| 1. |
- Harandi, Vahid M., 1985-
(författare)
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A Muscle Perspective on the Pathophysiology of Amyotrophic Lateral Sclerosis : Differences between extraocular and limb muscles
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Amyotrophic lateral sclerosis (ALS) is a late-onset progressive neurodegenerative disorder. ALS has been traditionally believed to be primarily a motor neuron disease. However, accumulating data indicate that loss of contact between the axons and the muscle fibres occurs early; long before the death of motor neurons and that muscle fibres may initiate motor neuron degeneration. Thus, the view of ALS is changing focus from motor neurons alone to also include the muscle fibres and the neuromuscular junctions (NMJs). While skeletal muscles are affected in ALS, oculomotor disturbances are not dominant features of this disease and extraocular muscles (EOMs) are far less affected than limb muscles. Why oculomotor neurons and EOMs are capable to be more resistant in the pathogenetic process of ALS is still unknown.The overall goal of this thesis is to explore the pathophysiology of ALS from a muscle perspective and in particular study the expression and distribution of key neurotrophic factors (NTFs) and Wnt proteins in EOMs and limb muscles from ALS donors and from SOD1G93A transgenic mice. Comparisons were made with age-matched controls to distinguish between changes related to ALS and to ageing.Results: Brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4) were present in EOMs and limb muscles at both mRNA and protein levels in control mice. The mRNA levels of BDNF, NT-3 and NT-4 were significantly lower in EOMs than in limb muscles of early and/or late control mice, indicating an intrinsic difference in NTFs expression between EOMs and limb muscles. qRT-PCR analysis showed significantly upregulated mRNA levels of NT-3 and GDNF in EOMs but significantly downregulated mRNA levels of NT-4 in limb muscles from SOD1G93A transgenic mice at early stage. The NTFs were detected immunohistochemically in NMJs, nerve axons and muscle fibres. The expression of BDNF, GDNF and NT-4 on NMJs of limb muscles, but not of EOMs, was significantly decreased in terminal stage ALS animals as compared to the limb muscles of the age-matched controls. In contrast, NTFs expression in intramuscular nerve axons did not present significant changes in either muscle group of early or late ALS mice. NTFs, especially BDNF and NT-4 were upregulated in some small-sized muscle fibres in limb muscles of late stage ALS mice. All the four Wnt isoforms, Wnt1, Wnt3a, Wnt5a and Wnt7a were detected in most axon profiles in all human EOMs with ALS, whereas significantly fewer axon profiles were positive in the human limb muscles except for Wnt5a. Similar differential patterns were found in myofibres, except for Wnt7a, where its expression was elevated within sarcolemma of limb muscle fibres. β-catenin, a marker of the canonical Wnt pathway was activated in a subset of myofibres in the EOMs and limb muscle in all ALS patients. In the SOD1G93A mouse, all four Wnt isoforms were significantly decreased in the NMJs at the terminal stage compared to age matched controls.Conclusions: There were clear differences in NTF and Wnt expression patterns between EOM and limb muscle, suggesting that they may play a role in the distinct susceptibility of these two muscle groups to ALS. In particular, the early upregulation of GDNF and NT-3 in the EOMs might play a role in the preservation of the EOMs in ALS. Further studies are needed to determine whether these proteins and the pathways they control may be have a future potential as protecting agents for other muscles.
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| 2. |
- Montiel Rojas, Diego, 1984-
(författare)
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Diet and sarcopenia risk in community-dwelling older European adults
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The age-related decline in muscle strength and muscle mass can lead to sarcopenia with higher risk of falls, disability, and loss of independence. In this context, healthy dietary habits have the potential to delay onset of physical limitations, thereby promoting healthy ageing. The overall aim of the thesis was to investigate the role of dietary habits on indicators ofmuscle health in a sample of community-dwelling older European men and women. The studies were performed within the frame of the NU-AGE project, a multi-centre study aiming to determine the impact of dietary habits on age-related functional decline. Studies I-III were based on crosssectional analyses, whereas study IV was a randomised controlled trial (RCT). In summary, Study I highlighted the independent roles of dietary protein amount and quality for muscle health in older adults. A positive linear dose-response relationship existed between protein intake and muscle health, with increased intake of plant-based proteins to the detriment of animal-based proteins was associated with reduced sarcopenia risk. Study II revealed that increased poly-unsaturated fatty acids intake to the detriment of saturated fatty acids was associated with lower sarcopenia risk in older adults with a dietary protein intake below 1.1 g/kg of body weight. In Study III, beneficial links between dietary fibre intake and muscle mass were observed in older European adults. In Study IV, a one-year RCT promoting adherence to a Mediterranean-style diet did not result in significant changes in muscle strength or mass. In conclusion, the present dissertation emphasised the important potential of macronutrient amount and quality in the prevention of age-related loss of muscle strength and muscle mass. However, future experimental studies are warranted to clarify the impact of whole-diet approaches, such as the Mediterranean diet, on the maintenance of muscle health in older adults.
