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==Publications==

{{medline-entry
|title=Aging reduces the maximal level of peripheral fatigue tolerable and impairs exercise capacity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32966120
|abstract=The aim of the present study was to determine the magnitude of the maximal level of peripheral fatigue attainable (fatigue threshold) during an all-out intermittent isometric knee-extensor protocol in both younger (24 ± 1 yr, [i]n[/i] = 12) and older (60 ± 2 yr, [i]n[/i] = 12) participants to provide new insights into the effects of aging on neuromuscular function. Participants performed two experimental sessions, in which they performed 60 maximal voluntary contractions (MVCs; 3 s of contraction, 2 s of relaxation). One trial was performed in the unfatigued state ([[CTRL]]) and one other following fatiguing neuromuscular electrical stimulation of the quadriceps (F ). Peripheral fatigue was quantified via pre/postexercise decrease in quadriceps twitch force (∆P ). Critical force (CF) was determined as the mean force output of the last 12 contractions, whereas [i]W[/i]' was calculated as the area above CF. Although F  led to a significant decrease in P  before performing the 60-MVCs protocol ([i]P[/i] = 0.024), ∆P  was not different between [[CTRL]] and F  for both the young group ([i]P[/i] = 0.491) and the old group ([i]P[/i] = 0.523). However, this peripheral fatigue threshold was significantly greater in young versus old participants (∆P  = -48 ± 10% vs. -29 ± 13%, respectively, [i]P[/i] = 0.028). In [[CTRL]], [i]W'[/i] was 55 ± 13% lower in the old group than in the young group ([i]P[/i] < 0.001), but CF was similar (326 ± 10 N vs. 322 ± 12 N, respectively, [i]P[/i] = 0.941). ∆P  was correlated with [i]W'[/i], independently of age ([i]r[/i]  = 0.84, [i]P[/i] < 0.001). Exercise performance decreases with aging consequent to a lower tolerance to peripheral fatigue. However, the peripheral fatigue threshold mechanism persists with healthy aging and continues to play a protective role in preserving locomotor muscle function during exercise.

|keywords=* aging
* critical torque
* exercise performance
* group III/IV muscle afferents
* neuromuscular fatigue
|full-text-url=https://sci-hub.do/10.1152/ajpregu.00151.2020
}}
{{medline-entry
|title=miR-146a Plasma Levels Are Not Altered in Alzheimer's Disease but Correlate With Age and Illness Severity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32009940
|abstract=miR-146a is a microRNA (miRNA) involved in neuroinflammation and aging; alterations in its expression were described in Alzheimer's disease (AD). However, most of the studies conducted so far on this miRNA included a limited number of participants and produced contradictory results. We compared miR-146a levels in plasma from 33 AD patients vs. 28 age-matched non-affected controls ([[CTRL]]) through quantitative real-time polymerase chain reaction (qRT-PCR). No difference between the case and the control group was evidenced, but a correlation was detected between miR-146a levels and subjects' age ([i]p[/i] < 0.001) as well as between miR-146a levels and patients' Mini-Mental State Examination (MMSE) scores ([i]p[/i] = 0.011), in an enlarged group of 51 AD patients and 45 [[CTRL]] supporting a role for this miRNA in aging processes and disease progression.

|keywords=* Alzheimer’s disease
* aging
* blood
* miR-146a
* microRNA
* plasma
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978630
}}
{{medline-entry
|title=Centrally-mediated regulation of peripheral fatigue during knee extensor exercise and consequences on the force-duration relationship in older men.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31397211
|abstract=The aim of the present study was to investigate the existence of a critical threshold beyond which peripheral fatigue would not further decrease during knee extensor (KE) exercise in older men, and the consequences of this mechanism on the force-duration relationship. Twelve old men (59 ± 2 years) randomly performed two different sessions, in which they performed 60 maximum voluntary contractions (MVC; 3s contraction, 2s relaxation). One trial was performed in the unfatigued state ([[CTRL]]) and one other following fatiguing neuromuscular electrical stimulation of the KE (F ). Peripheral and central fatigue were quantified via pre/post-exercise decreases in quadriceps twitch-force (Δ P ) and voluntary activation (ΔVA). Critical torque (CT) was determined as the mean force of the last 12 contractions while W' was calculated as the area above CT. Compared with [[CTRL]], pre-fatigue (Δ P = -10.3 ± 6.2%) resulted in a significant ([i]p[/i] < 0.05) reduction in W' (-18.2 ± 1.6%) in F . However, CT (∼964 N), ΔVA (∼15%) and Δ P  (∼25%) post-MVCs were similar between both conditions. In [[CTRL]], W' was correlated with Δ P  ([i]r[/i]   = 0.78). Moreover, the difference in W' between [[CTRL]] and F  was correlated with the level of pre-fatigue induced in F  ([i]r[/i]   = 0.76). These findings document that peripheral fatigue is confined to an individual threshold during KE exercise in older men. Furthermore, correlative results suggest that mechanisms regulating peripheral fatigue to a critical threshold also restrict W', and therefore play a role in exercise capacity in older men.

