Instrumental assessment of dynamic postural stability in patients with unilateral vestibular hypofunction during straight, curved, and blindfolded gait.

PURPOSE: To characterise dynamic postural stability of gait in patients with vestibular hypofunction (PwVH) using a sensor-based assessment while performing dynamic tasks and to correlate the results of this evaluation with clinical scales. METHODS: This cross-sectional study involved 22 adults between 18 and 70 years old from a healthcare hospital centre. Eleven patients suffering from chronic vestibular hypofunction (PwVH) and eleven healthy controls (HC) were evaluated through a combined inertial sensor-based and clinical scale assessment. Participants were equipped with five synchronised inertial measurement units (IMUs) (128 Hz, Opal, APDM, Portland, OR, USA): three IMUs were located on the occipital cranium bone, near the lambdoid suture of the head, at the centre of the sternum, and at L4/L5 level, just above the pelvis, and were used to quantify gait quality parameters, while the other two were located slightly above lateral malleoli and used to perform stride and step segmentation. Three different motor tasks were performed in a randomized order: the 10-m Walk Test (10mWT), the Figure of Eight Walk Test (Fo8WT) and the Fukuda Stepping Test (FST). A set of gait quality parameters related to stability, symmetry and smoothness of gait were extracted from IMU data and correlated with the clinical scale scores. PwVH and HC results were compared to test for significant between-group differences. RESULTS: Significant differences were found for the three motor tasks (10mWT, Fo8WT and FST) when comparing PwVH and HC groups. For the 10mWT and the Fo8WT, significant differences between the PwVH and HC groups were found for the stability indexes. Considering the FST, significant differences between the PwVH and HC groups were also found in the stability and symmetry of gait. A significant correlation was found between the Dizziness Handicap Inventory and gait indices during the Fo8WT. CONCLUSIONS: In this study, we characterized the dynamic postural stability alterations during linear, curved, and blindfolded walking/stepping in PwVH combining an instrumental IMU-based with traditional clinical scales approach. Combining instrumental and clinical evaluation for dynamic stability of gait alterations in PwVH is useful in thoroughly evaluating the effects of unilateral vestibular hypofunction.

Magnetic-free Extended Kalman Filter for upper limb kinematic assessment in Yoga.

Human motion analysis is gaining increased importance in several fields, from movement assessment in rehabilitation to recreational applications such as virtual coaching. Among all the technologies involved in motion capture, Magneto-Inertial Measurements Units (MIMUs) is one of the most promising due to their small dimensions and low costs. Nevertheless, their usage is strongly limited by different error sources, among which magnetic disturbances, which are particularly problematic in indoor environments. Inertial Measurement Units (IMUs) could, thus, be considered as alternative solution. Indeed, relying exclusively on accelerometers and gyroscopes, they are insensitive to magnetic disturbances. Even if the literature has started to propose few algorithms that do not take into account magnetometer input, their application is limited to robotics and aviation. The aim of the present work is to introduce a magnetic-free quaternion based Extended Kalman filter for upper limb kinematic assessment in human motion (i.e., yoga). The algorithm was tested on five expert yoga trainers during the execution of the sun salutation sequence. Joint angle estimations were compared with the ones obtained from an optoelectronic reference system by evaluating the Mean Absolute Errors (MAEs) and Pearson's correlation coefficients. The achieved worst-case was 6.17°, while the best one was 2.65° for MAEs mean values. The accuracy of the algorithm was further confirmed by the high values of the Pearson's correlation coefficients (lowest mean value of 0.86).Clinical Relevance- The proposed work validated a magnetic free algorithm for kinematic reconstruction with inertial units. It could be used as a wearable solution to track human movements in indoor environments being insensitive to magnetic disturbances, and thus could be potentially used also for rehabilitation purposes.

Muscle synergies in archery: an explorative study on experienced athletes with and without physical disability.