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| 3. |
- Bergens, Oscar, 1991-
(författare)
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Chronic Systemic Inflammation, Body Composition and Physical Activity Behaviours in Older Adults
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ageing is associated with a gradual physical decline accompanied by changes in body composition. The occurrence of a low-grade yet chronic state of systemic inflammation has gained interest for its potential consequences in the ageing process. Importantly, a physically active lifestyle may promote the maintenance of muscle mass, reduction in adipose tissue, and alleviate progression of a chronic pro-inflammatory state. The overall aim of this thesis was to explore relationships between biomarkers of systemic inflammation, body composition, and physical activity behaviours in community-dwelling older adults aged 65 to 70 years.A main finding of the thesis is the existence of associations between body composition and systemic inflammation in older adults, where excess adipose tissue is adversely associated with levels of inflammatory biomarkers in older women. Inverse associations were also observed between muscle mass and levels of pro-inflammatory biomarkers in older women. This thesis also highlights sex-specific associations between systemic inflammation and physical activity behaviours. Longer time spent sedentary was also associated with higher levels of proinflammatory biomarkers in older women and lower level of antiinflammatory biomarkers in older men. Reallocating time spent in activities of lower intensities with higher intensities was associated with lower levels of pro-inflammatory biomarkers in older women. Overall, the findings of this thesis support efforts promoting physical activity at the expense of sedentary time in order to combat age-related systemic inflammation and metabolic risk in older adults.
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| 4. |
- Edholm, Peter, 1977-
(författare)
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Muscle mass and physical function in ageing : the effects of physical activity and healthy diet
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ageing is associated with a gradual deterioration in physical function, accompanied by a decrease in muscle mass, leading to loss of independency. In this respect, physical activity and healthy diet represent key lifestyle factors with potential to delay onset of age-related physical disability. The overall aim of the present thesis was to explore the effects of physical activity behaviours in general and resistance training (RT) in particular, with or without addition of a healthy diet (HD), on muscle mass and physical function in older community-dwelling women. A main finding was that physical activity of at least moderate intensity at old age infers beneficial effects on physical function, even in individuals with a previously sedentary lifestyle. Additionally, engagement in exercise-related activities during middleage years is linked to better physical function and higher muscle massat old age, regardless of present physical activity level. This thesis further highlights that in older women RT combined with HD rich in omega-3 polyunsaturated fatty acids elicits significant gains in muscle mass, whereas no corresponding gain was induced by RT alone. Likewise, larger improvements in muscle strength and physical function were evident in response to combined effects by RT and HD compared to RT alone. Taken together, findings from this thesis support public health efforts aiming to promote physical activity of at least moderate intensity together with a healthy diet rich in omega-3 polyunsaturated fatty acids in order to combat age-related decline in muscle mass and physical function.