|keywords=* Aging
* critical torque
* group III/IV muscle afferents
|full-text-url=https://sci-hub.do/10.1080/17461391.2019.1655099
}}
{{medline-entry
|title=Non-linear registration improves statistical power to detect hippocampal atrophy in aging and dementia.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/31233953
|abstract=To compare the performance of different methods for determining hippocampal atrophy rates using longitudinal MRI scans in aging and Alzheimer's disease (AD). Quantifying hippocampal atrophy caused by neurodegenerative diseases is important to follow the course of the disease. In dementia, the efficacy of new therapies can be partially assessed by measuring their effect on hippocampal atrophy. In radiotherapy, the quantification of radiation-induced hippocampal volume loss is of interest to quantify radiation damage. We evaluated plausibility, reproducibility and sensitivity of eight commonly used methods to determine hippocampal atrophy rates using test-retest scans. Manual, FSL-FIRST, FreeSurfer, multi-atlas segmentation (MALF) and non-linear registration methods (Elastix, NiftyReg, ANTs and MIRTK) were used to determine hippocampal atrophy rates on longitudinal T1-weighted MRI from the ADNI database. Appropriate parameters for the non-linear registration methods were determined using a small training dataset (N = 16) in which two-year hippocampal atrophy was measured using test-retest scans of 8 subjects with low and 8 subjects with high atrophy rates. On a larger dataset of 20 controls, 40 mild cognitive impairment (MCI) and 20  AD patients, one-year hippocampal atrophy rates were measured. A repeated measures ANOVA analysis was performed to determine differences between controls, MCI and AD patients. For each method we calculated effect sizes and the required sample sizes to detect one-year volume change between controls and MCI (N ) and between controls and AD (N ). Finally, reproducibility of hippocampal atrophy rates was assessed using within-session rescans and expressed as an average distance measure D , which expresses the difference in atrophy rate, averaged over all subjects. The same D  was used to determine the agreement between different methods. Except for MALF, all methods detected a significant group difference between [[CTRL]] and AD, but none could find a significant difference between the [[CTRL]] and MCI. FreeSurfer and MIRTK required the lowest sample sizes (FreeSurfer: N  = 115, N  = 17 with D  = 3.26%; MIRTK: N  = 97, N  = 11 with D  = 3.76%), while ANTs was most reproducible (N  = 162, N  = 37 with D  = 1.06%), followed by Elastix (N  = 226, N  = 15 with D  = 1.78%) and NiftyReg (N  = 193, N  = 14 with D  = 2.11%). Manually measured hippocampal atrophy rates required largest sample sizes to detect volume change and were poorly reproduced (N  = 452, N  = 87 with D  = 12.39%). Atrophy rates of non-linear registration methods also agreed best with each other. Non-linear registration methods were most consistent in determining hippocampal atrophy and because of their better reproducibility, methods, such as ANTs, Elastix and NiftyReg, are preferred for determining hippocampal atrophy rates on longitudinal MRI. Since performances of non-linear registration methods are well comparable, the preferred method would mostly depend on computational efficiency.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Alzheimer Disease
* Atrophy
* Cognitive Dysfunction
* Databases, Factual
* Female
* Hippocampus
* Humans
* Image Processing, Computer-Assisted
* Magnetic Resonance Imaging
* Male
* Neuroimaging
|keywords=* AD
* Automatic segmentation
* Hippocampal atrophy
* Longitudinal MRI
* MCI
* Non-linear registration
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595082
}}
{{medline-entry
|title=Plyometric exercise improves jumping performance and skeletal muscle contractile properties in seniors.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30839302
|abstract=This study investigated the effects of an 8-week plyometric training (PT) session on countermovement jump (CMJ) height, take-off velocity, and Tensiomyography (TMG) derived contractile parameters in seniors. Twenty-three senior adults (age 66.7±5.2 years) were randomly divided into two groups: PLYO (n=11) and [[CTRL]] (n=12). Tensiomyography was measured in vastus lateralis (VL), biceps femoris (BF), tibialis anterior (TA), gastrocnemius medialis (GM), and lateralis (GL). Additionally, the electromechanical efficiency (EME) index was calculated in GM as a ratio between amplitudes of peak-to-peak M-wave and TMG (Dm) responses. Biochemical markers of muscle damage and inflammation were evaluated to provide indirect indices of exercise protocol safety. The main effect of time (for take-off velocity p=.023; ɳ = .236) and group x time interactions (for CMJ, Tc (BF, GM), Dm (BF) and EME p<.05; ɳ = .136 - .236) were observed. Post hoc analysis showed a significant increase in CMJ height and take-off velocity, namely by 14.2% (p=.001) and 8.2% (p=.01) in PLYO, respectively. Contraction time (Tc) decreased in BF -5.7% (p=.001) and GM -9.6% (p=.001). Dm decreased only in BF -20.8% (p=.001), while the EME index of the GM improved by 22.9% (p=.002). There were no differences between groups or assessment time points for C-reactive protein (p=.122). The present study clearly supports the application of supervised PT exercise in seniors, since explosive power, muscle contractility, and EME of the lower limbs were markedly improved after training.
|mesh-terms=* Aged
* Aging
* Female
* Humans
* Male
* Muscle Contraction
* Muscle Strength
* Muscle, Skeletal
* Plyometric Exercise

