changes in concentric muscle power evaluated with bo th iso-iner tial and gra vitational system s were similar in both grou ps (Table 4). T here wer e also no rema rkable be twee n-group difference s in physical performance and risk of falls (Table 5). Table 4. In tr a and inte r-g rup analy sis of po we r changes in th e con cent ri c phas e. Power in concentric ph ase (W) GR G roup IN Group Differ ences between groups Signi fica nce Evalu ati on syst em Exercise mean (SD) mean (SD) mean (SD) mean (SD) dif_ adjus te d (95% CI) p-val ue T0 T1 T0 T1 Iso-ine rt ial Fo rw ard lunge 21,74 (9,18) 39,51 (24,24) 26,55 (10,74) 42,29 (14,45) -3,23 (-10,65 to 4,19) 0,39 Side lunge 25,49 (12,40) 41,09 (19,00) 28,65 (12,66) 48,02 (17,43) 1,70 (-6,08 to 9,48)* 0,66 Fo rw ard lunge with r ow 72,19 (48,28) 106,71 (60,33) 79,91 (44,43) 126,10 (50,11) 5,65 (-10,12 to 21,43)* 0,47 Gravi tat iona l Fo rw ard lunge 19,14 (5,43) 21,74 (4,74) 19,91 (5,27) 21,92 (5,09) -0,32 (-2,70 to 2,06) 0,79 Side lunge 17,43 (3,61) 18,42 (3,46) 17,45 (3,04) 19,60 (2,81) 0,97 (-0,25 to 2,18)* 0,12 Fo rw ard lunge with r ow 43,44 (20,31) 71,44 (48,66) 52,60 (27,81) 82,04 (37,79) 3,26 (-16,72 to 23,24) 0,74 W, w at ts; GR, g ravi ta ti onal; IN, is o-ine rti al; S D, standa rd d evia tion; CI, c onfiden ce inte rva l ; *fav o rs is o-ine rti al group Table 5. In tr a and inte r-g rup analy sis of physi cal fitne ss and risk of fall s changes. Phy isica l f itness GR G roup In G roup Differ ences between gro ups Signi fica nce Test Outc ome mean (SD) mean (SD) mean (SD) mean (SD) dif_ adjus te d (95% CI) p-val ue T0 T1 T0 T1 SPPB Sc or e (0 t o 12) 10,92 (1,16) 11,67 (0,65) 10,85 (0,80) 10,92 (1,32) 0,66 (-0,38 to 1,69) 0,20 Balanc e (sec) 3,83 (0,58) 4,00 (0,00) 4,00 (0,00) 3,92 (0,28) 0,25 (-0,13 to 0,63) 0,19 Walking speed (sec) 3,18 (0,59) 3,09 (0,46) 3,18 (0,62) 2,86 (0,46) 0,22 (-0,19 to 0,63)* 0,28 FTSST (s ec) 12,25 (2,01) 10,84 (2,18) 12,66 (2,08) 11,30 (2,36) -0,24 (-1,42 t o 0,95) 0,68 Risk of f alls GR _G roup In_G roup Differ ences between gro ups Signi fica nce Test Outc ome mean (SD) mean (SD) mean (SD) mean (SD) dif_ adjus te d (95% IC) p-val ue All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint T0 T1 T0 T1 GUG Sec onds 8,29 (1,60) 8,04 (1,02) 8,33 (1,28) 7,67 (1,20) 0,37 (-0,77 to 1,52)* 0,51 GR, gravitational; IN, iso- inertial; SD, standar desviation; CI, confidence interval; SPPB, Short Physical Performance Bat tery; sec, seconds; FTSST, f ive times s it to stand test; GUG, Get up and g o test; *favors to i so-inertial group.

