Normal Aging Process Research Articles

A single dose of lipopolysaccharide elicits autofluorescence in the mouse brain.

One hallmark of aging is autofluorescence (AF) in the brain. However, the underlying mechanism for inducing AF remains unknown. This study aims to determine the cause(s) of this phenomenon. The endogenous expression pattern of AF in mice was examined at differing ages. Intraperitoneal injection of a single dose of lipopolysaccharide (LPS) was performed to induce AF. Copper sulfate was applied to remove AF to allow for further immunofluorescence staining. AF appeared in the mouse brain as early as 3 months of age. In the cortex, AF occurs in the lysosomes of microglia, astrocytes, endothelial cells, and oligodendrocyte lineage cells and its prevalence increases with age. Interestingly, AF never occurs in the pericytes of young or aged brains. LPS administration resulted in a rapid and marked induction of brain AF, similar to the normal aging process. Finally, age-related and induced AF can be eliminated by low concentrations of copper sulfate solution. This pre-treatment is safe for aging and lineage tracing studies. These findings depict that AF in the brain could be associated with the innate immune response against Gram-negative bacteria infection.

Incidence of cognitive impairment after hypothetical interventions on depression, nighttime sleep duration, and leisure activity engagement among older Chinese adults: An application of the parametric g-formula.

Cognitive impairment is an age-relevant intermediate stage where cognition declines to a state between the normal aging process and dementia. Earlier studies reported that depression, inappropriate nighttime sleep duration (NSD), and limited leisure activity engagement are cognitive impairment risk factors among older adults. Thus, we postulated that interventions on depression, sleep duration, and leisure activity engagement can reduce cognitive impairment risk. However, no earlier research ever explored this. The data of 4,819 respondents aged 60 years and above, without cognitive impairment at baseline and with no prior history of memory-related diseases, including Alzheimer's disease, Parkinson's disease, and encephalatrophy, were obtained from the China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2018. The parametric g-formula, an analytic tool for estimating standardized outcome distributions using covariate (exposure and confounders)-specific estimates of the outcome distribution, was used to estimate 7-year cumulative cognitive impairment risks among older Chinese adults, under independent hypothetical interventions on depression, NSD, and leisure activity engagement, which was subdivided into social activity (SA) and intellectual activity (IA) for the different intervention combinations. The observed cognitive impairment risk was 37.52%. Independent intervention on IA was the most effective factor in reducing incident cognitive impairment, with a risk ratio (RR) of 0.75 (95% confidence interval [CI]: 0.67-0.82), followed by depression (RR: 0.89, 95% CI: 0.85-0.93) and NSD (RR: 0.88, 95% CI: 0.80-0.95). The joint intervention combining depression, NSD, and IA interventions could reduce the risk by 17.11%, with an RR of 0.56 (95% CI: 0.48-0.65). In subgroup analyses, independent interventions on depression and IA had analogously significant effects on men and women. However, interventions on depression and IA had stronger effects on literate than illiterate individuals. Hypothetical interventions on depression, NSD, and IA reduced cognitive impairment risks among older Chinese adults, both independently and jointly. The findings of the present study suggest that the intervention measures on depression, inappropriate NSD, limited intellectual activities, and their combination may prove to be effective strategies for preventing cognitive impairment among older adults.

Crosstalk between Adipose Tissue and Hepatic Mitochondria in the Development of the Inflammation and Liver Injury during Ageing in High-Fat Diet Fed Rats.