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454255
}}
{{medline-entry
|title=Soy isoflavones protect against oxidative stress and diminish apoptosis in ovary of middle-aged female rats.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30784335
|abstract=Ovarian aging is characterized by declines in follicular reserve and oocyte quality due, in part, to increased oxidative stress and apoptosis. Soy isoflavones (ISOs) have been shown to improve ovarian lifespan by acting as antioxidant and antiapoptotic agents. We aimed at evaluating whether ISOs could modulate oxidative stress and reduce apoptosis and improve ovarian follicle survival in middle-aged female rats. Twelve ovary-intact female Wistar rats (12-month-old) were divided into groups: control ([[CTRL]]) and ISO, daily treated by gavage with vehicle or soy-ISO extract (150 mg/kg b.w), respectively. After 8 weeks, rats were euthanized and their ovaries removed for histomorphometric (% follicles) and apoptosis (cleaved-caspase-3/[[BCL2]] immunostaining) evaluations, or subjected to biochemical assays to survey reactive oxygen species (ROS) and lipid peroxidation levels and total antioxidant capacity (TAC). The frequency of atretic follicles and number of cleaved-caspase-3-positive cells, as well as the ROS and lipid peroxidation levels, were significantly lower in ISO group compared to [[CTRL]]. A significantly higher number of [[BCL2]]-positive cells and TAC levels were also observed in ISO group. In conclusion, soy ISOs could decrease follicular atresia, apoptosis and oxidative stress, as well as increase the TAC in ovaries of female rats.
|mesh-terms=* Animals
* Apoptosis
* Caspase 3
* Female
* Isoflavones
* Ovary
* Oxidative Stress
* Protective Agents
* Rats
* Rats, Wistar
* Reactive Oxygen Species
|keywords=* apoptosis
* ovarian aging
* oxidative stress
* rats
* soy isoflavones
|full-text-url=https://sci-hub.do/10.1080/09513590.2018.1559287
}}
{{medline-entry
|title=Heterogeneity of Thyroid Function and Impact of Peripheral Thyroxine Deiodination in Centenarians and Semi-Supercentenarians: Association With Functional Status and Mortality.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30165411
|abstract=Thyroid hormones (FT3, FT4) and thyroid-stimulating hormone (TSH) were evaluated in a population of 672 well-characterized Italian subjects (age range: 52-113 years), including an unprecedented number of centenarians, semi-supercentenarians, as well as centenarian's offspring and age-matched elderly (CENT, 105 , CENTOFF, and [[CTRL]], respectively). The results show that FT3 level and FT3/FT4 ratio decrease while FT4 and TSH increase in an age-dependent manner. In CENT/105 , higher FT4 level, and lower FT3/FT4 ratio are associated with an impaired functional status and an increased mortality. A cluster analysis identified three clusters of CENT/105  based on their FT3, FT4, and TSH levels. Cluster 3, characterized by lower FT3 and TSH and higher FT4, shows the worst health status and the shortest survival. Thus, the age-related changes of thyroid hormones extend to the most advanced age, and CENT/105  are highly heterogeneous regarding thyroid function. This heterogeneity is related to different health, functional and cognitive status, as well as with survival/mortality in CENT/105 . Finally, we investigated a remarkable number of CENT/105  showing a thyroid profile suggestive of non-thyroidal illness syndrome (NTIS) (excluded from the previous analysis). NTIS CENT/105  are characterized by a worse functional and cognitive status and an increased mortality with respect to CENT/105  without NTIS.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Blood Proteins
* Cholesterol, HDL
* Cognition
* Depression
* Disability Evaluation
* Female
* Hand Strength
* Health Status
* Humans
* Insulin
* Insulin Resistance
* Longevity
* Male
* Middle Aged
* Mortality
* Thyrotropin
* Thyroxine
* Triiodothyronine
|keywords=* Health
* Human aging
* Longevity
* Mortality
* Thyroid hormones
|full-text-url=https://sci-hub.do/10.1093/gerona/gly194
}}
{{medline-entry
|title=Evaluation of Lymphocyte Response to the Induced Oxidative Stress in a Cohort of Ageing Subjects, including Semisupercentenarians and Their Offspring.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/29681767
|abstract=The production of reactive oxygen species (ROS) may promote immunosenescence if not counterbalanced by the antioxidant systems. Cell membranes, proteins, and nucleic acids become the target of ROS and progressively lose their structure and functions. This process could lead to an impairment of the immune response. However, little is known about the capability of the immune cells of elderly individuals to dynamically counteract the oxidative stress. Here, the response of the main lymphocyte subsets to the induced oxidative stress in semisupercentenarians (CENT), their offspring (OFF), elderly controls ([[CTRL]]), and young individuals (YO) was analyzed using flow cytometry. The results showed that the ratio of the ROS levels between the induced and noninduced (I/NI) oxidative stress conditions was higher in [[CTRL]] and OFF than in CENT and YO, in almost all T, B, and NK subsets. Moreover, the ratio of reduced glutathione levels between I/NI conditions was higher in OFF and CENT compared to the other groups in almost all the subsets. Finally, we observed significant correlations between the response to the induced oxidative stress and the degree of methylation in specific genes on the oxidative stress pathway. Globally, these data suggest that the capability to buffer dynamic changes in the oxidative environment could be a hallmark of longevity in humans.
|mesh-terms=* Age Factors
* Aged
* Aged, 80 and over
* Aging
* Antioxidants
* Cells, Cultured
* Female
* Flow Cytometry
* Glutathione
* Humans
* Lymphocytes
* Male
* Middle Aged
* Oxidation-Reduction
* Oxidative Stress
* Reactive Oxygen Species