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| 5. |
- Song, Yafeng, 1977-
(författare)
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Cross transfer effects after unilateral muscle overuse : an experimental animal study about alterations in the morphology and the tachykinin system of muscles
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Unilateral exercise can produce certain contralateral strength effects. Deleterious events can be cross-transferred as well, as illustrated by a strict symmetry in some chronic inflammatory diseases. To date, knowledge on the effects of marked overuse of skeletal muscles is limited, and there is largely no information if unilateral overuse affects the contralateral muscles. In view of this, the present study was undertaken to test the hypothesis that unilateral muscle overuse causes alterations in tissue structure and the tachykinin system, with a focus on substance P (SP), not only in the exercised muscles, but also in the contralateral muscles. SP is a well-known neuromodulator that is known to be proinflammatory.An experimental rabbit model with unilateral muscle overuse of the soleus and gastrocnemius muscles caused by exercise via electrical muscle stimulation (E/EMS) was used. In total, 40 rabbits were randomly divided into seven groups of which two groups served as controls. The rabbits were anaesthetized and then set on a “kicking machine” to perform exercise via EMS for 2h every second day. Experimental periods for groups 1-3 were 1, 3 and 6w, respectively, whereas groups 4-6 were exercised for 1w but also subjected to injections in the peritendinous tissue with SP, NaCL, Captopril (C), an ACE inhibitor, and DL-Thiorphan (Th) which inhibits the activity of neural endopeptidase. One group was not subjected to the experiment at all. The day after the last session of E/EMS, the soleus muscle and the gastrocnemius muscle from both legs were collected for analysis. Alterations in muscle structure and the tachykinin system were analyzed with enzyme and immunohistochemical techniques, in situ hybridization and EIA methods.After 1w of E/EMS, focal areas of the exercised muscles contained a mild infiltration of inflammatory cells (myositis) and small morphological changes. After 3 and 6w of E/EMS, distinct myositis and muscle changes were bilaterally present in focal areas of both muscles. The structural changes, which mainly were observed in myositis areas, consisted of increased fiber size variability, split fibers, internal myonuclei, necrotic fibers, fibrosis, fat infiltration, and small fibers containing developmental MyHCs. Bilateral morphological changes, such as loss of axons, were also observed in nerves. In addition, expressions of tachykinin and the SP-preferred receptor, the neurokinin-1 (NK-1R), were bilaterally upregulated in nerve structures and blood vessel walls. Infiltrating white blood cells exhibited tachykinin–like and NK-1R immunoreactivity. NK-1R immunoreactions were also found in necrotic and regenerating muscle fibers.The concentration of tachykinin (SP) was significantly increased in both soleus and gastrocnemius muscles after E/EMS. There was a significant correlation between the two sides in concentration of tachykinin and in the intensity of tachykinin-like immunoreaction in blood vessel walls. The muscle fiber size and capillary supply of fibers were bilaterally decreased after 3w of EMS. The myositis areas contained an increased number of vessels with a larger size than capillaries, while areas with increased amount of connective tissue contained a very low number of capillaries. A bilateral fiber type shift against a lower proportion of slow MyHCI fibers and higher proportion of fast MyHCII fibers was observed in both muscles. The local injections of C+Th and SP+C+Th led to marked structural changes in the muscle tissue and marked increased NK-1R and tachykinin-like immunoreactivity in the myositis areas and increased tachykinin concentration in the tissue.In conclusion, the repetitive unilateral muscle overuse caused by E/EMS led overtime to muscle injury and myositis. The affected areas contained both degenerative and regenerative alterations in the muscle tissue and nerves, and an upregulation of the tachykinin system. Most interestingly, the changes not only occurred in the exercised side, but also in the homologous contralateral muscles. The tachykinin system appears to be an important factor in the processes of crossover effects.
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| 6. |
- Strandberg, Emelie, 1986-
(författare)
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Skeletal Muscle Mass & Function in Older Women : Health-Enhancing Influences of Combined Resistance Exercise & Diet
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ageing is accompanied by a progressive decline in skeletal muscle mass and strength which may lead to impaired ability to perform activities of daily living in older adults. Although the exact cause of the gradual decline in muscle mass is unknown, identifying efficient strategies aiming to prevent age-related loss of muscle mass and strength is important in order to promote healthy ageing. The overall aim of this thesis was to explore the effects of resistance training alone or combined with a healthy diet on skeletal muscle mass and function of healthy recreationally active older women and to determine mechanisms by which elevated systemic inflammation may contribute to the age-related decline of muscle mass in older adults. The combination of resistance training and a healthy diet induced gains in leg lean mass as well as greater gains in dynamic explosive force than resistance training alone in healthy recreationally active older women. The observed gains in leg lean mass were accompanied by increases in the size of type IIA muscle fibres together with down-regulation in gene expression of a pro-inflammatory factor (IL-1β) and upregulation in gene expression of a regulator of cellular growth (mTOR) in skeletal muscle of older women. Additionally, reduced muscle protein synthesis and size of muscle cells may mediate the detrimental effects of elevated circulating markers of inflammation on muscle mass in older adults. In conclusion, the present thesis depicts mechanistic links between elevated systemic marker of inflammation and muscle mass and provides new information on the effects of combined resistance training and healthy diet on muscle mass and strength in a group of healthy recreationally active older women. This knowledge is instrumental for development of strategies aiming to prevent age-related loss of muscle mass and function.
