Age-related Atrophy Research Articles

One Year Outcomes and Longitudinal Changes in Voice Improvement With Single High Dose Intracordal Trafermin Injections for Age-Related Vocal Fold Atrophy

Although intracordal trafermin injection has been performed in the treatment of age-related vocal fold atrophy, the effects of single high dose trafermin injections are unknown. In this study, we examined the 1 year outcomes and longitudinal changes in voice improvement with single high dose intracordal trafermin injections. Retrospective study with approval by our Ethics Committee. The medical records of 34 patients who underwent single high dose (50ug per side) intracordal trafermin injections under local anesthesia for vocal fold atrophy were retrospectively reviewed at 1 month pre-injection and 1 month, 6 months and 1 year post injection. Maximum phonation time (MPT), pitch range (PR), Japanese version of voice handicap index (VHI), grade of GRBAS evaluation, and jitter% improved significantly at 1-year post-injection compared to 1-month pre-injection. MPT and PR improved as early as 1-month post-injection and continued to improve most at 1-year post-injection. VHI showed negative progression from 6-months to 1-year post-injection, during which time the speaking fundamental frequency (SFF) changed to the high pitch in men. Single high dose intracordal trafermin injections can be expected to improve voice in the early post-injection period and to maintain its effect for 1 year. SFF may play a role in worsening VHI in men. level 4.

Fractal Dimension of Silhouette Magnetic Resonance Brain Images as a Measure of Age-Associated Changes in Cerebral Hemispheres

Aim: The aim of the present study was to characterize age-associated changes in the spatial configuration of cerebral hemispheres (including changes in spatial complexity and space-filling capacity) using fractal analysis of silhouette magnetic resonance brain images. Material and Methods: Magnetic resonance brain images of 100 (44 male, 56 female) participants aged between 18-86 years were studied. Five magnetic resonance images were selected from the magnetic resonance imaging dataset of each brain, including four tomographic sections in the coronal plane and one in the axial plane. Fractal dimension values of the cerebral hemispheres silhouettes were measured using the two-dimensional box-counting algorithm. Morphometric parameters based on Euclidean geometry (perimeter, area, and their derivative values) were determined as well. Results: The average fractal dimension value of the five studied tomographic sections was 1.878±0.0009, the average value of four coronal sections was 1.868±0.0010. It was shown that fractal dimension values of cerebral silhouettes for all studied tomographic sections and four coronal sections significantly decrease with age (r=-0.512, p<0.001 and r=-0.491, p<0.001, respectively). The difference in the character of age-related changes in males and females was not statistically significant. Based on the age and the fractal dimension values of the studied sample, the confidence intervals of the fractal dimension values of cerebral hemispheres silhouettes were determined, which can be used as norm criteria in clinical neuroimaging. Conclusion: The fractal analysis and obtained data can be used in neuroimaging for assessing the degree of age-related cerebral atrophy and for differentiating between normal aging and neurodegenerative diseases.

Effect of Lactobacillus curvatus HY7602-Fermented Antler on Sarcopenia in Mice

Sarcopenia, commonly found in the elderly, causes a decrease in muscle mass and function. Lactobacillus curvatus HY7602-fermented antler (FA) is a functional food that increases muscle strength and ameliorates dexamethasone-induced muscle atrophy. In the present study, we evaluated the effects of FA on age-related muscle atrophy and its mechanism of action using 100-week-old BALB/c mice. Physiological changes during fermentation were investigated. The results showed that the oral administration of FA substantially recovered muscle loss up to 23.6% and improved physical performance, such as treadmill running distance and limb grip strength, in aged mice. A gene expression analysis of muscle fibers showed that the effect of FA on age-related muscle atrophy was significantly associated with the inhibition of protein degradation and apoptosis, muscle fiber regeneration, and increased mitochondrial biogenesis. In addition, the acetate and butyrate contents increased by more than 50% during the fermentation of antler. In conclusion, FA can be considered as a functional food ingredient capable of effectively controlling muscle atrophy caused by aging and can be a novel alternative treatment for sarcopenia.