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842690
}}
{{medline-entry
|title=Effects of a 20-week high-intensity strength and sprint training program on tibial bone structure and strength in middle-aged and older male sprint athletes: a randomized controlled trial.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28623425
|abstract=This randomized, controlled, high-intensity strength and sprint training trial in middle-aged and older male sprint athletes showed significant improvements in mid-tibial structure and strength. The study reveals the adaptability of aging bone, suggesting that through a novel, intensive training stimulus it is possible to strengthen bones during aging. High-load, high-speed and impact-type exercise may be an efficient way of improving bone strength even in old age. We evaluated the effects of combined strength and sprint training on indices of bone health in competitive masters athletes, who serve as a group of older people who are likely to be able to participate in vigorous exercise of this kind. Seventy-two men (age 40-85) were randomized into an experimental (EX, n = 40) and a control ([[CTRL]], n = 32) group. EX participated in a 20-week program combining heavy and explosive strength exercises with sprint training. [[CTRL]] maintained their usual, run-based sprint training schedules. Bone structural, strength and densitometric parameters were assessed by peripheral QCT at the distal tibia and tibial midshaft. The intervention had no effects on distal tibia bone traits. At the mid-tibia, the mean difference in the change in cortical thickness (Th ) in EX compared to [[CTRL]] was 2.0% (p = 0.007). The changes in structure and strength were more pronounced in the most compliant athletes (training adherence >75%). Compared to [[CTRL]], total and cortical cross-sectional area, Th , and the area and density-weighted moments of inertia for the direction of the smallest flexural rigidity (I   , I   ) increased in EX by 1.6-3.2% (p = 0.023-0.006). Polar mass distribution analysis revealed increased BMC at the anteromedial site, whereas vBMD decreased (p = 0.035-0.043). Intensive strength and sprint training improves mid-tibia structure and strength in middle-aged and older male sprint athletes, suggesting that in the presence of high-intensity loading exercise, the adaptability of the bone structure is maintained during aging.
|mesh-terms=* Adult
* Aged
* Aged, 80 and over
* Aging
* Anthropometry
* Athletes
* Athletic Performance
* Bone Density
* Humans
* Male
* Middle Aged
* Patient Compliance
* Physical Conditioning, Human
* Running
* Tibia
* Tomography, X-Ray Computed
|keywords=* Aging
* BMD
* Bone pQCT
* Exercise
* High-impact training
* Masters athlete
* Strength training
|full-text-url=https://sci-hub.do/10.1007/s00198-017-4107-z
}}
{{medline-entry
|title=Effect of concurrent resistance and sprint training on body composition and cardiometabolic health indicators in masters cyclists.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27807523
|abstract=In older previously sedentary individuals endurance training imposes a more effective stimulus to enhance cardiometabolic health compared with resistance or sprint training. We examined the effect of replacing a portion of endurance training with combined resistance and/or sprint training and how this influences cardiometabolic health indicators in masters endurance cyclists. Twenty-seven well-trained male road cyclists (53.7±8.2 years) were allocated to a resistance and track sprint-cycling training group (RTC, n=10), an endurance and track sprint-cycling group (ETC, n=7) or a control endurance group ([[CTRL]], n=10). Both the RTC and ETC groups completed a 12-week intervention of specific training while the [[CTRL]] group maintained their endurance training load. Lower limb lean mass (LLM), trunk fat mass (TFM), fasting blood glucose (FBG), total cholesterol (TC), triglycerides ([[TG]]), systolic blood pressure (SBP), and diastolic blood pressure ([[DBP]]) were measured before and after the intervention period. TFM decreased for all groups ([i]P[/i]<0.05) while LLM significantly increased for RTC and ETC groups ([i]P[/i]<0.05). No significant between group or time effects were observed for FBG, TC, [[TG]], SBP, or [[DBP]]. The results suggest that replacing a portion of endurance training with 12 weeks of ETC or RTC training favourably affects body composition by lowering TFM and increasing LLM without negatively affecting cardiometabolic health indicators in well-trained masters endurance cyclists.

|keywords=* Aging
* Blood lipids
* Blood pressure
* Cycling
* Resistance training
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5091060
}}
{{medline-entry
|title=Motor effort training with low exercise intensity improves muscle strength and descending command in aging.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/27310942
|abstract=This study explored the effect of high mental effort training ([[MET]]) and conventional strength training (CST) on increasing voluntary muscle strength and brain signal associated with producing maximal muscle force in healthy aging. Twenty-seven older adults (age: 75 ± 7.9 yr, 8 women) were assigned into 1 of 3 groups: [[MET]] group-trained with low-intensity (30% maximal voluntary contraction [MVC]) physical exercise combined with [[MET]], CST group-trained with high-intensity muscle contractions, or control ([[CTRL]]) group-no training of any kind. [[MET]] and CST lasted for 12 weeks (5 sessions/week). The participants' elbow flexion strength of the right arm, electromyography (EMG), and motor activity-related cortical potential (MRCP) directly related to the strength production were measured before and after training. The CST group had the highest strength gain (17.6%, P <0.001), the [[MET]] group also had significant strength gain (13.8%, P <0.001), which was not statistically different from that of the CST group even though the exercise intensity for the [[MET]] group was only at 30% MVC level. The [[CTRL]] group did not have significant strength changes. Surprisingly, only the [[MET]] group demonstrated a significant augmentation in the MRCP (29.3%, P <0.001); the MRCP increase in CST group was at boarder-line significance level (12.11%, P = 0.061) and that for [[CTRL]] group was only 4.9% (P = 0.539). These results suggest that high mental effort training combined with low-intensity physical exercise is an effective method for voluntary muscle strengthening and this approach is especially beneficial for those who are physically weak and have difficulty undergoing conventional strength training. 
|mesh-terms=* Aged
* Aging
* Electromyography
* Exercise
* Female
* Humans
* Motor Skills
* Muscle Contraction
* Muscle Strength
* Resistance Training