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| 7. |
- Wåhlin Larsson, Britta, 1959-
(författare)
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Skeletal muscle in Restless legs syndrome (RLS) and Obstructive sleep apnoea syndrome (OSAS)
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Restless legs syndrome (RLS) and Obstructive sleep apnoea syndrome (OSAS) are two sleep disorders that affect daily life with symptoms such as sleepiness and fatigue. It was therefore hypothesised that the skeletal muscle could be affected as symptoms from skeletal muscle are common. The overall aim of the thesis was to investigate aerobic capacity and structure of skeletal muscle in patients with OSAS and RLS and an age matched control group to provide information regarding the underlying mechanisms. The specific aims were to investigate muscle fibre composition, capillary network, capillary proliferation and sings of local inflammation in musculus tibialis anterior of RLS and OSAS.OSAS and RLS patients had a significantly lower predicted VO2 max expressed in ml/min/kg compared with the control group and in the OSAS group apnoes-hyponea index (AHI) was inversely correlated to maximal oxygen uptake Fibre type composition and muscle fibre cross sectional area in the tibialis anterior muscle was equal in all groups with a predominant proportion of slow type I fibres and a smaller fibre area in slow type I fibres compared to fast type II fibres. The distribution of fast fibres (I/IIA, IIA) did not differ except for the group IIX and IIA/IIX where OSAS and RLS had a significantly higher percentage. OSAS patients had a significantly higher number of capillaries per fibre (CAF) for slow type I fibres and CAF per fibre area (CAFA) for fast type II fibres. CFPE- index (capillary to fibre perimeter exchange) and LC/PF-index (length of capillary/perimeter of fibre) were higher in both patient groups. Vascular endothelial growth factor (VEGF) and proliferating endothelial cells were analysed by double-immunofluorescence staining and were presented to a greater extent in the patient groups compared with the healthy controls. Based on normal amounts of T-cells and macrophages in the histological picture it was also demonstrated that local inflammation was not present in the tibialis anterior muscle of RLS and OSAS whish was also supported by the absence of expression of major histocompatibility complex class I molecules (MHC class I) on the surface of the tibialis anterior muscle fibres.In conclusion, the low predicted VO2 max together with higher percentage of type IIX and IIA/IIX muscle fibres indicates a low central capacity in the patient groups. The increased capillary network and the absence of inflammation indicate the occurrence of local hypoxia in tibialis anterior muscle in patients OSAS and RLS.
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| 8. |
- Andersson, Helena M., 1973-
(författare)
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The physiological impact of soccer on elite female players and the effects of active recovery training
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Female soccer is becoming more popular and professional in the world. There are, however, limited scientific data available on how elite female players respond to physical stress during soccer games. An effective recovery strategy following a game is important, because there are few recovery days between the games in international tournaments. The present thesis, which was designed to mirror a competitive situation, aimed to investigate changes in several physiological systems occurring in female elite players in response to two soccer games. It also aimed to investigate the effects of active recovery training on the recovery of several physiological systems. METHODS: Two elite female soccer teams played two 90-min games separated by 72 h active or passive recovery. The active recovery training (cycling at 60% HRpeak, resistance training at <50% 1RM) lasted one hour and was performed 22 and 46 h after the first game. Countermovement jump (CMJ), 20-m sprint time and isokinetic knee strength were measured before, immediately, 5, 21, 45, 51, and 69 h after the first game, and immediately after the second game. The physical stress markers (CK, urea), oxidative stress markers (e.g., GSSG, lipid peroxidation), endogenous (e.g., UA, thiols) and dietary antioxidants (e.g., tocopherols, carotenoids) and a large battery of cytokines (e.g., IL-6, TNF-α) were analysed in blood. RESULTS: No significant differences were observed in the performance parameters, oxidative stress and antioxidant levels or inflammatory response between the active and passive recovery groups. Sprint and isokinetic knee strength were reduced by the same extent after both games. CMJ decreased after the first game and remained reduced throughout the study period. Blood physical stress markers, GSSG and endogenous antioxidants increased with similar amplitude after both games together with unchanged lipid peroxidation. The dietary antioxidants showed either a rapid and persistent change (e.g., tocopherols) or a delayed rise (carotenoids) after the first game. A transient increase occurred in several pro- (e.g., IL-12, TNF-a, MCP-1), anti-inflammatory (e.g., IL-4, IL-10, INF-a) and mixed (IL-6) cytokines after the first game. Fewer cytokines increased in response to the second game. CONCLUSION: Two repeated elite female soccer games separated by 72 h induced similar acute changes in several physiological parameters. After the first game, differences in the recovery pattern of the neuromuscular parameters occurred. In particular, the slow recovery of CMJ indicates that special attention should be devoted to the training of explosive force. Furthermore, the recruitment of antioxidants in response to the transient increase in GSSG resulted in the maintenance of the redox-balance in female players. Similarly, a strong and balanced pro- and anti-inflammatory cytokine response occurred after one single female soccer game. The consequences of the dampened cytokine response during repeated soccer games are, however, unknown. In general, the majority of the parameters had recovered prior to the second game and the physiological alterations induced by the first game did not affect the performance of players in the second game. Finally, active recovery training conducted after a soccer game does not accelerate the recovery time for neuromuscular, oxidative stress, antioxidant and inflammatory responses in elite female players.
