Gender differences in body composition, motor performance and blood biomarkers in older adults OUTLINE

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1 Gender differences in body composition, motor performance and blood biomarkers in older adults Mati Pääsuke Institute of Sport Sciences and Physiotherapy, University of Tartu, Estonia International Symposium Current Research and Future Perspectives in Exercise Physiology, November 8, 217, Tartu OUTLINE Background Research Objectives Materials and Methods Results Conclusions Acknowledgement 1

2 Aging-related changes in skeletal muscle and bone interactions SARCOPENIA Motor unit remodelling: Motor unit number Muscle fibre number Muscle-tendon unit remodelling: Tendon sffness Muscle pennaon angle Muscle fascicle length BACKGROUND Aging is associated with a progressive loss of skeletal muscle and bone mass, and strength referred to as sarcopenia and osteopenia, respectively. Muscle mass Muscle strength Physical performance Prevalence: Up to: 13% in6-7 yr-olds 5% in > 8 yr-olds M=W Common factors: Physical activity Nutritional factors Low-grade inflammation Oxidative stress Hormonal modifications Anabolic resistance Muscle-tendon unit OSTEOPENIA Bone mass Bone strength Bone density Prevalence : Up to: 54% in6-7 yr-olds 81% in > 8 yrs yr-olds W>M Bone remodelling: Osteoblast acvity Osteoclast acvity Changes in bone geometry Changes in bone architecture Age-related skeletal musclebone interactions which still remains poorly undestood: Gender-specific associations between diagnostic criteria for sarcopenia and bone mineral density. Gender-specific associations between muscle tendon unit mechanical properties and mobility in older adults. Gender differences in age-related bone remodelling Gender differences in circulating markers of bone remodelling in older adults. Adapted by: Tagliaferr et al., 215; Demontiero et al., 214, Lopes et al., 29) RESEARCH OBJECTIVES To determine gender-specific associations between different diagnostic parameters for sarcopenia and whole-body bone mineral density (WBMD) in healthy older adults. To evaluate gender-specific associations of Achilles tendon stiffness and triceps surae muscle architecture with plantarflexor muscle strength and mobility in older adults. To evaluate gender differences in circulating markers of bone remodelling in older adults. 2

3 MATERIALS AND METHODS Subjects European (EU) cross-sectional ageing study MYOAGE cohort consisted of healthy: older men (OM) and older women (OW) aged years (5% women) young men (YM) and young women (YW) aged 18-3 years (52.2% women) The study included 454 participants (283 older and 171 young adults) from: Leiden, The Netherlands (75 older and 35 young) Jyväskylä, Finland (65 older and 34 young) Tartu, Estonia (71 older and 39 young) Paris, France (3 older and 35 young) Manchester, UK (42 older and 28 young) The subjects were recreationally active, community-dwelling and they had body mass index (BMI) < 3 kg/m 2. All measurements were performed according to standard operating procedures that has been unified at the study centres. The study was approved by ethics commitees at each institution. Measurements Body composition and bone mineral density - by dual energy X-ray absorptiometry (DXA) with a whole body scan. Triceps surae muscle architecture and Achilles tendon properties by ultrasonography Lower extremity motor performance - by: quadriceps femoris muscle and plantarflexor muscle isometric strength Timed Up and Go test 6 min walk test Blood biomarkers by overnight fasting blood samples McPhee J, Seppet E., Gapeyeva H, Pääsuke M et al. Biogerontology, 213, 14:

4 Subject characteristics (mean ±SD) Group OM n = 129 OW n = 143 YM n = 82 YW n = 89 Age (years) Height (m) Body mass (kg) BMI (kg/m 2 ) Body fat (%) 74.9 ± ± ± ± ± ± ±.6 # 64.6 ±.9# 25.1 ± ±.6# 23.6 ± ± ± ± ± ± ±.6# 62.2 ± 1. # 22.4 ± ±.7# BMI body mass index p<.5 compared with gender-matched young subjects p<.5 compared with age-matched men # Bijlsma AY, Gapeyeva H., Pääsuke M., Seppet E. et al. Osteoporos Int, 213, 24: RESULTS Age-related changes in body composition in men and women 4 % Difference compared to gender-matched young % 18% Body fat mass -7% Lean body mass -11% ASM -6% Total fat mass Total lean mass ASM ASM/height -7% Body mass (kg): OM = 78.3; YM = 76. OW = 64.6; YW = 62.2 ASMI ASM appendicular skeletal muscle mass ASMI appendicular skeletal muscle index = ASM/height 2 p<.5 compared to gender-matched young Body fat mass, leam mass and ASM presented in kg, ASMI presented in kg/m 2 Bijlsma AY, Gapeyeva H., Pääsuke M., Seppet E. et al. Osteoporos Int, 213, 24:

5 Gender differences in body composition characteristics in older adults Mass (kg) Fat mass Lean mass ASM ASMI -1% Total fat mass (kg) Total lean mass (kg) ASM (kg) -28% -31% ASM/height 2 (kg/m 2 ) ±.1-19% 6.5 ±.1 Sarcopenia by DEXA (kg/m 2 ): OM: ASMI<7.26 OW: ASMI<5.5 Baumgartner et al., 1998 ASM appendicular skeletal muscle mass ASMI appendicular skeletal muscle index = ASM/height 2 p<.5 compared to age-matched men Bijlsma AY, Gapeyeva H., Pääsuke M., Seppet E. et al. Osteoporos Int, 213, 24: Whole body bone mineral density (WBMD) and mineral content (WBMC) 1.4 Gender differences in older Differences compared to gender-matched young %Difference WBMD -5% -1% MeanT-scorevalues: OM: -.63 (normal) OW: (low or osteopenia), from them 11% osteoporotic (T-score WBMD > -2.5) WBMC -6% WBMC -15% WBMD (g/cm 2 ) WBMC (g) % -3% p<.5 compared to gender-matched young Coulson J, Gapeyeva H, Pääsuke M et al. Osteopor Int, 217, 28: p<.5 compared to age-matched men 5

6 WBMD associated positively with components of body mass in older Young men Older men Young women Older women p values were calculated with linear regression models for the association between components of body mass and WBMD with adjustments for age and country. p <.1; p <.1. Lean mass Fat mass Body mass BMD whole body bone mineral density Bijlsma AY, Gapeyeva H., Pääsuke M., Seppet E. et al. Osteoporos Int, 213, 24: BMD (g/cm2) BMD (g/cm2) Older men Older women WBMD positively associated with diagnostic criterias for sarcopenia inoldermenand women p values were calculated with linear regression models for the association between diagnostic measures for sarcopenia and whole body BMD with adjustments for age and country. p <.1; p <.1. ASM apendicular skeletal muscle mass ASMI appendicular skeletal muscle index = BMD whole body bone mineral density QF quadriceps femoris muscle ASM/height 2 ASM (%) QF strength ASMI Bijlsma AY, Gapeyeva H., Pääsuke M., Seppet E. et al. Osteoporos Int, 213, 24:

7 Age-related changes inachillestendon stiffness and triceps surae muscle pennation angle in men and women Ultrasonography MG Pennation angle SOL Achilles tendon stiffness % Difference compared to young Difference compared to young adults (%) MG medial gastrocnemius muscle SOL soleus muscle p<.5 compared to age-matched young Achilles tendon stiffness -14% -21% MG pennation angle SOL pennation angle -14% Achilles tendon stiffness MG pennation angle SOL pennation angle Stenroth L., Gapeyeva H., Pääsuke M. et al. et al. J Gerontol A Biol Sci Med Sci 215;7: Gender differences in Achilles tendon stiffness and triceps surae muscle pennation angle in older adults Stiffness (N/mm) Achilles tendon stiffness -25% Angle ( ) Pennation angle -2% 4 5 MG MG pennation angle SOL SOL pennation angle p<.5 MG medial gastrocnemius muscle SOL soleus muscle Stenroth L., Gapeyeva H., Pääsuke M. et al. et al. J Gerontol A Biol Sci Med Sci 215;7:

8 Difference (%) Lower extremity motor performance Differences compared to gender-matched young -35% -38% 23% 24% Quadriceps torque Timed Up and Go test -18% -24% Walking speed QF quadriceps femoris muscle; 6MWT- 6 min Walk Test p<.5 compared with age-matched young Sillanpää E., Gapeyeva H., Pääsuke M. et. Age, 214, 36: 9667 Bijlsma A.Y., Gapeyeva H., Pääsuke M. et. Osteporos Int, 213, 24: Torque (Nm) Time (s) Walking speed (m/s) Gender differences in older -37% Timed Up and GO test -8% Walking speed QF strength p<.5 3 m p<.5 6MWT Average speed Regressionanalysis demonstrated a significant positive association ofserumconcentrationofigf-1 withquadriceps femoris muscle torque in older men but not in older women Group Β coefficient(95% CI) p value OM.67 (.7 to 1.26).29 OW.2 (-.37 to.41).912 Adjusted for age, gender, z score of fat mass percentage height and country. Log-transformed data. p<.5 Serum concentration of IGF-1 (mean ± SD): OM = 82. ± 51.5 ng/ml; YM = ± 82.1; p<.1 OW = 83.3 ± 41.9 ng/ml; YW = ± 85.3; p<.1 Bucci L, Seppet E, Gapeyeva H, Pääsuke M et al. Biogerontology, 213, 14:

9 Mobility associated with Achilles tendon stiffness and parameters on triceps surae muscle architecture in older adults r =.52, p<.1 r =.48, p<.1 r = -.29, p<.5 Ultrasonography r = -.43, p<.1 r =.3, p<.5 Muscle fascicle length Subjects: 7-81 yrs; n=52; 5% women TUG Timed Up and Go test 6mwt 6 min walk test Stenroth L., Gapeyeva H., Pääsuke M. et al. et al. J Gerontol A Biol Sci Med Sci 215;7: Age-related changes in plasma concentration of the circulating markers of bone remodelling % Difference comparet to young % 14% 47% 43% 5% 32% -19% -4% DISKOPF-1 SCEROSTIN OSTEOPONTIN OSTEOCALCIN OSTEOPROTEGRIN Diskopf-1 Sclerostin Osteopontin Osteocalcin Osteoprotegrin Bone resorption markers Bone formation markers p<.5 compared to gender-matched young Coulson J, Gapeyeva H, Pääsuke M et al. Osteopor Int, 217, 28:

10 Gender differences in plasma concentrations of circulating markers of bone remodelling in older adults 3 6 Concentration (pg/ml) % Concentration (pg/ml) % 5-27% 1 Sclerostin Osteopontin Osteocalcin Diskopf-1 Osteoprotegrin Data are median ± 25th-75th percentiles p<.5 compared to age-matched men Coulson J, Gapeyeva H, Pääsuke M et al. Osteopor Int, 217, 28: Bone turnover and circulating markers of bone remodelling Fascilitation of bone formation: Osteocalcin released from the bone matrix during bone resorption Reduction of bone resorption: Osteoprotegrin expressed by osteocytes and osteoblasts, can reduce production of osteoclasts Fascilitation of bone resorption: Osteopontin released by osteoblasts, osteocytes and osteoclasts Reduction of bone formation: Diskopf-related protein 1 released by osteocytes, major non-collagen protein in matrix Sclerostin released by osteocytes Shetty S et al. Indian J Endogrinol Metab, 216, 2:

11 Associations between circulating bone regulatory factors and WBMD in older adults Parameter r p Diskopf-1 (pg/ml) Sclerostin (pg/ml) Osteopontin (pg/ml) Osteocalcin (pg/ml) Osteoprotegerin (pg/ml) p< Data are shown as Spearman`s rho. The circulatory bone regulatory factors were logtransformed and their z-scores calculated WBMD whole body bone mineral density p<.5 Bone resorption markers Bone formation markers Coulson J, Gapeyeva H, Pääsuke M et al. Osteopor Int, 217, 28: CONCLUSIONS Healthy older men and women in this cross-sectional study exhibited significant gender differences in body composition, lower extremity motor performance and blood biomarkers. As compared to age-matched men, older women had: general adiposity; lean body mass, ASM, WBMC and WBMD; Achilles tendon stiffness and soleus muscle pennation angle; QF muscle strength; plasma concentrations of sclerostin, osteopontin and osteoprotegrin. This study demonstrated common and gender-specific associations between different diagnostic parameters of sarcopenia and WBMD in older adults. Positively associated in older men and women: WBMD body mass and body mass components (body fat mass and lean body mass), ASM index, plasma concentrations of discopf-1, sclerostin, osteocalcin and osteoprotegrin. walking speed Achillis tendon stiffness and plantarflexor muscle strength. Positively associated in older men only: QF muscle strength WBMD and serum concentration of IGF-1 11

12 Acknowledgement This study was supported by: European Union FP7 project MYOAGE Estonian Science Foundation grant No 7823 Estonian Science Foundation grant No 8736 MAIN COLLABORATORS Laboratory of Kinesiology and Biomechanics, UNI Tartu Gillian Butler-Browne UNI Paris 6, INSERM, France Project Principal Enn Seppet UNI Tartu, Estonia Andrea B Maier UNI Leiden, The Netherlands Jean-Yves Hogrel Institute of Myology, Paris, France From left: Jaan Ereline Helena Gapeyeva Tatjana Kums Mati Pääsuke Sarianna Sipilä UNI Jyväskylä, Finland Jamie McPhee UNI Manchester Metropolitan, UK 12

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