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Montiel Rojas, D., Nilsson, A., Ponsot, E., Brummer, R. J., Fairweather-Tait, S., Jennings, A., . . . Kadi, F. (2018). Short Telomere Length Is Related to Limitations in Physical Function in Elderly European Adults. Frontiers in Physiology, 9, Article ID 1110.
Open this publication in new window or tab >>Short Telomere Length Is Related to Limitations in Physical Function in Elderly European Adults
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2018 (English)In: Frontiers in Physiology, ISSN 1664-042X, E-ISSN 1664-042X, Vol. 9, article id 1110Article in journal (Refereed) Published
Abstract [en]

The present study aims to explore the potential influence of leucocyte telomere length (LTL) on both a single indicator and a composite construct of physical functioning in a large European population of elderly men and women across diverse geographical locations. A total of 1,221 adults (65-79 years) were recruited from five European countries within the framework of NU-AGE study. The physical functioning construct was based on the 36-item Short Form Health Survey. Handgrip strength was used as a single indicator of muscle function and LTL was assessed using quantitative real-time PCR. Women had significantly longer (p < 0.05) LTL than men. Participants in Poland had significantly shorter LTL than in the other study centers, whereas participants in the Netherlands had significantly longer LTL than most of the other centers (p < 0.01). An analysis of LTL as a continuous outcome against physical functioning by using linear models revealed inconsistent findings. In contrast, based on an analysis of contrasting telomere lengths (first vs. fifth quintile of LTL), a significant odds ratio (OR) of 1.7 (95% CI: 1.1 -2.6; p < 0.05) of having functional limitation was observed in those belonging to the first LTL quintile compared to the fifth. Interestingly, having the shortest LTL was still related to a higher likelihood of having physical limitation when compared to all remaining quintiles (OR: 1.5, 95% CI: 1.1 -2.1; p < 0.05), even after adjustment by study center, age, sex, and overweight status. Collectively, our findings suggest that short LTL is an independent risk factor that accounts for functional decline in elderly European populations. The influence of LTL on functional limitation seems driven by the detrimental effect of having short telomeres rather than reflecting a linear dose-response relationship.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018
Keywords
aging, ethnicity, handgrip strength, SF-36, physical function
National Category
Physiology
Identifiers
urn:nbn:se:oru:diva-68587 (URN)10.3389/fphys.2018.01110 (DOI)000441323300001 ()2-s2.0-85051645979 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme, 266486
Available from: 2018-08-27 Created: 2018-08-27 Last updated: 2018-09-14Bibliographically approved
Särnblad, S., Ponsot, E. & Kadi, F. (2017). Acute effects on glycemia of different types of exercise in youths with type 1 diabetes. In: : . Paper presented at ISPAD 2017, Innsbruck, Austria, October 18-21, 2017.
Open this publication in new window or tab >>Acute effects on glycemia of different types of exercise in youths with type 1 diabetes
2017 (English)Conference paper, Poster (with or without abstract) (Refereed)
National Category
Pediatrics
Research subject
Pediatrics
Identifiers
urn:nbn:se:oru:diva-61856 (URN)
Conference
ISPAD 2017, Innsbruck, Austria, October 18-21, 2017
Available from: 2017-10-18 Created: 2017-10-18 Last updated: 2017-11-01Bibliographically approved
Sillanpää, E., Niskala, P., Laakkonen, E. K., Ponsot, E., Alén, M., Kaprio, J., . . . Sipilä, S. (2017). Leukocyte and Skeletal Muscle Telomere Length and Body Composition in Monozygotic Twin Pairs Discordant for Long-term Hormone Replacement Therapy. Twin Research and Human Genetics, 20(2), 119-131
Open this publication in new window or tab >>Leukocyte and Skeletal Muscle Telomere Length and Body Composition in Monozygotic Twin Pairs Discordant for Long-term Hormone Replacement Therapy
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2017 (English)In: Twin Research and Human Genetics, ISSN 1832-4274, E-ISSN 1839-2628, Vol. 20, no 2, p. 119-131Article in journal (Refereed) Published
Abstract [en]