The transcription regulator ATF4 is a mediator of skeletal muscle aging

Aging slowly erodes skeletal muscle strength and mass, eventually leading to profound functional deficits and muscle atrophy. The molecular mechanisms of skeletal muscle aging are not well understood. To better understand mechanisms of muscle aging, we investigated the potential role of ATF4, a transcription regulatory protein that can rapidly promote skeletal muscle atrophy in young animals deprived of adequate nutrition or activity. To test the hypothesis that ATF4 may be involved in skeletal muscle aging, we studied fed and active muscle-specific ATF4 knockout mice (ATF4 mKO mice) at 6 months of age, when wild-type mice have achieved peak muscle mass and function, and at 22 months of age, when wild-type mice have begun to manifest age-related muscle atrophy and weakness. We found that 6-month-old ATF4 mKO mice develop normally and are phenotypically indistinguishable from 6-month-old littermate control mice. However, as ATF4 mKO mice become older, they exhibit significant protection from age-related declines in strength, muscle quality, exercise capacity, and muscle mass. Furthermore, ATF4 mKO muscles are protected from some of the transcriptional changes characteristic of normal muscle aging (repression of certain anabolic mRNAs and induction of certain senescence-associated mRNAs), and ATF4 mKO muscles exhibit altered turnover of several proteins with important roles in skeletal muscle structure and metabolism. Collectively, these data suggest ATF4 as an essential mediator of skeletal muscle aging and provide new insight into a degenerative process that impairs the health and quality of life of many older adults.

Effects of Turmeric Extract on Age-Related Skeletal Muscle Atrophy in Senescence-Accelerated Mice.

Muscle atrophy is one of the main causes of sarcopenia-the age-related loss of skeletal muscle. In this study, we investigated the effect of turmeric (Curcuma longa) extract (TE) supplementation on age-related muscle atrophy in a senescence-accelerated mouse model and explored the underlying mechanisms. Twenty-six-week-old male, senescence-accelerated mouse resistant (SAMR) mice received the AIN-93G basal diet, while twenty-six-week-old male, senescence-accelerated mouse prone 8 (SAMP8) mice received the AIN-93G basal diet or a 2% TE powder-supplemented diet for ten weeks. Our findings revealed that TE supplementation showed certain effects on ameliorating the decrease in body weight, tibialis anterior weight, and mesenteric fat tissue weight in SAMP8 mice. TE improved gene expression in the glucocorticoid receptor-FoxO signaling pathway in skeletal muscle, including redd1, klf15, foxo1, murf1, and mafbx. Furthermore, TE might have the certain potential on improving the dynamic balance between anabolic and catabolic processes by inhibiting the binding of glucocorticoid receptor or FoxO1 to the glucocorticoid response element or FoxO-binding element in the MuRF1 promoter in skeletal muscle, thereby promoting muscle mass and strength, and preventing muscle atrophy and sarcopenia prevention. Moreover, TE may have reduced mitochondrial damage and maintained cell growth and division by downregulating the mRNA expression of the genes mfn2 and tsc2. Thus, the results indicated TE's potential for preventing age-related muscle atrophy and sarcopenia.

Influence of aspirin on aging skeletal muscle: Insights from a cross-sectional cohort of septuagenarians.

Aspirin is one of the most commonly consumed cyclooxygenase (COX)-inhibitors and anti-inflammatory drugs and has been shown to block COX-produced regulators of inflammation and aging skeletal muscle size. We used propensity score matching to compare skeletal muscle characteristics of individuals from the Health ABC study that did not consume aspirin or any other COX-inhibiting drugs (non-consumers, n = 497, 74 ± 3 year, 168 ± 9 cm, 75.1 ± 13.8 kg, 33.1 ± 7.4% body fat, 37% women, 34% black) to those that consumed aspirin daily (and not any other COX-inhibiting drugs) and for at least 1 year (aspirin consumers, n = 515, 74 ± 3 year, 168 ± 9 cm, 76.2 ± 13.6 kg, 33.8 ± 7.1% body fat, 39% women, 30% black, average aspirin consumption: 6 year). Subjects were matched (p > 0.05) based on age, height, weight, % body fat, sex, and race (propensity scores: 0.33 ± 0.09 vs. 0.33 ± 0.09, p > 0.05). There was no difference between non-consumers and aspirin consumers for computed tomography-determined muscle size of the quadriceps (103.5 ± 0.9 vs. 104.9 ± 0.8 cm2 , p > 0.05) or hamstrings (54.6 ± 0.5 vs. 54.9 ± 0.5 cm2 , p > 0.05), or quadriceps muscle strength (111.1 ± 2.0 vs. 111.7 ± 2.0 Nm, p > 0.05). However, muscle attenuation (i.e., density) was higher in the aspirin consumers in the quadriceps (40.9 ± 0.3 vs. 44.4 ± 0.3 Hounsfield unit [HU], p < 0.05) and hamstrings (27.7 ± 0.4 vs. 33.2 ± 0.4 HU, p < 0.05). These cross sectional data suggest that chronic aspirin consumption does not influence age-related skeletal muscle atrophy, but does influence skeletal muscle composition in septuagenarians. Prospective longitudinal investigations remain necessary to better understand the influence of chronic COX regulation on aging skeletal muscle health.