Our resul ts indicat ed tha t iso-inerti al tr aining led to grea ter pow er gains in th e eccentric phas e than gravita tion al trai ning when power was assessed with the iso-ine rti al syste m. However, with the gravita tional syst em evaluatio n, the two types of training perfo rmed similarl y. In addition , we observed n o differe nces in the concen tri c power, p hysical perfo rmance, and risk of falls. This is the first study in middle-ol der adults to 1) c ompare the effectiveness of iso-ine rti al and gravita tional resistanc e t raining on the power of a co ordinat ive ac tion, 2) separ at ely analyse the power in the eccentric and co ncent ric phas es of each ex ercise, and 3) assess powe r using b o th an iso-iner tial and a gravita tional device r egardl ess of the particip ant ’s traini ng group. Despite the impor tance of muscular power in middle-older adul ts (4), only two studies have compared iso-iner tial and gravit ation al t raining using this parame ter . Flore ani et al. evaluat ed th e maximal explosive powe r when perfor ming a leg press ( force platform), observing that bot h training app roaches l ed to similar gains ( +11.1% IN, +13.4% GR)(7) . In a similar st udy, Sañudo e t al. repor ted a 63% incre ase in power outp ut in the IN gro up (with no d ata from t he GR group) (21). These findings are d ifficult to compa r e with ours fo r thr ee reaso ns: 1) differen t evalua tion systems, 2) different training pro tocols, and 3) no concentric-eccent ric phase differen tiati on when measuring power. Firs t, the improvem e nts by Floreani et al. might be similar to ours when power was assessed using the gravi tatio nal system, but ve ry different from those fro m the iso-iner tia l system assessment, whe re ou r gains in b oth groups wer e much grea ter and favou red th e IN gr oup. These resul ts are co nsisten t with th e fac t tha t th ey evaluat ed power wit h a nonis o-inerti al system. However, Sañudo e t al. also evalua ted p ower using a noniso-inertial system and their resul ts ar e remarkably differen t from ours. In gen eral, we beli eve tha t the iso-ine rtia l system evaluati ons reflect the powe r gains m ore accura t ely than th e gr avitati onal evalua tions because of the eccentric overloa d gen era ted by the de vice. Ther efore, we suggest using iso-in ertial devices to evaluat e the changes gen era ted by eccentric overl oad tr aining. Secon d, the t wo studies above proposed a tr aining program b ased on a single analytical exe rcise (squat o r le g exte nsion). Ou r All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint protocol is functional beca use it invol ves trunk stabilizat ion and the main upper and lower ext remity muscle groups, and combines resistanc e and high-velocity e xercises . This protocol al igns with current posi tion st atem ents and c onsensus guidelines for physical activit y in older adults, which recommend a mul timodal pres cription tha t includes aer obic, st reng th balanc e, a nd flexibility (22). In this regard , training protocols should always includ e functi onal ac tions wi th maximal transfe rence to middle-ol der ad ults’ activities of daily living. Third, the two studies above evaluat e powe r only in absolu te t erms, making no differ ence b etwe en eccent r ic and conce ntric phases. Given t he implica tions of ecc ent ric actions for activiti es of daily living, a separa te analysis of power in th e eccent ric phas e should always be includ ed in futur e stu dies tha t evaluat e traini ng programs in middle-olde r adults (23–25). The IN gro up obt ained gr ea ter p ower i n the ecc entric p hase values than the g ravitati onal grou p when power was assess ed with the is o-inerti al system. Thes e resu lts ar e co nsistent wi th th e theor etica l basis of iso-iner tial tra ining, which allows maximal concen tric and eccentric muscle actions, wi th bri ef episo des of eccent ri c overload (10). Previous studi es have repor ted tha t the peak force gener at ed in the eccen tric phase of movement may be 15-30% g reat er th an tha t produced in the p receding conce ntric a ction due to th e elas tic ene rgy storage characte ristics o f the iso-ine rti al system (26,27). In this r