Archery technique requires a coordinated activation of shoulder girdle and upper extremity muscles to perform a successful shot. The analysis of muscle synergies can provide information about the motor strategy that underlies the shooting performance, also supporting the investigation of motor impairments in athletes with disability. For this purpose, electromyographic (EMG) data from five muscles were collected from a non-disabled and a W1 category Paralympic athlete, and muscle synergies were extracted from EMG envelopes using non-negative matrix factorization. Muscle synergies analysis revealed features of the motor strategy specific to the athletes' shooting technique, such as the contribution of the biceps muscle instead of the posterior deltoid during the arrow drawing and target aiming in the Paralympic athlete compared to the non-disabled athlete. It is concluded that the evaluation of the muscle synergies may be a valuable tool for exploring the motor strategies adopted by athletes with disability, providing useful information to improve athletic performance and possibly prevent the risk of injury.

Dynamic balance assessment during gait in children with Down and Prader-Willi syndromes using inertial sensors.

Down (DS) and Prader-Willi (PWS) syndromes are chromosomal disorders both characterized by obesity, ligament laxity, and hypotonia, the latter associated with gait instability. Although these shared features may justify a common rehabilitation approach, evidence exists that adults with DS and PWS adopt different postural and walking strategies. The development of an instrumented protocol able to describe these strategies and quantify patients' gait stability in the current clinical routine would be of great benefit for health professionals, allowing them to design personalized rehabilitation programs. This is particularly true for children with DS and PWS, where motor development is dramatically constrained by severe hypotonia and muscle weakness. The aim of this study was, thus, to propose an instrumented protocol, integrated with the clinical routine and based on the use of wearable inertial sensors, to assess gait stability in DS and PWS children. Fifteen children with DS, 11 children with PWS, and 12 typically developing children (CG) were involved in the study. Participants performed a 10-meter walking test while wearing four inertial sensors located at pelvis, sternum, and both distal tibiae levels. Spatiotemporal parameters (walking speed, stride frequency, and stride length) and a set of indices related to gait symmetry and upper-body stability (Root Mean Square, Attenuation Coefficient and Improved Harmonic Ratio) were estimated from pelvis and sternum accelerations. The Gross Motor Functional Measures (GMFM-88) and Intelligence Quotient (IQ Wechsler) were also assessed for each patient. A correlation analysis among the GMFM-88 and IQ scales and the estimated parameters was then performed. Children with DS and PWS exhibit reduced gait symmetry and higher accelerations at pelvis level than CG. While these accelerations are attenuated by about 40% at sternum level in CG and DS, PWS children display significant smaller attenuations, thus reporting reduced gait stability, most likely due to their typical "Trendelenburg gait". Significant correlations were found between the estimated parameters and the GMFM-88 scale when considering the whole PWS and DS group and the PWS group alone. These results promote the adoption of wearable technology in clinical routines to monitor gait patterns in children with DS and PWS: the proposed protocol allows to markedly characterize patient-specific motor limitations even when clinical assessment scores provide similar results in terms of pathology severity. This protocol could be adopted to support health professionals in designing personalized treatments that, in turn, could help improving patients' quality of life in terms of both physical and social perspectives.

Resveratrol Requires Red Wine Polyphenols for Optimum Antioxidant Activity.

OBJECTIVE: There is substantial evidence that a diet rich in fruit and vegetables may reduce the risk of aging and stress oxidative associated diseases. It has been suggested that benefits associated with fruit and red wine consumption could be due to pooled antioxidant microcomponents in diet. The aim of this study was to investigate the antioxidant activities of pure resveratrol (a well known phytoalexin, RSV) and red wine polyphenols (RWP), using UV-B radiated isolated rat hepatocytes as a model of oxidative stress. METHODS: Rat hepatocytes were isolated by the collagenase method. The cells were loaded with resveratrol and/or polyphenols at different concentrations. The production of thiobarbituric acid reactive substances (TBARS) released by UV-B radiated cells and the levels of lipid-soluble antioxidants (Dolichol, Vitamin E, Coenzyme Q9 and Q10) were measured. RESULTS: Resveratrol had pro-oxidant or antioxidant effects depending on (lower or higher) dosage. RWP protection from photolipoperoxidation was dose-dependent and increased with dosage. Combination of the two compounds exhibited synergistic antioxidant effect, and made resveratrol effective both at lower and higher dosages. CONCLUSIONS: These results suggest that resveratrol requires red wine polyphenols for optimum antioxidant activity.