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998428
}}
{{medline-entry
|title=Gastrocnemius medialis muscle architecture and physiological cross sectional area in adult males with Duchenne muscular dystrophy.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26032207
|abstract=To describe muscle size and architecture of the gastrocnemius medialis (GM) muscle in eleven adult males with Duchenne Muscular Dystrophy ([[DMD]], age 24.5±5.4 years), and a control group of eleven males without [[DMD]] ([[CTRL]], age 22.1±0.9 years). GM anatomical cross sectional area (ACSA), volume (VOL), physiological cross sectional area (PCSA), fascicle length (Lf) and pennation angle (θ) were assessed using B-Mode Ultrasonography. GM ACSA was measured at 25, 50 and 75% of muscle length (Lm), from which VOL was calculated. At 50% of Lm, sagittal plane images were analysed to determine GM Lf and θ. GM PCSA was calculated as: VOL/Lf. The ratio of Lf and Lm was also calculated. GM ACSA at 50% Lm, VOL and PCSA were smaller in [[DMD]] males compared to [[CTRL]] males by 36, 47 and 43%, respectively (P<0.01). There were no differences in Lf and θ. GM Lm was 29% shorter in [[DMD]] compared to [[CTRL]]. Lf/Lm was 29% longer in [[DMD]] (P<0.01). Unlike previous data in children with [[DMD]], our results show significant atrophy in adult males with [[DMD]], and no change in Lf or θ. The shorter Lm may have implications for joint flexibility.
|mesh-terms=* Adult
* Aging
* Anatomy, Cross-Sectional
* Body Height
* Body Weight
* Humans
* Male
* Muscle, Skeletal
* Muscular Dystrophy, Duchenne
* Ultrasonography
* Young Adult

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133718
}}
{{medline-entry
|title=Deranged myofilament phosphorylation and function in experimental heart failure with preserved ejection fraction.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/23213108
|abstract=Heart failure (HF) with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality. Key alterations in HFpEF include increased left ventricular (LV) stiffness and abnormal relaxation. We hypothesized that myofilament protein phosphorylation and function are deranged in experimental HFpEF vs. normal myocardium. Such alterations may involve the giant elastic protein titin, which contributes decisively to LV stiffness. LV tissue samples were procured from normal dogs ([[CTRL]]) and old dogs with hypertension-induced LV hypertrophy and diastolic dysfunction (OHT/HFpEF). We quantified the expression and phosphorylation of myofilament proteins, including all-titin and site-specific titin phosphorylation, and assessed the expression/activity of major protein kinases (PKs) and phosphatases (PPs), myofilament calcium sensitivity (pCa(50)), and passive tension (F(passive)) of isolated permeabilized cardiomyocytes. In OHT vs. [[CTRL]] hearts, protein kinase-G (PKG) activity was decreased, whereas PKCα activity and PP1/PP2a expression were increased. Cardiac MyBPC, TnT, TnI and MLC2 were less phosphorylated and pCa(50) was increased in OHT vs. [[CTRL]]. The titin N2BA (compliant) to N2B (stiff) isoform-expression ratio was lowered in OHT. Hypophosphorylation in OHT was detected for all-titin and at serines S4010/S4099 within titin-N2Bus, whereas S11878 within proline, glutamate, valine, and lysine (PEVK)-titin was hyperphosphorylated. Cardiomyocyte F(passive) was elevated in OHT, but could be normalized by PKG or PKA, but not PKCα, treatment. This patient-mimicking HFpEF model is characterized by titin stiffening through altered isoform composition and phosphorylation, both contributing to increased LV stiffness. Hypophosphorylation of myofilament proteins and increased calcium sensitivity suggest that functional impairment at the sarcomere level may be an early event in HFpEF.
|mesh-terms=* Aging
* Animals
* Calcium
* Cardiac Myosins
* Cells, Cultured
* Connectin
* Cyclic AMP-Dependent Protein Kinases
* Cyclic GMP-Dependent Protein Kinases
* Disease Models, Animal
* Dogs
* Heart Failure
* Heart Ventricles
* Muscle Proteins
* Myocytes, Cardiac
* Myofibrils
* Myosin Light Chains
* Phosphorylation
* Protein Kinases
* Stroke Volume

|full-text-url=https://sci-hub.do/10.1093/cvr/cvs353
}}
{{medline-entry
|title=Skeletal muscle remodeling in response to alpine skiing training in older individuals.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/21679320
|abstract=This study investigated whether regular alpine skiing could reverse sarcopenia and muscle weakness in older individuals. Twenty-two older men and women (67 ± 2 years) underwent 12 weeks of recreational skiing, two to three times a week, each session lasting ∼ 3.5 h. An age-matched, inactive group (n=20, 67 ± 4 years) served as a control ([[CTRL]]). Before and after the training period, knee extensors muscle thickness (T(m) ), pennation angle (θ) and fascicle length (L(f) ) of the vastus lateralis muscle were measured by ultrasound. Maximum isokinetic knee extensor torque (MIT) at an angular velocity of 60°/s was measured by dynamometry. After the training, T(m) increased by 7.1% (P<0.001), L(f) by 5.4% (P<0.02) and θ by 3.4% (P<0.05). The increase in T(m) was matched by a significant gain in MIT (13.3%, P<0.001). No significant changes, except for a decrease in θ (2.1%, P<0.02), were found in the [[CTRL]] group. The gain in T(m) in the training group correlated significantly with an increase in the focal adhesion kinase content, pointing to a primary role of this mechano-sensitive protein in sarcomere remodeling with muscle hypertrophy. Overall, the results show that alpine skiing is an effective intervention for combating sarcopenia and weakness in old age.
|mesh-terms=* Adaptation, Physiological
* Age Factors
* Aged
* Aging
* Analysis of Variance
* Female
* Humans
* Male
* Muscle Contraction
* Muscle Strength Dynamometer
* Muscle Weakness
* Muscle, Skeletal
* Sarcopenia
* Skiing
* Statistics as Topic
* Torque
* Weight-Bearing