Associations of baseline and longitudinal change in cerebellum volume with age-related changes in verbal learning and memory

The cerebellum is involved in higher-order cognitive functions, e.g., learning and memory, and is susceptible to age-related atrophy. Yet, the cerebellum's role in age-related cognitive decline remains largely unknown. We investigated cross-sectional and longitudinal associations between cerebellar volume and verbal learning and memory. Linear mixed effects models and partial correlations were used to examine the relationship between changes in cerebellum volumes (total cerebellum, cerebellum white matter [WM], cerebellum hemisphere gray matter [GM], and cerebellum vermis subregions) and changes in verbal learning and memory performance among 549 Baltimore Longitudinal Study of Aging participants (2,292 visits). All models were adjusted by baseline demographic characteristics (age, sex, race, education), and APOE e4 carrier status. In examining associations between change with change, we tested an additional model that included either hippocampal (HC), cuneus, or postcentral gyrus (PoCG) volumes to assess whether cerebellar volumes were uniquely associated with verbal learning and memory. Cross-sectionally, the association of baseline cerebellum GM and WM with baseline verbal learning and memory was age-dependent, with the oldest individuals showing the strongest association between volume and performance. Baseline volume was not significantly associated with change in learning and memory. However, analysis of associations between change in volumes and changes in verbal learning and memory showed that greater declines in verbal memory were associated with greater volume loss in cerebellum white matter, and preserved GM volume in cerebellum vermis lobules VI-VII. The association between decline in verbal memory and decline in cerebellar WM volume remained after adjustment for HC, cuneus, and PoCG volume. Our findings highlight that associations between cerebellum volume and verbal learning and memory are age-dependent and regionally specific.

Ultrasound elastography evaluation of age-related muscle atrophy: An ex vivo study

In this work, the feasibility of ultrasound elastography to evaluate age-related muscle atrophy is investigated. Ultrasound elastography is used to assess muscle stiffness alterations of bovine shoulder samples during aging treatment. Of particular interest is to investigate the decrease in muscle stiffness due to two potential reasons: (1) decrease in collagen fibers; and (2) mechanical breakdown of the muscle fascia (the soft tissue component of connective tissue surrounding muscle). Two methods of aging treatments are employed: (i) chemical treatment, and (ii) percussion treatment. Areas of the bovine shoulder samples studied, were the triceps brachii and infraspinatus. The chemically treated bovine samples demonstrated significant alterations in muscle stiffness under ultrasound in comparison to percussive treatment. The significance of these results will be discussed.

Human skeletal muscle-specific atrophy with aging: a comprehensive review.

Age-related skeletal muscle atrophy appears to be a muscle group-specific process, yet only a few specific muscles have been investigated and our understanding in this area is limited. This review provides a comprehensive summary of the available information on age-related skeletal muscle atrophy in a muscle-specific manner, nearly half of which comes from the quadriceps. Decline in muscle-specific size over ∼50 yr of aging was determined from 47 cross-sectional studies of 982 young (∼25 yr) and 1,003 old (∼75 yr) individuals and nine muscle groups: elbow extensors (-20%, -0.39%/yr), elbow flexors (-19%, -0.38%/yr), paraspinals (-24%, -0.47%/yr), psoas (-29%, -0.58%/yr), hip adductors (-13%, -0.27%/yr), hamstrings (-19%, -0.39%/yr), quadriceps (-27%, -0.53%/yr), dorsiflexors (-9%, -0.19%/yr), and triceps surae (-14%, -0.28%/yr). Muscle-specific atrophy rate was also determined for each of the subcomponent muscles in the hamstrings, quadriceps, and triceps surae. Of all the muscles included in this review, there was more than a fivefold difference between the least (-6%, -0.13%/yr, soleus) to the most (-33%, -0.66%/yr, rectus femoris) atrophying muscles. Muscle activity level, muscle fiber type, sex, and timeline of the aging process all appeared to have some influence on muscle-specific atrophy. Given the large range of muscle-specific atrophy and the large number of muscles that have not been investigated, more muscle-specific information could expand our understanding of functional deficits that develop with aging and help guide muscle-specific interventions to improve the quality of life of aging women and men.