Estrogen-based hormone replacement therapy (HRT) may be associated with deceleration of cellular aging. We investigated whether long-term HRT has effects on leukocyte (LTL) or mean and minimum skeletal muscle telomere length (SMTL) in a design that controls for genotype and childhood environment. Associations between telomeres, body composition, and physical performance were also examined. Eleven monozygotic twin pairs (age 57.6 ± 1.8 years) discordant for HRT were studied. Mean duration of HRT use was 7.3 ± 3.7 years in the user sister, while their co-twins had never used HRT. LTL was measured by qPCR and SMTLs by southern blot. Body and muscle composition were estimated by bioimpedance and computed tomography, respectively. Physical performance was measured by jumping height and grip strength. HRT users and non-users did not differ in LTL or mean or minimum SMTL. Within-pair correlations were high in LTL (r = 0.69, p = .020) and in mean (r = 0.74, p = .014) and minimum SMTL (r = 0.88, p = .001). Body composition and performance were better in users than non-users. In analyses of individuals, LTL was associated with BMI (r 2 = 0.30, p = .030), percentage total body (r 2 = 0.43, p = .014), and thigh (r 2 = 0.55, p = .004) fat, while minimum SMTL was associated with fat-free mass (r 2 = 0.27, p = .020) and thigh muscle area (r 2 = 0.42, p = .016). We found no associations between HRT use and telomere length. Longer LTLs were associated with lower total and regional fat, while longer minimum SMTLs were associated with higher fat-free mass and greater thigh muscle area. This suggests that telomeres measured from different tissues may have different associations with measures of body composition.

Place, publisher, year, edition, pages
Cambridge, United Kingdom: Cambridge University Press, 2017
Keywords
Estrogen, telomeres, percentage of fat, fat-free mass, computed tomography, bioimpedance, twin design, post-menopausal
National Category
Medical Genetics Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:oru:diva-55958 (URN)10.1017/thg.2017.1 (DOI)000398563000003 ()28193312 (PubMedID)2-s2.0-85012257856 (Scopus ID)
Note

Funding Agencies:

EC FP7 Collaborative Project MYOAGE  GA-223576

Academy of Finland  265240  263278

Finnish Ministry of Culture and Education  251316  89/672/2008

Post doc research grant from the Academy of Finland  260001

Available from: 2017-03-10 Created: 2017-03-10 Last updated: 2018-01-13Bibliographically approved
Mackey, A. L., Rasmussen, L. K., Kadi, F., Schjerling, P., Helmark, I. C., Ponsot, E., . . . Kjaer, M. (2016). Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication. The FASEB Journal, 30(6), 2266-2281
Open this publication in new window or tab >>Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication
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2016 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 30, no 6, p. 2266-2281Article in journal (Refereed) Published
Abstract [en]

With this study we investigated the role of nonsteroidal anti-inflammatory drugs (NSAIDs) in human skeletal muscle regeneration. Young men ingested NSAID [1200 mg/d ibuprofen (IBU)] or placebo (PLA) daily for 2 wk before and 4 wk after an electrical stimulation-induced injury to the leg extensor muscles of one leg. Muscle biopsies were collected from the vastus lateralis muscles before and after stimulation (2.5 h and 2, 7, and 30 d) and were assessed for satellite cells and regeneration by immunohistochemistry and real-time RT-PCR, and we also measured telomere length. After injury, and compared with PLA, IBU was found to augment the proportion of ActiveNotch1(+) satellite cells at 2 d [IBU, 29 ± 3% vs. PLA, 19 ± 2% (means ± sem)], satellite cell content at 7 d [IBU, 0.16 ± 0.01 vs. PLA, 0.12 ± 0.01 (Pax7(+) cells/fiber)], and to expedite muscle repair at 30 d. The PLA group displayed a greater proportion of embryonic myosin(+) fibers and a residual ∼2-fold increase in mRNA levels of matrix proteins (all P < 0.05). Endomysial collagen was also elevated with PLA at 30 d. Minimum telomere length shortening was not observed. In conclusion, ingestion of NSAID has a potentiating effect on Notch activation of satellite cells and muscle remodeling during large-scale regeneration of injured human skeletal muscle.-Mackey, A. L., Rasmussen, L. K., Kadi, F., Schjerling, P., Helmark, I. C., Ponsot, E., Aagaard, P., Durigan, J. L. Q., Kjaer, M. Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti-inflammatory medication.

