UNASSIGNED: To explore the structural and functional changes in cognition-related brain regions in patients with chronic low back pain (CLBP) at earlier ages, and explore the impact of the interaction between CLBP and age on the brain.
UNASSIGNED: Seventy-six patients with CLBP were recruited and divided into \"younger\" age group (20-29 years, YA), \"middle\" age group (30-39 years, MA), and \"older\" age group (40-49 years, OA). All patients underwent functional magnetic resonance imaging (fMRI) as well as clinical psychological and pain-related symptoms assessments.
UNASSIGNED: Structural analysis showed that patients in OA group had lower gray matter (GM) volumes in the orbitofrontal cortex (OFC) bilaterally and the right superior frontal gyrus (SFG) compared to YA group. The resting-state brain activity analysis showed that amplitude of low-frequency fluctuation (ALFF) values in the bilateral postcentral gyrus and left ventral medial prefrontal cortex (mPFC) were significantly different in the OA group. The functional connectivity (FC) in the right ventral dorsolateral prefrontal cortex (DLPFC) and the right insula was significantly decreased in the OA group compared to the YA and MA groups. Likewise, the FC in the left caudal parahippocampal gyrus (PHG) and left inferior parietal lobule (IPL) were significantly lower in the MA and OA groups compared to the YA group. In addition, both the structural properties and the FC values of these brain regions were significantly correlated with age.
UNASSIGNED: This preliminary study concludes that CLBP affects the aging process. The synergistic effects of CLBP and aging accelerate the functional and structural decline of certain areas of the brain, which not only affects pain processing, but are also may be associated with cognitive declines.

Visual perception of space and time has been shown to rely on context dependency, an inferential process by which the average magnitude of a series of stimuli previously experienced acts as a prior during perception. This article aims to investigate the presence and evolution of this phenomenon in early aging. Two groups of participants belonging to two different age ranges (Young Adults: average age 28.8 years old; Older Adults: average age 62.8 years old) participated in the study performing a discrimination and a reproduction task, both in a spatial and temporal conditions. In particular, they were asked to evaluate lengths in the spatial domain and interval durations in the temporal one. Early aging resulted to be associated to a general decline of the perceptual acuity, which is particularly evident in the temporal condition. The context dependency phenomenon was preserved also during aging, maintaining similar levels as those exhibited by the younger group in both space and time perception. However, the older group showed a greater variability in context dependency among participants, perhaps due to different strategies used to face a higher uncertainty in the perceptual process.

Skeletal muscle mass and function tend to decline with increasing age. Insulin-like growth factor 1 (IGF-1) plays a key role in promoting skeletal muscle growth. Exercise improves skeletal muscle mass and function via activating the IGF-1 signaling. The aim of this study was to investigate whether different types of exercise could promote muscle hypertrophy, exercise and metabolic capacities, and activate IGF-1 signaling in early aging mice. 12-month-old male C57/BL6 mice were randomly divided into five groups: control group (CON), aerobic exercise group (AE), resistance exercise group (RE), whole-body vibration group (WBV) and electrical stimulation group (ES). Muscle weight, myofiber size, levels of IGF-1 signaling, oxidative stress, protein synthesis and degradation, and apoptosis in gastrocnemius muscle were detected. C2C12 cells were used to explore the mechanism. In this study, we confirmed that four modes of exercise increased skeletal muscle mass, exercise capacity, indicators of metabolism and protein synthesis, and inhibited oxidative stress and apoptosis via activating the IGF-1 pathway. The most effective intervention was RE. We found that WBV promoted muscle hypertrophy better than AE. Furthermore, in vitro experiment, the importance of IGF-1 / IGF-1R-PI3K / Akt signaling for maintaining skeletal muscle mass was further confirmed. AE, RE, WBV and ES increase skeletal muscle mass, exercise capacities, protein synthesis and metabolic enzyme activities, inhibit protein degradation and apoptosis in mice undergoing early aging via activating IGF-1 signaling. Among them, WBV has been shown to be significantly effective and has a similar effect of conventional exercise in promoting muscle hypertrophy.