The structural basis of age-related decline in global motion perception at fast and slow speeds

A decrease in global motion perception (GMP) has been reported in older adults, and this age-related decline in GMP varies with the speed of global motion. However, no studies have investigated whether the asynchronous age-related decline in GMP is related to degenerative changes in brain structure. In this study, the random dot kinematogram paradigm and structural magnetic resonance imaging were used to investigate the asynchronous aging of GMP at fast and slow speeds (called fast GMP and slow GMP, respectively) and their relationships with brain structure. Ninety-four older adults (65.74 ± 4.50 yrs) and 90 younger adults (22.83 ± 4.84 yrs) participated in the experiment. The results showed that older adults had higher motion coherence thresholds (MCT) than younger adults at both fast and slow speeds. Brain-behavior correlation analyses of younger adults revealed that none of the correlations between morphological measures and MCTs survived correction for multiple comparisons. For older adults, slow MCT was correlated with cortical thickness in the bilateral V4v, V5/MT+, left V7, V8, LO, and surface area in the right V7. Fast MCT was significantly correlated with gray matter volume in the right V7 and thickness in the left V5/MT+. These results support the view that global motion extraction occurs within two speed-tuned systems that are at least partially independent in terms of their neural substrates, which deteriorate with age at different speeds. Aging of GMP is also associated with morphological changes in the visual cortex. Age-related cerebral atrophy in the dorsal stream may impair both fast and slow GMP, whereas aging of the ventral stream specifically impairs slow GMP.

Three-dimensional chromatin re-organization during muscle stem cell aging.

Age-related skeletal muscle atrophy or sarcopenia is a significant societal problem that is becoming amplified as the world's population continues to increase. The regeneration of damaged skeletal muscle is mediated by muscle stem cells, but in old age muscle stem cells become functionally attenuated. The molecular mechanisms that govern muscle stem cell aging encompass changes across multiple regulatory layers and are integrated by the three-dimensional organization of the genome. To quantitatively understand how hierarchical chromatin architecture changes during muscle stem cell aging, we generated 3D chromatin conformation maps (Hi-C) and integrated these datasets with multi-omic (chromatin accessibility and transcriptome) profiles from bulk populations and single cells. We observed that muscle stem cells display static behavior at global scales of chromatin organization during aging and extensive rewiring of local contacts at finer scales that were associated with variations in transcription factor binding and aberrant gene expression. These data provide insights into genome topology as a regulator of molecular function in stem cell aging.

MRI evidence of olfactory system alterations in patients with COVID-19 and neurological symptoms.

Despite olfactory disorders being among the most common neurological complications of coronavirus disease 2019 (COVID-19), their pathogenesis has not been fully elucidated yet. Brain MR imaging is a consolidated method for evaluating olfactory system's morphological modification, but a few quantitative studies have been published so far. The aim of the study was to provide MRI evidence of olfactory system alterations in patients with COVID-19 and neurological symptoms, including olfactory dysfunction. 196 COVID-19 patients (median age: 53years, 56% females) and 39 controls (median age 55years, 49% females) were included in this cross-sectional observational study; 78 of the patients reported olfactory loss as the only neurological symptom. MRI processing was performed by ad-hoc semi-automatic processing procedures. Olfactory bulb (OB) volume was measured on T2-weighted MRI based on manual tracing and normalized to the brain volume. Olfactory tract (OT) median signal intensity was quantified on fluid attenuated inversion recovery (FLAIR) sequences, after preliminary intensity normalization. COVID-19 patients showed significantly lower left, right and total OB volumes than controls (p < 0.05). Age-related OB atrophy was found in the control but not in the patient population. No significant difference was found between patients with olfactory disorders and other neurological symptoms. Several outliers with abnormally high OT FLAIR signal intensity were found in the patient group. Brain MRI findings demonstrated OB damage in COVID-19 patients with neurological complications. Future longitudinal studies are needed to clarify the transient or permanent nature of OB atrophy in COVID-19 pathology.

Caloric restriction delays age-related muscle atrophy by inhibiting 11β-HSD1 to promote the differentiation of muscle stem cells.