egard, a nimal studi es have d emonst rat ed tha t incr ease d prote in synthesis (vinculin, titin, and n ebulin) is linked to physiological tissue adapta tions and elastic prop er ties in resp onse t o eccent ri c work (28 ). No differences be tween grou ps were o bserved in eccent ric power for the gra vitational syste m evaluation . This might be b ecause of t he limited p ower gen era tion duri ng th e eccent ric phas e when gravita tional t raining is perfo rmed. Pr evious stu dies in a thle tes have r epo rte d improvements i n powe r favoring iso-ine r tial training wh en compar ing iso-iner tial and gravita tion al training, however, bo th groups w ere eva luated only with the iso-iner tial syst em (11,29–31). Using a single tool could a tt ribut e the resul ts to the par ticipants ' familiari ty (and l ack ther eof) with the iso-inertial syst em. Ass essing our pa rtic ipants with bo th systems all owed us t o avoid this bias . Indee d, if the differences favoring the iso-inertial t raining group were a consequence of familiarisation wit h th e tr aining meth od , the GR group would h ave ob tained m ore powe r on th e gravitation al system evaluati on. How ever, the gravi tati onal system evaluati on s howed almost no differences be twee n th e groups . This fi nding confirms tha t th e ecc entric overl oad gene ra ted by iso-inertial traini ng genera tes t rue highe r power values in the eccent ric phase of t he action . All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint Although the re we re n o significant diff erences be tween gr oups, we found t h at all par ticipants improved thei r physical performanc e an d reduced th eir risk of falls. These r esult s are in line with the syst ematic review of traini ng pro grams in old er a dults tha t r epor ted i mprovements i n functional perfo rmance for all pa rticipa nts, with a small advant age for eccen tri c-based compare d to concen tric-base d e xercis es (32). Ano t her r eview re por ted imp rovemen ts in u nipedal b alance in older adul ts who used an iso-ine rtial device compared to thos e who used weights (11). The authors a tt ribut ed this r esponse to incr eased t endon s tiffness and neuromuscul ar tra nsfer to th e planta r flexors . No tably, th ese reviews a re focused on analytical ex ercises. Howe ver, our pro toco l proposed a mo re func tional appr oach . First, we used lunges b ecause th ey involve comple x functions such as decelera tion of a limb, force absorpti on, and cont rolling movement agains t an ext ernal forc e (33) . Notably, th ese functions are key compon ents of an eccen tr ic action (25). In addition , all ex ercises accen tua ted trunk stabiliza tion, which should always be a factor t o conside r when developing int erventi ons for middle-older ad ults. Som e studies have re porte d tha t cor e stability training fo r olde r adul ts can also improve bal ance an d coordi nati on, an d decreas e th e risk of falls (34 ). On the o the r hand, few studies have c ompared t he effects of performing th e same functional exe rcises with different types of resista nce. Madrug a-Parera e t al. evalu at ed th e effectiveness of functional ex ercises fo r han dball player s tha t we re b iomechanically iden tical f or t he two s tudy groups and only the type of r esistanc e ch anged (35). Our p rot ocol was based on t his approach . We suggest tha t futu re s tudies i ncorpo ra te this me thodology when evalua ting the differences betwee n trai ning methods to avoid perfo rmance biases in th eir r esults. It is worth men tioning th at t he scales u sed for evaluating physical pe rformance and risk of falls lacked sensitivity for the type of partici pants included, as we encoun ter ed a ceiling effect. Fo r example , th e par ticipan ts’ mean bas elin e SPPB score was 10.88 out of 12 poin ts, indicating a grea t physical condition. A similar ceiling effec t was noted in ano ther st udy, tha t claimed tha t the Berg scale could not pr edict the risk of falling at high levels of balance abili ty (36). As other s tudies do , we suggest tha t t ests and scal es origin ally built for middle-old er a dults should be modified fo r physically active middle-older adul ts. Strengths and