Place, publisher, year, edition, pages
Bethesda, USA: Federation of American Societies for Experimental Biology, 2016
Keywords
Pax7, electrical stimulation, telomere length, extracellular matrix, Notch signaling pathway
National Category
Physiology Cell and Molecular Biology
Research subject
Molecular Biology
Identifiers
urn:nbn:se:oru:diva-49204 (URN)10.1096/fj.201500198R (DOI)000376878300018 ()26936358 (PubMedID)2-s2.0-84971654983 (Scopus ID)
Note

Funding Agencies:

U.S. National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development

Nordea Foundation 223576

European Commission

Danish Rheumatism Association

Team Danmark

Anti Doping Danmark

Oster-Jorgensen og Romhild Andersen Fonden

King Christian IX and Queen Louise's Anniversary grant (Kong Christian IX og Dronning Louises Jubilaeumslegat)

Danish Agency for Science Technology and Innovation (Medical Research Council)

Lundbeck Foundation

Available from: 2016-03-11 Created: 2016-03-10 Last updated: 2018-01-10Bibliographically approved
Leprêtre, P. M., Ponsot, E., Särnblad, S. & Kadi, F. (2016). Cardiorespiratory responses to incremental exercise in Type 1 diabetic patients: a comparison between patients with poor and good glycaemia control. In: : . Paper presented at 26ièmes Journées Européennes de la Société Française de Cardiologie, Paris, France, 13-16 jan., 2016.
Open this publication in new window or tab >>Cardiorespiratory responses to incremental exercise in Type 1 diabetic patients: a comparison between patients with poor and good glycaemia control
2016 (English)Conference paper, Poster (with or without abstract) (Refereed)
Keywords
Diabetes
National Category
Medical and Health Sciences Endocrinology and Diabetes
Research subject
Pediatrics
Identifiers
urn:nbn:se:oru:diva-53314 (URN)
Conference
26ièmes Journées Européennes de la Société Française de Cardiologie, Paris, France, 13-16 jan., 2016
Available from: 2016-10-28 Created: 2016-10-28 Last updated: 2017-10-18Bibliographically approved
Bankole, L.-C., Millet, G. Y., Temesi, J., Bachasson, D., Ravelojaona, M., Wuyam, B., . . . Feasson, L. (2016). Safety and efficacy of a 6-month home-based exercise program in patients with facioscapulohumeral muscular dystrophy A randomized controlled trial. Medicine (Baltimore, Md.), 95(31), Article ID e4497.
Open this publication in new window or tab >>Safety and efficacy of a 6-month home-based exercise program in patients with facioscapulohumeral muscular dystrophy A randomized controlled trial
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2016 (English)In: Medicine (Baltimore, Md.), ISSN 0025-7974, E-ISSN 1536-5964, Vol. 95, no 31, article id e4497Article in journal (Refereed) Published
Abstract [en]

Background: Previous randomized controlled trials investigating exercise training programs in facioscapulohumeral muscular dystrophy (FSHD) patients are scarce and of short duration only. This study assessed the safety and efficacy of a 6-month home-ased exercise training program on fitness, muscle, and motor function in FSHD patients.