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| 9. |
- Folkesson, Mattias, 1972-
(författare)
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Heat shock proteins in exercised human skeletal muscle
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Exercise is considered as an important stressor accompanied by concerted molecular and cellular changes leading to adaptations at the level of skeletal muscle size and function. An important protein family produced by cells in response to stressful conditions is the heat shock proteins (HSPs). It is suggested that the different HSPs play specific roles in acute and longterm responses to exercise-induced stress. The overall aim of this thesis was to explore the expression of four different HSPs (αB-crystallin, HSP27, HSP60 and HSP70) in human skeletal muscle exposed to exercise, with a special emphasis on the role played by HSP27 in the hypertrophy of human skeletal muscle.One of the major findings was the fibre type-specific expression of HSPs in resting human skeletal muscle, including the preferential expression of HSP27 in fast type II muscle fibres. Another finding was the occurrence of training background-related differences in the expression of HSPs. Also, a cytoplasmic relocation of HSP27, occurring specifically in type II muscle fibres, was shown in response to a single bout of resistance exercise. Interestingly, there were no corresponding changes in response to an endurance exercise bout, suggesting that HSP27 may be specifically involved in the adaptations to resistance exercise. In order to test this hypothesis, an in-vitro exercise model based on the electrical pulse stimulation (EPS) of muscle cells was developed. The EPS protocol, including an 8 h restitution period, induced a significant hypertrophy of muscle cells together with molecular changes similar to those previously described in response to exercise in humans. The role of HSP27 in the hypertrophy of human muscle cells was examined through the downregulation of HSP27. Based on data from morphological and microarray analyses, findings indicate that HSP27 is not mandatory for the hypertrophy of human muscle cells. Overall, the present thesis clarified the expression of different HSPs in human skeletal muscle and provided an in-vitro-based approach for the elucidation of the exact role played by HSPs in the adaptations of human skeletal muscle to exercise.
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| 10. |
- Papaioannou, Konstantinos-Georgios, 1983-
(författare)
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Diet and physical activity behaviors for healthy aging
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The process of aging is characterized by physiological changes in various body systems and biological functions, that affect health and functional capacity. Adopting healthy lifestyle behaviors could be an effective, accessible, and lowcost strategy to delay age-related functional changes. Dietary habits, including both patterns and amounts of specific food items, and physical activity (PA)are two lifestyle factors that may have an impact on several age-related health aspects. The overall aim of this thesis was to determine the links between diet, physical activity behaviors, and biological markers of healthy aging, including muscle health, metabolic health, and systemic inflammation in older adults.The findings of the present work collectively highlight the role of diet and physical activity behaviors on biological markers of healthy aging in older adults. Daily amounts of sedentary time were detrimentally associated with the systemic inflammatory environment, with sex-specific alterations in proand anti-inflammatory biomarkers. In term of dietary habits, higher intakes of vegetables were associated with lower levels of the pro-inflammatory biomarker IL-6 in older adults, regardless of intakes of other health-related food groups, physical activity behaviors, and adiposity level. Moreover, lower intakes of fruit and vegetables (FV) in general, and of vegetables in particular, increased the likelihood of having metabolic syndrome (MetS) in older adults, which was evident even after considering time spent in sedentary behavior and adherence to the moderate-to-vigorous physical activity (MVPA) guideline. Finally, healthy eating was beneficially associated with lower sarcopenia risk in physically active older men and women, even when engagement in musclestrengthening activities and adherence to guidelines for protein intake were considered. Overall, the present thesis demonstrates the detrimental impact of excessive amounts of sedentary time on markers of systemic inflammation and highlights the beneficial effects of healthy eating on biological determinants of healthy aging regardless of the potential confounding effects of physical activity behaviors.
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