A new method for the evaluation of the end-to-end distance of the knee ligaments and popliteal complex during passive knee flexion.

BACKGROUND: Accurate knowledge about the length variation of the knee ligaments (ACL, PCL, MCL and LCL) and the popliteal complex during knee flexion/extension is essential for modelling and clinical applications. The aim of the present study is to provide this information by using an original technique able to faithfully reproduce the continuous passive knee flexion-extension kinematics and to reliably identify each ligament/tendon attachment site. METHODS: Twelve lower limbs (femur, tibia, fibula, patella) were tested and set in motion (0-120°) using an ad hoc rig. Tibio-femoral kinematics was obtained using an optoelectronic system. A 3D digital model of each bone was obtained using low-dosage stereoradiography. Knee specimens were dissected and the insertion of each ligament and popliteal complex were marked with radio opaque paint. ACL, PCL and MCL were separated into two bundles. Bone epiphyses were CT-scanned to obtain a digital model of each ligament insertion. Bones and attachment site models were registered and the end-to-end distance variation of each ligament/tendon was computed over knee flexion. RESULTS: A tibial internal rotation of 18°±4° with respect to the femur was observed. The different bundles of the ACL, MCL and LCL shortened, whereas all bundles of the PCL lengthened. The popliteal complex was found to shorten until 30° of knee flexion and then to lengthen. CONCLUSION: The end-to-end distance variation of the knee ligaments and popliteal complex can be estimated during knee flexion using a robust and reliable method based on marking the ligaments/tendon insertions with radiopaque paint. LEVEL OF EVIDENCE: Level IV.

Diagnostic accuracy of endometrial thickness for the detection of intra-uterine pathologies and appropriateness of performed hysteroscopies among asymptomatic postmenopausal women.

OBJECTIVE: To measure the diagnostic accuracy of endometrial thickness for the detection of intra-uterine pathologies among asymptomatic postmenopausal women, and to test the diagnostic accuracy and appropriateness of performed hysteroscopies. STUDY DESIGN: Prospective study of 268 asymptomatic postmenopausal women with endometrial thickness ≥4 mm referred to diagnostic hysteroscopy. The diagnostic accuracy of various endometrial thickness cut-off values was tested. Histological and hysteroscopic results were compared to measure the diagnostic accuracy of outpatient hysteroscopies. RESULTS: No endometrial thickness cut-off values had optimal diagnostic accuracy [positive likelihood ratio (LR+) >10 and negative likelihood ratio (LR-) <0.1]. The best endometrial thickness cut-off value for the detection of all intra-uterine pathologies was ≥8 mm (LR+ 10.05 and LR- 0.22). An endometrial thickness cut-off value ≥10 mm did not miss any cases of endometrial cancer. The success rate of diagnostic hysteroscopy was 89%, but 97% of these revealed a benign intra-uterine pathology. The diagnostic accuracy of hysteroscopy was optimal for all intra-uterine pathologies, except endometrial hyperplasia (LR- 0.52). CONCLUSION: Using an endometrial thickness cut-off value ≥4 mm, only 3% of performed hysteroscopies were useful for the detection of pre-malignant or malignant lesions. Despite the finding that endometrial thickness did not show optimal diagnostic accuracy, using the best cut-off value (≥8 mm) may be helpful to decrease the number of false-positive results. No cases of endometrial cancer were diagnosed in asymptomatic postmenopausal women with endometrial thickness <10mm.