With the exception of HIV-associated lipodystrophy, lipodystrophy syndromes are rare conditions characterized by a lack of adipose tissue, which is not generally recovered. As a consequence, an ectopic deposition of lipids frequently occurs, which usually leads to insulin resistance, atherogenic dyslipidemia, and hepatic steatosis. These disorders include certain accelerated aging syndromes or progeroid syndromes. Even though each of them has unique clinical features, most show common clinical characteristics that affect growth, skin and appendages, adipose tissue, muscle, and bone and, in some of them, life expectancy is reduced. Although the molecular bases of these Mendelian disorders are very diverse and not well known, genomic instability is frequent as a consequence of impairment of nuclear organization, chromatin structure, and DNA repair, as well as epigenetic dysregulation and mitochondrial dysfunction. In this review, the main clinical features of the lipodystrophy-associated progeroid syndromes will be described along with their causes and pathogenic mechanisms, and an attempt will be made to identify which of López-Otín\'s hallmarks of aging are present.

Intron retention (IR) is a regulatory mechanism that can retard protein production by acting at the level of mRNA processing. We recently demonstrated that IR occurs at the pre-symptomatic state during the aging process of a mouse model of aging, providing a promising biomarker for that state, and can be restored to the normal state by juzentaihoto (JTT), a Japanese herbal medicine (Kampo) (Okada et al. 2021). Here we characterized the genes that accumulate retained introns, examined the biological significance of increased IR in these genes for the host, and determined whether drugs other than JTT can have this effect. By analyzing RNA-sequencing data generated from the hippocampus of the 19-week-old SAMP8 mouse, a model for studying age-related depression and Alzheimer\'s disease, we showed that genes with increased IR are generally involved in multiple metabolic pathways and have pivotal roles in sensing homeostasis. We thus propose that IR is a stress response and works to fine-tune the expression of many downstream target genes, leading to lower levels of their translation under stress conditions. Interestingly, Kampo medicines, as well as other organic compounds, restored splicing of a specific set of retained introns in these sensor genes in accordance with the physiological recovery conditions of the host, which corresponds with the recovery of transcripts represented by differentially expressed genes. Thus, analysis of IR genes may have broad applicability in evaluating the pre-symptomatic state based on the extent of IR of selective sensor genes, opening a promising early diagnosis of any diseases and a strategy for evaluating efficacies of several drugs based on the extent of IR restoration of these sensor genes.

More than half a century of skeletal muscle research is continuing at Padua University (Italy) under the auspices of the Interdepartmental Research Centre of Myology (CIR-Myo), the European Journal of Translational Myology (EJTM) and recently also with the support of the A&CM-C Foundation for Translational Myology, Padova, Italy. The Volume 30(1), 2020 of the EJTM opens with the collection of abstracts for the conference \"2020 Padua Muscle Days: Mobility Medicine 30 years of Translational Research\". This is an international conference that will be held between March 18-21, 2020 in Euganei Hills and Padova in Italy. The abstracts are excellent examples of translational research and of the multidimensional approaches that are needed to classify and manage (in both the acute and chronic phases) diseases of Mobility that span from neurologic, metabolic and traumatic syndromes to the biological process of aging. One of the typical aim of Physical Medicine and Rehabilitation is indeed to reduce pain and increase mobility enough to enable impaired persons to walk freely, garden, and drive again. The excellent contents of this Collection of Abstracts reflect the high scientific caliber of researchers and clinicians who are eager to present their results at the PaduaMuscleDays. A series of EJTM Communications will also add to this preliminary evidence.

Objective The medical evidence supporting the efficacy of selective dorsal rhizotomy (SDR) on children with spastic diplegia is strong. However, the outcome of SDR on adults with spastic diplegia remains undetermined. The aim is to study the effectiveness and morbidities of SDR performed on adults for the treatment of spastic diplegia.  Methods Patients who received SDR in adulthood for the treatment of spastic diplegia were surveyed. The survey questionnaire addressed the living situation, education level, employment, health outcomes, postoperative changes of symptoms, changes in ambulatory function, adverse effects of SDR and orthopedic surgery after SDR.  Results The study included 64 adults, who received SDR for spastic diplegia. The age at the time of surgery was between 18 and 50 years. The age at the time of the survey was between 20 and 52 years. The follow-up period ranged from one to 28 years. The study participants reported post-SDR improvements of the quality of walking in 91%, standing in 81%, sitting in 57%, balance while walking 75%, ability to exercise in 88%, endurance in 77%, and recreational sports in 43%. Muscle and joint pain present before surgery improved in 64% after surgery. Concerning the level of ambulatory function, all patients who walked independently in all environments maintained the same level of ambulatory function. Eighteen percent of the patients who walked independently in some environments improved to the independent walking in all environments. All patients who walked with an assistive device before SDR maintained the assistive walking after SDR. Concerning adverse effects of SDR, 50% (32 of 64 patients) developed numbness in the various parts of the legs. Two patients reported a complete loss of sensation in parts of the legs, and one patient reported numbness and constant pain in the bilateral lower extremities. Ten patients (16%) reported recurrent spasticity after SDR, and three patients (5%) reported ankle clonus, which is an objective sign of spasticity. Tendon lengthening surgery after SDR was needed in 27% and hip and knee surgery in 2% and 6%, respectively.  Conclusions The great majority of our 64 patients, who received adulthood SDR for spastic diplegia, improved the quality of ambulation and abated signs of early aging. Numbness and diminished sensation in the lower extremity was the most common adverse effect of the adulthood SDR.