Obesity is considered an epidemic disorder, due to an imbalance between energy consumption and metabolizable energy intake. This balance is increasingly disrupted during normal aging processes due to the progressive impairment of mechanisms that normally control energy homeostasis. Obesity is triggered by an excessive lipid depots but reflects systemic inflammation along with large adipocytes secreting proinflammatory adipokines, an increase of the free fatty acids levels in the bloodstream, and ectopic lipid accumulation. Hepatic fat accumulation is the most common cause of chronic liver disease, characterized by mitochondrial dysfunction with a consequent impaired fat metabolism and increased oxidative stress. Therefore, mitochondrial dysfunction is associated to hepatic lipid accumulation and related complications. In this study, we assessed the crosstalk between adipose tissue and liver, analyzing the time-course of changes in hepatic mitochondrial fatty acid oxidation capacity versus fatty acid storage, focusing on the contribution of adipose tissue inflammation to hepatic lipid accumulation, using a rodent model of high fat diet-induced obesity. Our results demonstrate that both high-fat diet-induced obesity and aging induce dysregulation of adipose tissue function and similar metabolic alterations mediated by mitochondrial function impairment and altered inflammatory profile. The high fat diet-induced obesity anticipates and exacerbates liver mitochondrial dysfunction that occurs with aging processes.

Prelimbic Cortical Stimulation with L-methionine Enhances Cognition through Hippocampal DNA Methylation and Neuroplasticity Mechanisms.

Declining global DNA methylation and cognitive impairment are reported to occur in the normal aging process. It is not known if DNA methylation plays a role in the efficacy of memory-enhancing therapies. In this study, aged animals were administered prelimbic cortical deep brain stimulation (PrL DBS) and/or L-methionine (MET) treatment. We found that PrL DBS and MET (MET-PrL DBS) co-administration resulted in hippocampal-dependent spatial memory enhancements in aged animals. Molecular data suggested MET-PrL DBS induced DNA methyltransferase DNMT3a-dependent methylation, robust synergistic upregulation of neuroplasticity-related genes, and simultaneous inhibition of the memory-suppressing gene calcineurin in the hippocampus. We further found that MET-PrL DBS also activated the PKA-CaMKIIα-BDNF pathway, increased hippocampal neurogenesis, and enhanced dopaminergic and serotonergic neurotransmission. We next inhibited the activity of DNA methyltransferase (DNMT) by RG108 infusion in the hippocampus of young animals to establish a causal relationship between DNMT activity and the effects of PrL DBS. Hippocampal DNMT inhibition in young animals was sufficient to recapitulate the behavioral deficits observed in aged animals and abolished the memory-enhancing and molecular effects of PrL DBS. Our findings implicate hippocampal DNMT as a therapeutic target for PrL DBS and pave way for the potential use of non-invasive neuromodulation modalities against dementia.

Pancreatic changes with lifestyle and age: What is normal and what is concerning?

During the aging process, typical morphological changes occur in the pancreas, which leads to a specific "patchy lobular fibrosis in the elderly." The aging process in the pancreas is associated with changes in volume, dimensions, contour, and increasing intrapancreatic fat deposition. Typical changes are seen in ultrasonography, computed tomography, endosonography, and magnetic resonance imaging. Typical age-related changes must be distinguished from lifestyle-related changes. Obesity, high body mass index, and metabolic syndrome also lead to fatty infiltration of the pancreas. In the present article, age-related changes in morphology and imaging are discussed. Particular attention is given to the sonographic verification of fatty infiltration of the pancreas. Ultrasonography is a widely used screening examination method. It is important to acknowledge the features of the normal aging processes and not to interpret them as pathological findings. Reference is made to the uneven fatty infiltration of the pancreas. The differential diagnostic and the differentiation from other processes and diseases leading to fatty infiltration of the pancreas are discussed.

Aging Effects on Perceptual Reading Span: Evidence from an Eye-Tracking Study

Objectives: The purpose of this study was to investigate how aging influences the perceptual span and reading through online reading measurement variables using an eye-tracking paradigm. Methods: This study had a total of 38 participants including 20 normal younger and 18 older adults. Offline (reading comprehension accuracy) and online (words per second, mean fixation duration) measurement variables were analyzed through sentence comprehension questions and perceptual span measurement tasks. Results: 1) There were not significant differences between the older adults and younger adults in reading comprehension accuracy. There was no cognitive demand due to the low difficulty of the task, and it did not affect the reading comprehension accuracy of each group. 2) There were significant differences between the older adults and younger adults in both words per second and mean fixation duration. The older group showed a decrease in encoding ability due to the normal aging process. Additionally, the performance of words per second and mean fixation duration was significantly lower under the one fixated word condition (1W) in both groups. 3) In the case of mean fixation duration, the older group fixed their gaze longer than the younger. The older group showed greater difficulty under the 1W condition when the cognitive load was increased by presenting limited language information. Conclusion: This study was intended to examine the perceptual span of older adults and the level which shows the aging-effect concretely. It was possible to predict that the perceptual span of the younger group was between one or two words to the right of the fixated word (W+1 and W+2), and that of the elderly was W+1.