limitations The strengths of this study include 1) the randomised cont rolled t rial design, 2) the pragmatic design, which is ide al for tes ting th e ef fectiveness of in terven tions u nder re al-life conditions , 3) All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint the ou tcome evalua tions with two dif ferent systems t o avoid familiarisati on effects, 4) the functional tr aining program, and 5) the i nclusion of identical e xercis es for the two groups. This research also has some limit ations . First, 38% of participan ts were lost to follow-up. However , their char acte ristics wer e simila r to th ose of those who compl ete d t he s tudy . Fut ure res earch should place more emph asis on closer monitoring of int erventi ons. Addi tionally, we did not collec t data on par ticipan t satisfacti on, which would have allowed us to d et ermine w hethe r th e gre ate r losses in the G R group wer e du e to dis satisfaction with the tr aining d evice. Fi nally, we di d no t measure fur ther physiological p arame te r s involved in functional and struc tural a d apta tions. Fu tur e studies could includ e th ese pa rame ters to e xplor e th e unde rlying mechanisms behind th e effect s of iso-inertial and gr avitati onal t raining. Clinical implications This study helps improve the unde rst anding of th e effects of iso-ine rti al a nd gravita tiona l resistanc e tr aining, l eading clinicians to recommend mo re effective tr aining pr ograms for olde r adults. Addi tionally, we pr ovide st rong empirical da ta tha t supp ort ori enting r esistance tr aining towards comple x e xe rcises involving complex coo rdina tive acti ons (rath e r than analytica l exe rcises) with a t ransfer to daily activ ities such as walking o r going up an d down stairs . This approach may incr ease older adul ts’ au t onomy and th erefo re pr omot e heal thie r longevity. Finally, we warn ab out the ceiling effect of t he c urren t clinical evalua tion tests and sugg est avoiding thei r use in t he physically act ive middle-old er adul t po pulati on. Inst ead, w e prop o se to use powe r assessments in clinical practice to monit or the improvemen ts associat ed with re sistance trai ning programs.

A 6-week iso-iner tial t raining p rogram led to gr ea ter p ower in the eccent ric phase gains t han gravitation al trai ning when power was assessed with an iso-inertial system . However, th ere wer e no differences betwe en th e two method s for the gravitation al system evaluati on or for concentri c power, p hysical pe rformance, and risk of falls. R egardless of th e traini ng syste m, the r esistanc e training prog ram rema rkably improved t he resul ts for all outcomes . Other information All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint

The autho rs warm ly thank the staff of Espai Espor t Well ness (Gran ollers , Spain) for allowing us to car ry out this p roject in th eir facilit ies and h elping us re cruit par ticipan ts and monitor the in terven tion . Contributors: Conceptualizati on: AC, D R, MMP, DB. Wr iting – o riginal dr aft: AC, DB. Wri ting – review & editing: AC, DB, DR, MMP, VZ and FD. Me thodology, Sof tware, Data Cur ation a nd Forma l Analysis: DB and VZ. Reso urces: DR, MP. Investigati on: AC, DB, DR, FD. Supe r vision and project administra tion: AC, DB. Funding: None of the autho rs receive d funding for this rese arch. Competing inter ests : The aut hors decla r e no conflicts of inter est. Patient and public involveme nt: Patients and/or the public wer e no t involv ed in t he d esign, conduct, re por ting, or dissemina tion pla ns of this research . Ethics approval: This study was app r oved by t he Drug Rese arch E thics C ommitte e of the Universita t In ter nacional d e Cata lunya (Code: FIS-2023-03). The prot ocol c an be found in Supplemen tary File 2. Particip ants provi ded informed consen t to par ticipat e in the study befor e taking part . Provenance an d pe er re view: Not commissioned; e xt ernally pe er-reviewe d. Data availability statement: Data were stored and enco ded in thr ee Excel files to protec t confidentiali ty before, du ring, and aft er the study. The first of th ese files cont ains the pe rsona l data of th e pa