Methods: Sixteen FSHD patients were randomly assigned to training (TG) and control (CG) groups (both n=8) in a home-based exercise intervention. Training consisted of cycling 3 times weekly for 35minutes (combination of strength, high-intensity interval, and low-intensity aerobic) at home for 24 weeks. Patients in CG also performed an identical training program (CTG) after 24 weeks. The primary outcome was change in peak oxygen uptake (VO2 peak) measured every 6 weeks. The principal secondary outcomes were maximal quadriceps strength (MVC) and local quadriceps endurance every 12 weeks. Other outcome measures included maximal aerobic power (MAP) and experienced fatigue every 6 weeks, 6-minute walking distance every 12 weeks, and muscle characteristics from vastus lateralis biopsies taken pre- and postintervention.

Results: The compliance rate was 91% in TG. Significant improvements with training were observed in the VO2 peak (+19%, P= 0.002) and MAP by week 6 and further to week 24. Muscle endurance, MVC, and 6-minute walking distance increased and experienced fatigue decreased. Muscle fiber cross-sectional area and citrate synthase activity increased by 34% (P=0.008) and 46% (P=0.003), respectively. Dystrophic pathophysiologic patterns were not exacerbated. Similar improvements were experienced by TG and CTG.

Conclusions: A combined strength and interval cycling exercise-training program compatible with patients' daily professional and social activities leads to significant functional benefits without compromising muscle tissue.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2016
Keywords
combined strength and endurance training, exercise training, facioscapulohumeral muscular dystrophy, home-based, myopathy, randomized controlled trial
National Category
General Practice
Research subject
Family Medicine
Identifiers
urn:nbn:se:oru:diva-52151 (URN)10.1097/MD.0000000000004497 (DOI)000380789800083 ()27495097 (PubMedID)2-s2.0-84983250815 (Scopus ID)
Note

Funding Agencies:

Association Francaise contra la Myopathie (AFM)

Örebro University

Rhone-Alpes Region

Available from: 2016-09-14 Created: 2016-09-14 Last updated: 2018-07-16Bibliographically approved
Strandberg, E., Edholm, P., Ponsot, E., Wåhlin-Larsson, B., Hellmén, E., Nilsson, A., . . . Kadi, F. (2015). Influence of combined resistance training and healthy diet on muscle mass in healthy elderly women: a randomized controlled trial. Journal of applied physiology, 119(8), 918-925
Open this publication in new window or tab >>Influence of combined resistance training and healthy diet on muscle mass in healthy elderly women: a randomized controlled trial
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2015 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 119, no 8, p. 918-925Article in journal (Refereed) Published
Abstract [en]

The delivery of efficient nonpharmacological treatment to prevent the loss of muscle mass in older adults is a major challenge, and information on the combined effects of training and diet is particularly important. Here we aimed to evaluate the effects of 24 wk of resistance training combined with a healthy dietary approach (n-6/n-3 ratio < 2) in a population of healthy and physically active older women (65-70 years). The three-armed randomized controlled trial included a resistance training + healthy diet group (RT-HD), a resistance training group (RT), and controls (CON). All subjects included in the study were physically active and had low levels of serum inflammatory markers. In accordance with the dietary goals, the n-6/n-3 ratio dietary intake significantly decreased only in RT-HD by 42%. An increase in 1 repetition maximum in leg extension occurred in RT (+20.4%) and RT-HD (+20.8%), but not in CON. Interestingly, leg lean mass significantly increased only in RT-HD (+1.8%). While there were no changes in serum C-reactive protein and IL-6 levels, a significant decrease in serum level of the pro-inflammatory precursor arachidonic acid (-5.3 +/- 9.4%) together with an increase in serum n-3 docosahexaenoic acid (+8.3%) occurred only in RT-HD. Altogether, this study demonstrates that the effects of resistance training on muscle mass in healthy older adults can be optimized by the adoption of a healthy diet.