Srinivaspura Aging, Neuro Senescence and COGnition (SANSCOG) study: Study protocol.

Prospective, population-based, aging, and cognition studies are an important approach to understand normal and pathological aging processes. This is a longitudinal, community-based cohort study (n = 10,000) in rural India, with long-term follow-up for comprehensive evaluation of risk and protective factors associated with cognitive changes during aging. All participants will undergo comprehensive clinical, neurocognitive, and biochemical assessments. Genotyping using genome-wide association studies will be done for all participants. Whole genome sequencing and brain imaging (magnetic resonance imaging) will be done in a subset. This study will generate a rich database of clinical, neurocognitive, biochemical, neuroimaging, and genetic data that can help identify risk and protective factors for dementia and other related disorders. This longitudinal study is first of its kind, involving comprehensive evaluations, spanning phenotype to genotype, in a rural Indian cohort, and has major public health implications.

Transconjunctival Blepharoplasty: An Overview

Lower lid blepharoplasty is becoming an increasing popular cosmetic surgery to create a more youthful effect around the eyes. As the normal ageing process takes place this can affect the periorbital region giving the appearance of puffy eyes with dark circles. The transconjunctival approach allows this problem to be rectified without making any external skin incision, allowing for a scar free approach. This has led it to it becoming an increasingly sought-after surgery.

An Analysis of the Contributors and Factors Influencing Dietary Patterns Among the Elderly Population

The normal process of aging consists of numerous behavioral, social, physical, psychological, and socioeconomic factors which may negatively affect the nutritional status of a senior. Old people are susceptible to poor nutritional status as they are mostly affected by nutritional deficiencies compared to individuals that belong to other age groups. The poor dietary pattern among the elderly leads to chronic diseases such as coronary heart disease, atherosclerosis, type 2 diabetes, hypertension, or malnutrition. Factors such as socioeconomic indicators, price of food items, marital status, psychological factors, changes in sensory functioning, access to food commodities, nutrition knowledge and cooking skills, gastrointestinal problems, oral health, and medication factors may influence the dietary pattern of an elderly individual. This review focuses on the factors affecting the eating habits of the elderly.

A QUALITATIVE STUDY EXPLORING OLDER ADULTS’ PERCEPTIONS, FACILITATORS, AND BARRIERS IN PLANNING FOR AGING AND FRAILTY

Abstract Aging in place is often a desired aspect of the aging trajectory but too often older adults and society in general, do not consider the factors involved in planning to make this a reality. Planning for aging and frailty entails a comprehensive life course approach to planning for one’s aging process in five unique domains: communication/socialization, environmental, financial, physical care, and cognitive status. In order to promote upstream planning, there is a need to explore the lived experiences of older adults through understanding their viewpoints on planning, and what may promote or hinder this process. The purpose of this study was to explore how people perceive the concept of planning for aging and frailty and to identify facilitators and barriers involved in planning efforts. Using semi-structured questions, 20 community-dwelling older adults (aged 50-80) were interviewed. In-vivo coding and descriptive content analysis was utilized and revealed 17 codes within categories, including six codes and three categories in the perception domain (internal, external, future-oriented), seven codes and three categories in the facilitators domain (internal, external, systems), and four codes and two categories in the barriers domain (internal, systems). The depth of older adults’ personal identities, life experiences, and the impact of societal influences emerged within the categories. Planning for aging and frailty is an unique concept that promotes planning through awareness and acceptance of the normal aging process. Future research through intervention development is needed to educate and empower older adults, optimize planning, and navigate barriers to planning.