Tryptophan breakdown is an important mechanism in several diseases e.g. inflammation and stress-induced inflammation have been associated with the development of depression via enhanced tryptophan breakdown. Depression is a major public health problem which commonly starts during adolescence, thus identifying underlying mechanisms during early life is crucial in prevention. The aim of this work was to verify whether independent and interacting associations of psychosocial stress and inflammation on tryptophan breakdown already exist in children and adolescents as a vulnerable age group.
Two cross-sectional population-based samples of children/adolescents (8-18 y) were available: 315 from the European HELENA study and 164 from the Belgian ChiBS study. In fasting serum samples, tryptophan, kynurenine, kynurenic acid, C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-ɣ, soluble vascular adhesion molecule 1 (sVCAM1) and soluble intercellular adhesion molecule 1 (sICAM1) were measured. Psychological stress was measured by stress reports (subjective) and cortisol (objective - awakening salivary cortisol or hair cortisol). Linear regressions with stress or inflammation as predictor were adjusted for age, sex, body mass index, puberty, socio-economic status and country.
In both cohorts, inflammation as measured by higher levels of CRP, sVCAM1 and sICAM1 was associated with kynurenine/tryptophan ratio and thus enhanced tryptophan breakdown (beta: 0.145-0.429). Psychological stress was only associated with tryptophan breakdown in the presence of higher inflammatory levels (TNF-α in both populations).
Inflammatory levels were replicable key in enhancing tryptophan breakdown along the kynurenine pathway, even at young age and in a non-clinical sample. The stress-inflammation interaction indicated that only the stress exposures inducing higher inflammatory levels (or in an already existing inflammatory status) were associated with more tryptophan breakdown. This data further contributes to our understanding of pathways to disease development, and may help identifying those more likely to develop stress or inflammation-related illnesses.

The article describes the morphofunctional characteristics of erythrocytes in clinical models of early aging (essential hypertension, coronary heart disease and diabetes mellitus) by the original clinical and cytomorphological material. It is shown that in the processes of aging and early aging following effects take places: the changing of the shape and size of cells, cell-cell interactions are broken, changing the elasticity of the cell membrane is changing too and cellular destruction is promoted.
В статье на оригинальном клиническом и цитоморфологическом материале рассмотрены морфофункциональные характеристики эритроцитов в клинических моделях преждевременного старения (при эссенциальной артериальной гипертензии, ИБС и сахарном диабете). Показано, что при процессах старения и преждевременного старения происходят изменения формы и размеров клеток, нарушаются межклеточные взаимодействия, изменяется эластичность мембран клеток и активизируются процессы клеточной деструкции.

In this article, the interrelatedness of age and chronic pain is discussed and testable hypotheses about this interrelationship are postulated. Numerous studies have consistently shown mild cognitive problems, together with changes in brain gray and white matter integrity, in chronic pain patients. More recently, a handful of studies have indicated that age may play a crucial role in the reduced neurocognitive integrity in these chronic pain patients. However, studies systematically examining this interrelationship are lacking. We now give several propositions of this interaction between age and chronic pain by summarizing the evidence for the following testable hypotheses: 1) neurocognitive deficits in chronic pain are age-dependent, 2) chronic pain induces early aging, or 3) chronic pain can be considered as an age accelerator, resulting in a disproportional decline in neurocognitive integrity with increasing age. To advance this important field, it is highly recommended that future studies systematically document cognitive and neuroanatomical changes in chronic pain patients as a function of age.