Place, publisher, year, edition, pages
American Physiological Society, 2015
Keywords
aging, C-reactive protein, exercise, fatty acids, inflammation, skeletal muscle
National Category
Sport and Fitness Sciences Physiology
Research subject
Physiology
Identifiers
urn:nbn:se:oru:diva-46442 (URN)10.1152/japplphysiol.00066.2015 (DOI)000362959800009 ()26338453 (PubMedID)2-s2.0-84946046698 (Scopus ID)
Note

Funding Agency:

Swedish National Center for Research in Sports P2012/0102 P2014-0117

Available from: 2015-11-10 Created: 2015-11-10 Last updated: 2018-09-14Bibliographically approved
Marklund, P., Mattsson, C. M., Wåhlin-Larsson, B., Ponsot, E., Lindvall, B., Lindvall, L., . . . Kadi, F. (2013). Extensive inflammatory cell infiltration in human skeletal muscle in response to an ultraendurance exercise bout in experienced athletes. Journal of applied physiology, 114(1), 66-72
Open this publication in new window or tab >>Extensive inflammatory cell infiltration in human skeletal muscle in response to an ultraendurance exercise bout in experienced athletes
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2013 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 114, no 1, p. 66-72Article in journal (Refereed) Published
Abstract [en]

The impact of a 24-h ultraendurance exercise bout on systemic and local muscle inflammatory reactions was investigated in nine experienced athletes. Blood and muscle biopsies were collected before (Pre), immediately after the exercise bout (Post), and after 28 h of recovery (Post28). Circulating blood levels of leukocytes, creatine kinase (CK), C-reactive protein (CRP), and selected inflammatory cytokines were assessed together with the evaluation of the occurrence of inflammatory cells (CD3(+), CD8(+), CD68(+)) and the expression of major histocompatibility complex class I (MHC class I) in skeletal muscle. An extensive inflammatory cell infiltration occurred in all athletes, and the number of CD3(+), CD8(+), and CD68(+) cells were two- to threefold higher at Post28 compared with Pre (P < 0.05). The inflammatory cell infiltration was associated with a significant increase in the expression of MHC class I in muscle fibers. There was a significant increase in blood leukocyte count, IL-6, IL-8, CRP, and CK at Post. At Post28, total leukocytes, IL-6, and CK had declined, whereas IL-8 and CRP continued to increase. Increases in IL-1β and TNF-α were not significant. There were no significant associations between the magnitude of the systemic and local muscle inflammatory reactions. Signs of muscle degenerative and regenerative events were observed in all athletes with various degrees of severity and were not affected by the 24-h ultraendurance exercise bout. In conclusion, a low-intensity but very prolonged single-endurance exercise bout can generate a strong inflammatory cell infiltration in skeletal muscle of well-trained experienced ultraendurance athletes, and the amplitude of the local reaction is not proportional to the systemic inflammatory response.

National Category
Medical and Health Sciences Sport and Fitness Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-31995 (URN)10.1152/japplphysiol.01538.2011 (DOI)000313051000009 ()23104690 (PubMedID)2-s2.0-84871782629 (Scopus ID)
Available from: 2013-10-14 Created: 2013-10-14 Last updated: 2017-12-06Bibliographically approved
Bankole, L.-C., Feasson, L., Ponsot, E. & Kadi, F. (2013). Fibre type-specific satellite cell content in two models of muscle disease. Histopathology, 63(6), 826-832
Open this publication in new window or tab >>Fibre type-specific satellite cell content in two models of muscle disease
2013 (English)In: Histopathology, ISSN 0309-0167, E-ISSN 1365-2559, Vol. 63, no 6, p. 826-832Article in journal (Refereed) Published
Abstract [en]

Aims: Muscle satellite cells (SCs) are responsible for the regenerative events following muscle fibre injury. This study aimed to improve our understanding of SC behaviour in two models of muscle disorder with different pathological mechanisms and onset of disease.