Development and validation of a liquid chromatography/linear ion trap mass spectrometry method for the quantitative determination of deoxynivalenol-3-glucoside in processed cereal-derived products.

Cereal-based food can be frequently contaminated by the presence of mycotoxins derived from Fusarium fungus, and, in particular, by deoxynivalenol (DON). Nowadays, analytical strategies for the detection of DON are well developed, but there are gaps for what concerns a correct identification, quantification and toxicological evaluation of the respective metabolites, mainly related to detoxifying actions via plant metabolism or to processing technologies and also referred to as "masked" mycotoxins. Here, we report the development of a liquid chromatography/linear ion trap mass spectrometry method capable of determining deoxynivalenol-3-glucoside (DON-3G), which is the main known DON metabolite, in different processed cereal-derived products. Samples were extracted with a mixture of methanol/water (80:20; v/v) and cleaned up using immunoaffinity columns. Chromatographic separation was performed using a core-shell C(18) column with an aqueous acetic acid/methanol mixture as the mobile phase under gradient conditions. The method was in-house validated on a bread matrix as follows: matrix-matched linearity (r(2)>0.99) was established in the range of 10-200 µg kg(-1); trueness expressed as recovery was close to 90%; good intermediate precision (overall RSD<9%) and adequate detection quantitation limits (4 and 11 µg kg(-1), respectively) were achieved. Furthermore, applying a metrology approach based on intralaboratory data, the estimated measurement expanded uncertainty was determined to be equal to 29%. The reliability of the method was finally demonstrated in bread, cracker, biscuit and minicake commodities, resulting in relatively low levels of DON-3G, which were not higher than 30 µg kg(-1).

Tibio-femoral joint constraints for bone pose estimation during movement using multi-body optimization.

When using skin markers and stereophotogrammetry for movement analysis, bone pose estimation may be performed using multi-body optimization with the intent of reducing the effect of soft tissue artefacts. When the joint of interest is the knee, improvement of this approach requires defining subject-specific relevant kinematic constraints. The aim of this work was to provide these constraints in the form of plausible values for the distances between origin and insertion of the main ligaments (ligament lengths), during loaded healthy knee flexion, taking into account the indeterminacies associated with landmark identification during anatomical calibration. Ligament attachment sites were identified through virtual palpation on digital bone templates. Attachments sites were estimated for six knee specimens by matching the femur and tibia templates to low-dose stereoradiography images. Movement data were obtained using stereophotogrammetry and pin markers. Relevant ligament lengths for the anterior and posterior cruciate, lateral collateral, and deep and superficial bundles of the medial collateral ligaments (ACL, PCL, LCL, MCLdeep, MCLsup) were calculated. The effect of landmark identification variability was evaluated performing a Monte Carlo simulation on the coordinates of the origin-insertion centroids. The ACL and LCL lengths were found to decrease, and the MCLdeep length to increase significantly during flexion, while variations in PCL and MCLsup length was concealed by the experimental indeterminacy. An analytical model is given that provides subject-specific plausible ligament length variations as functions of the knee flexion angle and that can be incorporated in a multi-body optimization procedure.

Fate of Fusarium mycotoxins in the cereal product supply chain: the deoxynivalenol (DON) case within industrial bread-making technology.