|full-text-url=https://sci-hub.do/10.1111/j.1600-0838.2011.01338.x
}}
{{medline-entry
|title=Parafoveal letter recognition at reduced contrast in normal aging and in patients with risk factors for AMD.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/18751995
|abstract=Patients with early age-related maculopathy (ARM) do not necessarily show obvious morphological signs or functional impairment. Many have good visual acuity, yet complain of decreased visual performance. The aim of this study was to investigate the aging effects on performance of parafoveal letter recognition at reduced contrast, and defects caused by early ARM and normal fellow eyes of patients with unilateral age-related macular degeneration (nfAMD). Testing of the central visual field (8 degrees radius) was performed by the Macular Mapping Test (MMT) using recognition of letters in 40 parafoveal target locations at four contrast levels (5, 10, 25 and 100%). Effects of aging were investigated in 64 healthy subjects aged 23 to 76 years ([[CTRL]]). In addition, 39 eyes (minimum visual acuity of 0.63;20/30) from 39 patients with either no visible signs of ARM, while the fellow eye had advanced age-related macular degeneration (nfAMD; n = 12), or early signs of ARM (eARM; n = 27) were examined. Performance was expressed summarily as a "field score" (FS). Performance in the MMT begins to decline linearly with age in normal subjects from the age of 50 and 54 years on, at 5% and 10% contrast respectively. The differentiation between patients and [[CTRL]]s was enhanced if FS at 5% was analyzed along with FS at 10% contrast. In 8/12 patients from group nfAMD and in 18/27 from group eARM, the FS was statistically significantly lower than in the [[CTRL]] group in at least one of the lower contrast levels. Using parafoveal test locations, a recognition task and diminished contrast increases the chance of early detection of functional defects due to eARM or nfAMD and can differentiate them from those due to aging alone.
|mesh-terms=* Adult
* Age Distribution
* Aged
* Aging
* Contrast Sensitivity
* Early Diagnosis
* Fovea Centralis
* Humans
* Macular Degeneration
* Mass Screening
* Middle Aged
* Models, Biological
* Prognosis
* Reproducibility of Results
* Risk Factors
* Sensitivity and Specificity
* Vision Tests
* Visual Acuity
* Visual Fields
* Young Adult

|full-text-url=https://sci-hub.do/10.1007/s00417-008-0919-z
}}
{{medline-entry
|title=Aerobic exercise overcomes the age-related insulin resistance of muscle protein metabolism by improving endothelial function and Akt/mammalian target of rapamycin signaling.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17351147
|abstract=Muscle protein metabolism is resistant to insulin's anabolic effect in healthy older subjects. This is associated with reduced insulin vasodilation. We hypothesized that aerobic exercise restores muscle protein anabolism in response to insulin by improving vasodilation in older subjects. We measured blood flow, endothelin-1, Akt/mammalian target of rapamycin (mTOR) signaling, and muscle protein kinetics in response to physiological local hyperinsulinemia in two groups of older subjects following a bout of aerobic exercise (EX group: aged 70  /- 2 years; 45-min treadmill walk, 70% heart rate max) or rest ([[CTRL]] group: aged 68  /- 1 years). Baseline endothelin-1 was lower and blood flow tended to be higher in the EX group, but protein kinetics was not different between groups. Insulin decreased endothelin-1 (P < 0.05) in both groups, but endothelin-1 remained higher in the [[CTRL]] group (P < 0.05) and blood flow increased only in the EX group (EX group: 3.8  /- 0.7 to 5.3  /- 0.8; [[CTRL]] group: 2.5  /- 0.2 to 2.6  /- 0.2 ml x min(-1) x 100 ml leg(-1)). Insulin improved Akt phosphorylation in the EX group and increased mTOR/S6 kinase 1 phosphorylation and muscle protein synthesis (EX group: 49  /- 11 to 89  /- 23; [[CTRL]] group: 58  /- 8 to 57  /- 12 nmol x min(-1) x 100 ml leg(-1)) in the EX group only (P < 0.05). Because breakdown did not change, net muscle protein balance became positive only in the EX group (P < 0.05). In conclusion, a bout of aerobic exercise restores the anabolic response of muscle proteins to insulin by improving endothelial function and Akt/mTOR signaling in older subjects.
|mesh-terms=* Aerobiosis
* Aged
* Aging
* Blood Flow Velocity
* Body Mass Index
* Endothelium, Vascular
* Female
* Humans
* Insulin Resistance
* Kinetics
* Male
* Muscle Proteins
* Protein Kinases
* Proto-Oncogene Proteins c-akt
* Reference Values
* Signal Transduction
* TOR Serine-Threonine Kinases

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2740742
}}
{{medline-entry
|title=Deterioration of contractile properties of muscle fibres in elderly subjects is modulated by the level of physical activity.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17273882
|abstract=The impact of ageing on force and velocity of human skeletal muscle fibres has been extensively studied. As discrepancies have been reported, it is still unclear whether or not a deterioration of the capacity of muscle fibres to develop force and shortening is involved in determining weakness and decrease in shortening velocity of skeletal muscle of elderly people. We compared myosin heavy chain (MHC) isoform distribution of vastus lateralis muscle, and specific force (Po/CSA) and maximum shortening velocity (Vo) of skeletal muscle fibres among one population of young controls ([[CTRL]]) and three populations of elderly (EL) subjects with very variable levels of physical activity: sedentary (EL-SED, n = 3); controls (EL-[[CTRL]], n = 4); endurance trained (EL-END, n = 3). Muscle phenotype was progressively faster in the order EL-END --> [[CTRL]] --> EL-[[CTRL]] --> EL-SED. Po/CSA and Vo also varied among the different populations of elderly subjects generally showing a decreasing deterioration with increasing activity levels. The results suggest that discrepancies observed so far in age-induced deterioration of contractile properties of muscle fibres could depend on the different activity levels of the populations of elderly subjects enrolled in the studies.
|mesh-terms=* Adult
* Aged
* Aging
* Exercise
* Humans
* Muscle Contraction
* Muscle Fibers, Skeletal
* Muscle Strength
* Myosin Heavy Chains
* Protein Isoforms
* Quadriceps Muscle