Methods and results: Pax7(+)SC content was assessed in types I and II fibres of patients with Duchenne muscular dystrophy (DMD; n=9; age 132years), polymyositis/dermatomyositis (PM/DM; n=9; age 52 +/- 12years) and in controls (n=5; age 26 +/- 5years). Pax7(+)SCs number in type I and II fibres was higher (P<0.05) in DMD and in PM/DM compared to controls. Type I fibres were associated with a higher number of Pax7(+)SCs compared to type II fibres only in DMD; Pax7(+)SCs number in type I fibres was about threefold higher in DMD compared to PM/DM (P<0.05). In DMD, Pax7(+)SC content in small regenerating fibres (0.09 +/- 0.09 SCs/fibre) was similar to that in fibres from healthy skeletal muscle. The proportion of activated SCs (Ki-67(+)SCs) was fivefold lower in DMD (0.4 +/- 0.4%) compared to PM/DM (2.8 +/- 2%). Pax7(+) cells located outside the basal lamina were observed in DMD muscles only.

Conclusion: The capacity to generate new SCs is increased even in severely impaired muscles and a fibre type-specific enhancement of SC occurs in type I muscle fibres in DMD.

Keywords
Duchenne muscular dystrophy, Pax7, polymyositis and dermatomyositis, regeneration
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:oru:diva-32755 (URN)10.1111/his.12231 (DOI)000327018300009 ()
Note

Funding Agency: French Muscular Dystrophy Association (AFM-Telethon)

Available from: 2013-12-13 Created: 2013-12-13 Last updated: 2017-12-06Bibliographically approved
Ponsot, E., Echaniz-Laguna, A., Delis, A.-M. & Kadi, F. (2012). Telomere length and regulatory proteins in human skeletal muscle with and without ongoing regenerative cycles. Experimental Physiology, 97(6), 774-784
Open this publication in new window or tab >>Telomere length and regulatory proteins in human skeletal muscle with and without ongoing regenerative cycles
2012 (English)In: Experimental Physiology, ISSN 0958-0670, E-ISSN 1469-445X, Vol. 97, no 6, p. 774-784Article in journal (Refereed) Published
Abstract [en]

New insights suggest the existence of telomere regulatory mechanisms in several adult tissues. In this study, we aimed to assess in vivo telomere length and the presence of specific proteins involved in telomere regulation in a model of human skeletal muscle with (patients with dermatomyosis or polymyositis) and without ongoing regenerative events (healthy subjects). Mean (meanTRF) and minimal telomere (miniTRF) lengths and the expression of telomerase, tankyrase 1, TRF2 (telomeric repeat binding factor 2) and POT1 (protection of telomeres 1) were investigated in skeletal muscle samples from 12 patients (MYO) and 13 healthy subjects (CON). There was no significant shortening of telomeres in skeletal muscle from patients compared with control subjects (MYO, meanTRF length 11.0 ± 1.8 kbp and miniTRF length 4.7 ± 0.8 kbp; CON, meanTRF length 10.4 ± 1.1 kbp and miniTRF length 4.6 ± 0.5 kbp). Theoretically, telomere length can be controlled by endogenous mechanisms. Here, we show for the first time that expression levels of telomerase, tankyrase 1, TRF2 and POT1 were, respectively, six-, seven-, three- and fivefold higher in the nuclear fraction of skeletal muscle of MYO compared with CON (P < 0.05). This suggests the existence of endogenous mechanisms allowing for telomere regulation in skeletal muscle with ongoing cycles of degeneration and regeneration and a model where regulatory factors are possibly involved in the protection of skeletal muscle telomeres.

Place, publisher, year, edition, pages
Hoboken, USA: Wiley-Blackwell, 2012
National Category
Basic Medicine Sport and Fitness Sciences
Research subject
Sports Science
Identifiers
urn:nbn:se:oru:diva-24268 (URN)10.1113/expphysiol.2011.063818 (DOI)000305460000010 ()22366562 (PubMedID)2-s2.0-84862604589 (Scopus ID)
Note

Note: Institut national de la santé et de la recherche médicale (INSERM)

Available from: 2012-08-06 Created: 2012-08-06 Last updated: 2018-08-29Bibliographically approved
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