Fusarium mycotoxins are a relevant problem in the cereal supply chain at a worldwide level, with wheat, maize and barley being the main contaminated crops. Mould growth can happen in the pre-harvest phase and also during transport and storage due to ineffective drying conditions. Among Fusarium toxins, deoxynivalenol (DON) is considered the most important contaminant in wheat due to its widespread occurrence. In the last years the European Food Safety Authority (EFSA) and the European Commission have frequently expressed opinions on Fusarium toxins, setting limits, regulations and guidelines in order to reduce their levels in raw materials and food commodities. In particular, European legislation (Reg. 1881/2006) sets the maximum limit for DON in flour and bread as 750 and 500 microg kg(-1) respectively. Relatively few studies have taken into account the loss of trichothecenes during processing, focusing on how processing factors may influence their degradation. In particular, the description of DON behaviour during bread-making is very difficult, since complex physico-chemical modifications occur during the transformation of the raw ingredients into the final product. In the present study, we studied how DON concentration may be influenced by modifying bread-making parameters, with a special emphasis on the fermentation and baking stages, starting from a naturally contaminated flour at both pilot and industrial scales. Exploiting the power of a Design of Experiments (DoE) approach to consider the great complexity of the studied system, the obtained model shows satisfying goodness-of-fit and prediction, suggesting that the baking step (time/temperature ranges) is crucial for minimizing native DON level in bread.

Balance in patients with anorexia and bulimia nervosa.

AIM: Neuro-muscular adaptations to the loss or increase in body weight may induce postural alterations. The aim of this study was to investigate the effect of body weight alterations on postural stability in patients with anorexia nervosa and bulimia. METHODS: The study enrolled 15 women affected by anorexia nervosa (AN), (mean body mass index [BMI] 15.8+/-1.8 kg/m(2)), 15 women affected by bulimia nervosa (BN), (mean BMI 20.1+/-2.9 kg/m(2)) and 11 healthy matched women (HC), (mean BMI 20.1+/-1 kg/m(2)). Two quiet standing conditions with eyes open (EO) and closed (EC) were analysed with an optoelectronic system (Vicon 460, Viconpeak, Oxford, UK) with passive markers to estimate the centre of mass (CoM) position. RESULTS: BN patients were more unstable than HC, showing statistically significant differences in antero-posterior CoM excursions and path length. AN patients showed non significant differences from HC. Only HC showed differences between EO and EC conditions, with significantly greater excursions in medio-lateral direction in EC condition (P<0.013) as well as an increased sway area (P<0.022). CONCLUSIONS: In BN, musculoskeletal factors seem to play a major role in the diminished postural control, which appear to be linked to body weight fluctuations rather than to BMI absolute values. No clear-cut postural instability was demonstrated in patients with AN as compared to HC. Visual input appears not to affect balance in patients with eating disorders. Possible further causes of postural instability in BN and implications for rehabilitation treatment are discussed.

Factors associated with climacteric symptoms in women around menopause attending menopause clinics in Italy.

OBJECTIVE: To obtain data on correlates of climacteric symptoms in women around menopause attending menopause clinics in Italy. METHODS: Since 1997 a large cross sectional study has been conducted on the characteristics of women around menopause attending a network of first level menopause outpatient's clinics in Italy. A total of 66,501 (mean age 54.4 years) women are considered in the present paper. RESULTS: The odds ratios of moderate and severe hot flashes/night sweats were lower in more educated women and (for severe symptoms only) in women reporting regular physical activity. Depression, difficulty to sleep, forgetfulness and irritability tended to be less frequent in more educated women and (depression only) in women reporting regular physical activity. Parous women reported more frequently these symptoms. CONCLUSIONS: This large study confirms in Southern European population that low education, body mass index and low physical activity are associated with climacteric symptoms. Parous women are at greater risk of psychological symptoms.

Dietary restriction counteracts age-related changes in cholesterol metabolism in the rat.