Calorie restriction (CR) is an important direction for the delay of sarcopenia in elderly individuals. However, the specific mechanisms of CR against aging are still unclear. In this study, we used a CR model of elderly mice with muscle-specific 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) knockout mice and 11β-HSD1 overexpression mice to confirm that CR can delay muscle aging by inhibiting 11β-HSD1 which can transform inactive GC(cortisone) into active GC(cortisol). The ability of self-proliferation and differentiation into muscle fibers of these mouse muscle stem cells (MuSCs) was observed in vitro. Additionally, the mitochondrial function and mitochondrial ATP production capacity of MuSCs were measured by mitochondrial oxygen consumption. It was found that the 11β-HSD1 expression level was increased in age-related muscle atrophy. Overexpression of 11β-HSD1 led to muscle atrophy in young mice, and 11β-HSD1 knockout rescued age-related muscle atrophy. Moreover, CR in aged mice reduced the local effective concentration of glucocorticoid (GC) through 11β-HSD1, thereby promoting the mitochondrial function and differentiation ability of MuSCs. Together, our findings highlight promising sarcopenia protection with 40% CR in older ages. Furthermore, we speculated that targeting an 11β-HSD1-dependent metabolic pathway may represent a novel strategy for developing therapeutics against age-related muscle atrophy.

Fine-grained age-matching improves atrophy-based detection of mild cognitive impairment more than amyloid-negative reference subjects

IntroductionIn clinical practice, differentiating between age-related gray matter (GM) atrophy and neurodegeneration-related atrophy at early disease stages, such as mild cognitive impairment (MCI), remains challenging. We hypothesized that fined-grained adjustment for age effects and using amyloid-negative reference subjects could increase classification accuracy. MethodsT1-weighted magnetic resonance imaging (MRI) data of 131 cognitively normal (CN) individuals and 91 patients with MCI from the Alzheimer’s disease neuroimaging initiative (ADNI) characterized concerning amyloid status, as well as 19 CN individuals and 19 MCI patients from an independent validation sample were segmented, spatially normalized and analyzed in the framework of voxel-based morphometry (VBM). For each participant, statistical maps of GM atrophy were computed as the deviation from the GM of CN reference groups at the voxel level. CN reference groups composed with different degrees of age-matching, and mixed and strictly amyloid-negative CN reference groups were examined regarding their effect on the accuracy in distinguishing between CN and MCI. Furthermore, the effects of spatial smoothing and atrophy threshold were assessed. ResultsApproaches with a specific reference group for each age significantly outperformed all other age-adjustment strategies with a maximum area under the curve of 1.0 in the ADNI sample and 0.985 in the validation sample. Accounting for age in a regression-based approach improved classification accuracy over that of a single CN reference group in the age range of the patient sample. Using strictly amyloid-negative reference groups improved classification accuracy only when age was not considered. ConclusionOur results demonstrate that VBM can differentiate between age-related and MCI-associated atrophy with high accuracy. Crucially, age-specific reference groups significantly increased accuracy, more so than regression-based approaches and using amyloid-negative reference groups.

Approach to acute psychosis in older adults.

Approach to acute psychosis in older adults.

METABOLOMIC SIGNATURES OF BRAIN ATROPHY PATTERNS IN AGING AND ALZHEIMER'S DISEASE

Abstract Can plasma metabolomics reveal mechanisms of brain aging? We investigated metabolomic signatures of brain atrophy patterns related to cognitive decline and Alzheimer’s disease(AD) risk. Relationships between metabolomics(Biocrates-p500) and annual rates of change in two neuroimaging-based brain atrophy patterns(SPARE-BA indexing brain aging, SPARE-AD indexing AD-related atrophy) were examined using multivariable linear regression in 477 Baltimore Longitudinal Study of Aging participants aged 60+, adjusted for demographic variables and BMI. Higher concentrations of sarcosine, triglycerides, diglycerides, and ceramides and lower concentrations from phosphatidylcholines and cholesteryl ester were associated with faster rates of SPARE-BA increase longitudinally. Higher concentrations of diglyceride and alpha-amino-butyric acid and lower concentrations of tryptophan, hippuric acid, cholesteryl ester, phosphatidylcholine and sphingomyelin were associated with faster rates of SPARE-AD. Metabolites have differential associations with age-related and AD-related brain atrophy patterns, which may provide new insights into preventive and therapeutic interventions. Future studies should examine whether metabolite changes precede brain atrophy patterns.