rticipan ts (name and surnames, age, and s ex), is accessi ble only to the administra tive staff of the cen ter , and s erved only to manag e the recrui tment o f the particip ants . The second and third files are manag ed entir ely by the resea rch team and cont a in the registry of all th e stu dy outcomes. In these files, p articipan ts wer e id entifie d by a code . O nly the rese arc h team can rel ate th e da ta coll ecte d in the study to th e iden tity of the par ticipan ts, which will not b e available t o anyone exc ept in the event of a medical eme rgency or legal requi re ment. These tw o files have been shar ed in a public re posit ory (20). Study Registration: This study was registered a t Clinicaltri als.gov (NCT06160089). Author information : David Blanco, PhD ([email protected]); Marc Madr uga-Parera, PhD , ([email protected]); Victor Zár at e-Lozano, B.S . (vzarat [email protected]); Fl ora Dantony, Ms U ([email protected]), Daniel Romero-Ro drí guez, PhD([email protected]) All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint Work address : C/ de Josep Truet a, 0819 5 Sant Cugat del Vallès, Barcelo na, Spain . List of references 1. Chuang YF, Ch en CC, Hsu MJ, Huang NJ, Huang YZ, Chan HL, e t al . Age r ela te d changes of th e motor excit abiliti es and cen tral and periph eral muscle st rength . J Elect romyogr Kinesiol . 2019;44(November 2018):132–8. 2. Suchomel T J, Nimphi us S, S tone MH. The Impor tance of Muscular S tr ength in Athl eti c Performance. Spo rt Med. 2016 Oc t 2;46(10):1419–49. 3. Foldvari M, Clark M, Laviolette LC, Bernst ein MA, Kalito n D, Castaneda C, et al. Association of muscle power with func tional sta tus in community-dwelling elde rly women. Jo urnals Ger ontol - Ser A Biol Sci Me d Sci. 2000;55(4):24–7. 4. Keller K, Engelh ard t M. S tr ength and muscle mass loss with aging process. Age and str ength loss . 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Ef fectiveness of eccent ric-biased ex ercise inte rventio ns in reducing th e incid ence of falls and impr oving functional p erformance in old er a dults: a systema tic review. Vol. 13, Europe an Ge riat ric Me dicine. Springe r Science and Busin ess Media Deutschlan d GmbH; 2022. p. 367–80 . 33. Jönhagen S, Halvo rsen K, Benoi t DL. Muscle activation and leng th changes during two lunge exe rcises: Implica tions for re habilit atio n. Scand J Med Sci Spor t. 2009 Aug;19(4):5 61–8. 34. Haruyama K, Kawakami M, O tsuka T. Effect of Core St ability Tra ining on Trunk Functio n, Standing Balance , and Mobili ty in S trok e Patie nts: A R andomiz ed Cont rolled Tr ial. Neur oreh abil Neur al Repai r. 2017 Mar 1;31(3):240–9 . 35. Madruga-Pare ra M, Bisho p C, Fort- Vanmeerha eghe A, B eat o M, G onzalo- Skok O, Romero- Rodríguez D. Effects of 8 Weeks of Isoin ertial vs. Cable-R esistanc e Training on Motor Skills Performance a nd In te rlimb Asymmet rie s. J s tr ength Cond Res . 2022 May 1 [cited 202 4 May 2];36(5):1200–8. 36. Lee DK, Kang MH , Le e TS, Oh JS . R el ationships among the Y bal ance tes t, Be rg B alanc e Scal e, and lower limb st rength in middl e-aged and old er femal es. Brazili an J Phys Ther. 2015;19(3):227– 34. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint Figures and tables Figure 1: Interventi on ex ercises : a) forward lunge, b) side lunge, and c) forward lu nge with row. Figure 2: CONSORT flow diagram. Table 1: Progression of the int erven tion program. Table 2: Baseline cha ract eristics of par tic ipants. Table 3: Intra and int er-group ana lysis of power changes in th e eccent ric phase . Table 4: Intra and int er-group ana lysis of power changes in th e concent ric phase . Table 5: Intra- and in te r-group analysis o f physical fitness and risk of falls. Supplementary Files Supplem entary File 1 : Explanation of th e Short Physical Performance Ba tt ery an d Get Up an d Go tests . Supplem entary File 2: Study protocol ap proved by the Ethics Committ ee. All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint All rights reserved. No reuse allowed without permission. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprintthis version posted May 13, 2024. ; https://doi.org/10.1101/2024.05.13.24307107doi: medRxiv preprint