The effects of ageing on the metabolism of cholesterol were examined in three different organs (liver, aorta and brain) of 6-, 12- and 24-month-old male Sprague-Dawley rats. Ageing was associated with a significant increase in intracellular cholesterol esters in all three organs. Steady state mRNA levels of multidrug resistance protein (MDR) and acylCoA:cholesterol acyl transferase (ACAT), enzymes involved in cholesterol import and esterification, were also increased. By contrast, expression of mRNA for neutral cholesterol ester hydrolase (nCEH) and caveolin-1, proteins involved in cholesterol ester hydrolysis and export, were significantly reduced. Dietary restriction is the only intervention shown to extend lifespan and retard age-related declines in function in mammals. To further explore the possible correlation between changes in cholesterol esterification and ageing, we analysed cholesterol metabolism in liver, aorta, and brain of aged rats exposed to two dietary restriction regimens: intermittent (alternate-day) fasting (IF) and food intake restriction (60% of ad libitum feeding). Both dietary regimens attenuated the age-related changes in cholesterol esters and in the expression of genes involved in cholesterol metabolism. These results provide evidence that distinctive age-associated changes in intracellular cholesterol metabolism occur in rats. Furthermore, these modifications can be partially reversed by dietary restriction, a condition known to affect the ageing process. Age-related changes in cholesterol metabolism may play a role in triggering and/or aggravating senescence-related disorders characterized by altered cholesterol homeostasis.

El mecanismo de prolongación de la vida por restricción calórica y la intensificación farmacológica de sus efectos / The life-prolonging mechanism of calorie restriction and the pharmacological intensification of these effects

El valor demostrativo de la estimulación de la autofagia como contribuyente al efecto de la prolongación de la vida por restricción calórica (posiblemente también la reducción insulínica, así como de la hormona de crecimiento/factor de crecimiento similar a la insulina tipo 1 y la hormesis) se revisa aquí. La autofagia es el mecanismo de reparación celular causante del mantenimiento de las membranas celulares y organelas, incluyendo peroxisomas, generadores de radicales libres y mitocondrias. Se evidencia que la administración semanal continuada de un fármaco antilipolítico puede reducir los valores de glucosa e insulina, estimular la autofagia e intensificar los efectos de la restricción calórica submáxima que conducen a la prolongación de la vida

Evidence is reviewed showing that CR (and perhaps reduced insulin of GH-IGF-1 axis and hormesis) may exhibit anti-aging effects at least partly by a stimulatory action on autophagy, the cell repair mechanism responsible for the house-keeping of cell membranes and organelles including the free radical generators peroxisomes and mitochondria. It is shown that the life-long weekly administration of an anti-lipolytic drug may decrease glucose and insulin levels and stimulate autophagy and intensify the anti-ageing effects of submaximal CR

Effects of aging and anti-aging caloric restrictions on carbonyl and heat shock protein levels and expression.

Heat shock proteins (Hsps) are induced by stressful stimuli and have been shown to protect cells and organs from such stresses both in vitro and in vivo, and play a positive role in lifespan determination. An attenuated response to stress is characteristic of senescence and no Hsp induction is observed upon exposure to stress and no protective effect of a mild stress is observed in cells from aged individuals. The artificial over-expression of Hsps, can produce a protective effect against a variety of damaging stimuli in cells from aged rats or aged humans, in whom cardiovascular disease is a major cause of morbidity in older age. Here, we show that aging significantly decreases the levels of Hsp27, Hsp60, Hsp72 and Hsc70 in right atrium and left ventricle of the rat heart, both at level of protein and of mRNA. Two different caloric restriction regimens have been found to counteract in part the decrease in the levels of Hsp expression in the aged heart tissue as well as the tendency to an increase of the levels of carbonyl in cardiac proteins. Our data suggest that cardiac Hsp levels may be a determinant of longevity in rodents, and that generation of new regimens of caloric restriction may eventually show how to improve modulation of cardiac aging.

Risk factors for type 2 diabetes in women attending menopause clinics in Italy: a cross-sectional study.