INFLUENCE OF ASPIRIN ON AGING SKELETAL MUSCLE SIZE

Abstract Aspirin is one of the most commonly consumed cyclooxygenase (COX)-inhibitors and anti-inflammatory drugs and may provide insight into the control of age-related skeletal muscle atrophy. This investigation compared skeletal muscle size (via computed tomography) of older individuals from the Health ABC study that did not consume aspirin or any other COX-inhibiting drug (non-consumers; n=1,155, 74±3y, 48% women, 45% black) to those that consumed aspirin daily (and not any other COX-inhibiting drug) and for at least one year (aspirin consumers; n=515, 74±3y, 39% women, 30% black, average aspirin consumption: 6y). In white and black men, the long-term aspirin consumers had significantly larger quadriceps muscle size compared to non-consumers (p &amp;lt; 0.05). In white men only, these differences were influenced by age (p &amp;lt; 0.05). In white and black women, quadriceps muscle size was not different between the aspirin consumers and non-consumers (p&amp;gt;0.05). In men and women of either race, there was no hamstrings muscle size difference between the aspirin consumers and non-consumers (p&amp;gt;0.05). These data suggest that long-term regulation of the COX pathway with the common over-the-counter drug aspirin may impact aging muscle mass in a sex and muscle group specific fashion, which is supported by previous mechanistic human and animal studies.

Changes in hippocampal volume during a preceding 10-year period do not correlate with cognitive performance and hippocampal blood‒brain barrier permeability in cognitively normal late-middle-aged men

Hippocampal blood–brain barrier (BBB) permeability may increase in normal healthy ageing and contribute to neurodegenerative disease. To examine this hypothesis, we investigated the correlation between blood–brain barrier (BBB) permeability, regional brain volume, memory functions and health and lifestyle factors in The Metropolit 1953 Danish Male Birth Cohort. We used dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with a gadolinium-based contrast agent to assess BBB permeability in 77 participants in the cohort. BBB permeability was measured as Ki values in the hippocampus, thalamus and white matter. Over a 10-year period, we observed progressive atrophy of both the left and right hippocampus (p = 0.001). There was no significant correlation between current BBB permeability and hippocampal volume, prior atrophy or cognition. The hippocampus volume ratio was associated with better visual and verbal memory scores (p < 0.01). Regional BBB differences revealed higher Ki values in the hippocampus and white matter than in the thalamus (p < 0.001). Participants diagnosed with type II diabetes had significantly higher BBB permeability in the white matter (p = 0.015) and thalamus (p = 0.016), which was associated with a higher Fazekas score (p = 0.024). We do not find evidence that BBB integrity is correlated with age-related hippocampal atrophy or cognitive functions. The association between diabetes, white matter hyperintensities and increased BBB permeability is consistent with the idea that cerebrovascular disease compromises BBB integrity. Our findings suggest that the hippocampus is particularly prone to age-related atrophy, which may explain some of the cognitive changes that accompany older age, but this prior atrophy is not correlated with current BBB permeability.

Adiponectin receptors activation performs dual effects on regulating myogenesis and adipogenesis of young and aged muscle satellite cells.

Skeletal muscle mass and function deteriorate with ageing. Adiponectin receptors (APNrs), mainly activated by adiponectin, participate in various physiological activities and have varying signalling pathways at different ages. This study aimed to explore whether discrepant performance exists in APNr activation regulating young and aged muscle satellite cells (MUSCs) and whether age-related muscle dysfunction could be alleviated upon APNr activation. The gastrocnemius muscle phenotype was observed in male mice aged 2 and 18 months. An APNr agonist (AdipoRon) was used in vitro and in vivo to investigate the changes in cell biological behaviours and whether muscle dysfunction could be retarded after APNr activation. Aged mice exhibited decreased muscle mass and increased fat infiltration. APNr activation inhibited C2C12 cells and young MUSCs (YMUSCs) proliferation but showed no obvious effect on aged MUSCs (AMUSCs). Moreover, APNr activation inhibited the migration of both YMUSCs and AMUSCs. Interestingly, APNr activation hampered the myogenic differentiation but advanced the adipogenic differentiation of YMUSCs, yet exact opposite results were presented in AMUSCs. It was demonstrated that Wnt and PI3K signalling pathways may mediate the phenotypic differences. Furthermore, in vivo experiments verified that APNr activation ameliorated age-related muscle atrophy and excessive fat infiltration. APNr activation exerted dual effects on the regulation of myogenesis and adipogenesis of YMUSCs and AMUSCs and rescued age-related skeletal muscle dysfunction.

The Underreporting of Age-related Geographic Atrophy of the Macula See Editorial on page 287.

The Underreporting of Age-related Geographic Atrophy of the Macula See Editorial on page 287.