|full-text-url=https://sci-hub.do/10.1007/s00421-007-0402-2
}}
{{medline-entry
|title=Gastrocnemius specific force is increased in elderly males following a 12-month physical training programme.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16858613
|abstract=The aim of the present investigation was to determine whether muscle force per physiological cross sectional area (PCSA) of the lateral gastrocnemius (GL) of elderly males increased following a 12-month physical training programme. Eleven elderly males were assigned to a 12-month training programme (TRN mean age 72.7  /- 3.3 years, mean  /- SD) and eight elderly males were allocated to a control group ([[CTRL]], 73.9  /- 4.0 years) who maintained their habitual physical activity levels. In vivo measurements of muscle architecture, muscle volume (VOL), achilles tendon moment arm length and plantarflexor torque were used to estimate GL PCSA (VOL/fascicle length) and specific force (GL fascicle force/GL PCSA). Maximal GL fascicle force was calculated accounting for agonist muscle activation and antagonist co-activation. Following training GL fascicle force increased by 31% (P < 0.01), which was not entirely accounted for by a 17% increase in PCSA (from 27.2  /- 5.9 to 31.8  /- 6.2 cm(2), P < 0.05). Specific force increased significantly from 8.9  /- 1.9 to 11.2  /- 3.0 N cm(-2) (P < 0.05). Pennation angle, but not fascicle length, increased by 12% with training (P < 0.05). The [[CTRL]] group showed no change in muscle size, strength or architecture over the 12-month period. In conclusion, with the level of agonist and antagonist muscle activity accounted for a 12-month strength training programme resulted in an increase in both PCSA and specific force in elderly males.
|mesh-terms=* Achilles Tendon
* Adaptation, Physiological
* Aged
* Aging
* Double-Blind Method
* Humans
* Isometric Contraction
* Male
* Muscle Contraction
* Muscle Strength
* Muscle, Skeletal
* Physical Education and Training
* Physical Fitness
* Torque

|full-text-url=https://sci-hub.do/10.1007/s00421-006-0246-1
}}
{{medline-entry
|title=Muscle strength, volume and activation following 12-month resistance training in 70-year-old males.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16003538
|abstract=In elderly males muscle plantar flexor maximal voluntary contraction (MVC) torque normalised to muscle volume (MVC/VOL) is reduced compared to young males as a result of incomplete muscle activation in the elderly. The aim of the present study was to determine the influence of a 12-month resistance training programme on muscle volume, strength, MVC/VOL, agonist activation and antagonist coactivation of the plantarfexors in elderly males. Thirteen elderly males aged 70 years and over (range 70-82 years), completed a 12-month whole body resistance-training programme (TRN), training three times a week. Another eight males (range 18-30 years), who maintained their habitual physical activity for the same 12-month period as the TRN group acted as controls ([[CTRL]]). Isometric plantarflexor maximal voluntary contraction (MVC) torque increased in the TRN group by 20% (P < 0.01), from 113.1  /- 22.0 Nm to 141.5  /- 19.2 Nm. Triceps surae volume (TS VOL) assessed using MRI, increased by 12%, from 796.3  /- 78.9 cm(3) to 916.8  /- 144.4 cm(3) . PF activation, measured using supramaximal double twitch interpolation, increased from 83.6 /-11.0% pre training, to 92.1  /- 7.6% post training (P < 0.05). Dorsiflexion MVC and antagonist coactivation (assessed using surface electromyography) did not change with training. Plantarflexor MVC torque normalized for triceps surae muscle volume (MVC/VOL) was 142.6  /- 32.4 kN m(-2) before training and 157.0  /- 27.9 kN m(-2) after training (a non-significant increase of 8%). No significant change in any measurement was observed in the [[CTRL]] group. This study has shown that the gain in muscle strength in response to long-term (12-month) training in older men is mostly accounted for by an increased muscle volume and activation.
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Body Composition
* Electromyography
* Exercise
* Humans
* Male
* Muscle, Skeletal

|full-text-url=https://sci-hub.do/10.1007/s00421-005-1342-3
}}
{{medline-entry
|title=Additive effect of voluntary exercise and growth hormone treatment on bone strength assessed at four different skeletal sites in an aged rat model.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/9951773
|abstract=The aim of the study was to assess the effect of growth hormone (GH), voluntary exercise (Ex), and the combination of GH and Ex on bone strength, mass, and dimensions in aged, intact female rats. In addition, the effect of food restriction (FR) was studied. Fourteen-month-old virgin F-344 rats were divided into 6 groups with 13 animals in each: (1) baseline (BSL); (2) control   solvent vehicle ([[CTRL]]); (3) GH 2.5 mg/kg/day (GH); (4) exercise, voluntary: 0.6-0.7 km/day (Ex); (5) GH treatment and voluntary exercise (GH   Ex); and (6) FR. Group 1 was killed at the beginning of the study and served as baseline. All the other groups were killed after 18 weeks' treatment. The effects of aging and treatment regimes were measured at four different skeletal sites: lumbar vertebrae, femoral cortical bone, femoral neck, and the distal femoral metaphysis. Aging in itself induced a decline in vertebral body strength and ash density. At the appendicular skeletal sites, bone mass and strength were unchanged or increased. Treatment with GH alone induced a significant increase in the biomechanical parameters at the vertebral body and the femoral diaphysis, but not at the femoral neck or the distal femoral metaphysis. Voluntary exercise on its own increased load values significantly over [[CTRL]] at the vertebral body site, but not at any of the appendicular skeletal sites. The combination of GH and voluntary exercise resulted in an additive effect at the vertebral site and at the femoral diaphysis, and a synergistic (potentiating) effect at the two femoral metaphyses. FR, on the other hand, had a negative effect on cortical bone area and strength at the femoral diaphysis, but no significant effect on the other sites tested. We conclude that GH treatment and voluntary exercise both have skeletal anabolic effects; however, these effects are exerted to differing degrees at different sites. Importantly, when dosed together, GH and Ex have either an additive or synergistic anabolic effect on all sites (axial and appendicular).
|mesh-terms=* Aging
* Animals
* Biomechanical Phenomena
* Bone Resorption
* Bone and Bones
* Disease Models, Animal
* Female
* Femur
* Food Deprivation
* Growth Hormone
* Humans
* Physical Exertion
* Rats
* Rats, Inbred F344
* Spine