OBJECTIVE: To analyze risk factors for type 2 diabetes among women attending menopause clinics in Italy for counselling about the menopause. SUBJECTS: Women attending a network of first-level outpatient menopause clinics in Italy for general counselling about menopause or treatment of menopausal symptoms. METHODS: Cross-sectional study with no exclusion criteria. Type 2 diabetes was defined according to National Diabetes Data Groups Indications and the fasting blood glucose at an oral glucose tolerance test within the previous year. RESULTS: Out of the 44 694 considered in this analysis, 808 had a diagnosis of diabetes type 2 (1.8%). In comparison with women aged < 50 years, the multivariate odds ratios (OR) of type 2 diabetes were 1.31 (95% confidence interval (CI), 0.99-1.74) for women aged 50-52 years, 1.66 (95% CI, 1.27-2.17) at 53-56 years and 2.84 (95% CI, 2.20-3.67) in women aged > or = 57 years. Type 2 diabetes was less frequently reported in more educated women (OR high school/university vs. primary school = 0.44 (95% CI, 0.36-0.55)). Being overweight was associated with an increased risk of type 2 diabetes. In comparison with women reporting a low level of physical activity, the multivariate OR of type 2 diabetes was 0.67 (95% CI, 0.54-0.84) for women reporting regular physical activity. In comparison with premenopausal women, the multivariate OR of type 2 diabetes was 1.38 (95% CI, 1.03-1.84) in women with natural menopause. This finding was present also after allowing for the potential confounding effect of age. The multivariate OR of diabetes for users of hormonal replacement therapy was 0.58 (95% CI, 0.46-0.73). CONCLUSIONS: This large cross-sectional study suggests that postmenopausal women are at higher risk of type 2 diabetes after allowance for the effect of age. Other main determinants of risk of type 2 diabetes in women around menopause were low socioeconomic status and being overweight. Diabetes was found less frequently in those taking hormone replacement therapy.

The role of macroautophagy in the ageing process, anti-ageing intervention and age-associated diseases.

Macroautophagy is a degradation/recycling system ubiquitous in eukariotic cells, which generates nutrients during fasting under the control of amino acids and hormones, and contributes to the turnover and rejuvenation of cellular components (long-lived proteins, cytomembranes and organelles). Tight coupling between these two functions may be the weak point in cell housekeeping. Ageing denotes a post-maturational deterioration of tissues and organs with the passage of time, due to the progressive accumulation of the misfunctioning cell components because of oxidative damage and an age-dependent decline of turnover rate and housekeeping. Caloric restriction (CR) and lower insulin levels may slow down many age-dependent processes and extend lifespan. Recent evidence is reviewed showing that autophagy is involved in ageing and in the anti-ageing action of anti-ageing calorie restriction: function of autophagy declines during adulthood and is almost negligible at older age; CR prevents the age-dependent decline of autophagic proteolysis and improves the sensitivity of liver cells to stimulation of lysosomal degradation; protection of autophagic proteolysis from the age-related decline co-varies with the duration and level of anti-ageing food restriction like the effects of CR extending lifespan; the pharmacological stimulation of macroautophagy has anti-ageing effects. Besides the involvement in ageing, macroautophagy may have an essential role in the pathogenesis of many age-associated diseases. Higher protein turnover may not fully account for the anti-ageing effects of macroautophagy, and effects of macroautophagy on housekeeping of the cell organelles, antioxidant machinery of cell membranes and transmembrane cell signaling should also be considered.

Ageing and oxidative stress: a role for dolichol in the antioxidant machinery of cell membranes?

Dolichol is a polyprenol compound broadly distributed in membranes, biosynthetized by the general isoprenoid pathway from acetate via mevalonate and farnesyl pyrophosphate. Dolichol lays inside the membrane between the two leaflets of the lipid bilayer very close to the tail of phospholipid fatty acids. No definite catabolic pathways for this molecule have yet been identified. Evidence is produced that dolichol levels increase dramatically with increasing age; that anti-ageing caloric restriction retards this age-associated change; that dolichol may act as a radical scavenger of peroxidized lipids belonging to the cell membranes. In view of the polyunsaturated fatty acids (PUFA), dolichol and Vitamin E location and stechiometry, it is proposed that molecules might interact each-other to form a highly matched free-radical-transfer chain, whose malfunctioning might be involved in statin toxicity and neurodegenerative diseases.