|full-text-url=https://sci-hub.do/10.1016/s8756-3282(98)00169-0
}}
{{medline-entry
|title=Effects of age and live weight on fat 5 alpha-androstenone levels in young boars fed two planes of nutrition.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/3589138
|abstract=The aim of the present experiment was to determine whether age, live weight, or a combination of both, was the most important factor influencing fat 5 alpha-androstenone levels in male pigs. Three groups of 50 boars each were fed either on a liberal plane of nutrition ([[CTRL]] group) or were restricted (SW and SA groups). Fat 5 alpha-androstenone was measured three times in each pig (on biopsies at two different times and at slaughter) at either the same live weight (SW) or at the same age (SA) as [[CTRL]] boars. In addition, the genital tract was dissected at slaughter. SW boars (aged 169 days) exhibited higher fat 5 alpha-androstenone levels than [[CTRL]] boars (aged 139 days) when the first biopsy was taken at 80 kg of live weight (1.2 vs 0.8 microgram/g; P less than 0.05). By the time of the second biopsy (100 kg of live weight) and at slaughter (125 kg) there was no significant difference between the SW and [[CTRL]] groups, although the SW were 43-55 days older than the [[CTRL]]. At all three measurement times, fat 5 alpha-androstenone was lower in SA than in [[CTRL]] boars which were 21-36 kg heavier (0.5 vs 0.8 micrograms/g at 139 days; 0.9 vs 1.3 micrograms/g at 160 days; 1.2 vs 2.0 micrograms/g at 185 days; P less than 0.001). Partial correlations between fat 5 alpha-androstenone and age were significant at the first biopsy, whereas partial correlations with live weight were significant at all three times of measurement. In SA boars weighing 90 kg there was a significant correlation between fat 5 alpha-androstenone and all the developmental traits of the genital tract. In SW and [[CTRL]] pigs weighing 125 kg, fat 5 alpha-androstenone was significantly correlated with accessory sex gland development but not with testis or epididymis weight. From the present data it is concluded that both age and live weight had a significant effect on fat 5 alpha-androstenone levels in young, light boars. In older, heavier boars, age had no effect per se but live weight still had a significant influence on 5 alpha-androstenone concentrations. In boars weighing 90 kg, fat 5 alpha-androstenone level depended on sexual maturity. When the animals were sexually mature at 125 kg of live weight, 5 alpha-androstenone level depended on the individual's potentiality for steroid production, which is probably under genetic control.
|mesh-terms=* Adipose Tissue
* Aging
* Androstenes
* Animal Nutritional Physiological Phenomena
* Animals
* Biopsy
* Body Weight
* Male
* Swine

|full-text-url=https://sci-hub.do/10.1051/rnd:19870304
}}
{{medline-entry
|title=Influence of age at nutritional restriction on growth and sexual development of gilts.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/1777056
|abstract=Large White females were fed on a plane of nutrition close to ad libitum during the entire experimental period ([[CTRL]] group, n = 48) or restricted during a limited period of their growth ([[RP1]] group: 28-62 kg, [[RP2]] group: 64-96 kg, RP3 group: 97-131 kg, n = 48/group). Blood samples were taken before 200 and 230 days of age in order to detect cyclic gilts by assaying their progesterone levels. Animals were slaughtered at approximately 260 d of age and their genital tracts were examined. Overall feed intake, feed conversion ratio and daily gain were significantly lower in restricted than in [[CTRL]] gilts (average daily gain: 678, 680, 668 and 741 g/day respectively in [[RP1]], [[RP2]], RP3 and [[CTRL]] groups, P less than 0.05). At slaughter, animals from the 3 restricted groups has similar live weights but were lighter (152 vs 164 kg live weight, P less than 0.05) and leaner than [[CTRL]] (fat thickness: 29.5, 30.5, 28.0 and 34.1 mm respectively, in [[RP1]], [[RP2]], RP3 and [[CTRL]] groups). Respectively, 9, 43 and 76% of the gilts were puberal at 200, 230 and 260 days of age. The percentage of cyclic females was not influenced by treatment at 200 and 260 days of age while it was higher in [[CTRL]] (50%) and [[RP1]] (56%) groups than in [[RP2]] (35%) and RP3 (29%) groups at 230 days of age (P less than 0.05). At 260 days of age, ovarian and genital tract weights were not influenced by treatment either in prepuberal or in cyclic gilts.(ABSTRACT TRUNCATED AT 250 WORDS)
|mesh-terms=* Aging
* Animals
* Female
* Food Deprivation
* Sexual Maturation
* Swine
* Weight Gain

|full-text-url=https://sci-hub.do/10.1051/rnd:19910604
}}