DNA Methylation: An Approach to Forensic Age Prediction by Molecular Mechanism

Epigenetic processes have an important role in gene expression which is affected by living environments conditions. Occurrence of epigenetics is conciliated by two major molecular mechanisms which includes histone modification and DNA methylation. DNA methylation is an epigenetic channel action, this is a natural process where transmission of a methyl group on the C5 position of the cytosine to form 5-methylcytosine at genome. So, epigenetic change is normal and continual fact that may be influenced by many factors including age, the environment / lifestyle, and disease state. The normal process of aging causes a span of transformation of tissues and organs which gathered over life time. Now this could be possible to be examined through molecular based method. In view of this methylation levels of age associated marker have been used for highly accurate age prediction in this area and depicted that an age associated methylation marker on specific gene location found to be useful with marginal lapse. In Indian scenario there are no such study published on epigenetic markers for age estimation. In future for forensic cases work Molecular biomarkers may be significant to estimate age.

Naming as a window to word retrieval changes in healthy and pathological ageing: Methodological considerations.

Word retrieval skills change across the lifespan. Permanent alterations in the form of decreased accuracy or increased response time can be a consequence of both normal ageing processes or the presence of acquired and neurodegenerative disorders (e.g., aphasia and dementia). Despite the extensive literature exploring the neuroanatomical underpinnings of word retrieval, psycholinguistic, biolinguistic and theoretical explanations, and the vast amount of evidence from primary and secondary language disorders, the best approach to consistently capture these changes is yet to be discovered. The goal of this paper is to determine which method(s) stand(s) as the most suitable candidate(s) to provide an accurate picture of word retrieval in the oral production of different groups of adult speakers, including cases of healthy ageing, preclinical Alzheimer's disease (AD), mild cognitive impairment (MCI), aphasia and dementia. Using an integrative review of recent peer-reviewed journal articles, we provide an overview of the different behavioural methods traditionally used to measure oral naming skills in research-oriented and clinical protocols and discuss their main advantages and limitations. Most existing studies are based on the results of people with diagnosed language disorders. Despite the growing interest, the reliability of the majority of the tasks to detect subtle changes associated with healthy ageing, MCI and preclinical AD are yet to be demonstrated, and the delicate balance between informativeness and efficiency (especially in terms of administration time and variable control) in experimental protocols is yet to be achieved. In this article we propose the pursuit of an integrative overarching methodology to characterize all naming deficits (from anecdotal to permanent) and all adult populations (from healthy to pathological ageing). A combination of spontaneous speech data and results from structured tasks stands as the best approach to capture changes in word retrieval skills of adult speakers with and without observable deficits. This review can guide future reflections on the necessary prerequisites of purpose-oriented, sensitive and reliable protocols for the detection of incipient word retrieval problems, thus contributing to the early diagnosis and the design of personalized multicomponent treatments. What is already known on this subject Word retrieval skills change during adulthood as a consequence of the neurological degradation associated with ageing. These changes are more dramatic in the event of acquired and neurodegenerative disorders. Numerous studies based on people with observable language disorders have addressed the multiplicity of factors involved in word retrieval and provided evidence of potential loci of impairment from a neuroanatomical, cognitive and/or (psycho-)linguistic perspective. What this paper adds to existing knowledge This study focuses on methodological strategies to assess naming skills and provides a reflection on generally accepted good practices and unresolved challenges to inform task selection, emphasizing the necessity for a combination of methods to best capture the actual problems and needs of people confronting word retrieval difficulties in their daily lives. Task selection, variable control and administration time stand as key concepts to adjust to the requirements of research and clinical contexts. What are the potential or actual clinical implications of this work? The results of this review can orient future research towards the creation of sensitive, reliable and (ecologically) valid materials for the (early) detection of word retrieval deficits and for the customization of treatment protocols to alleviate or palliate their effects.

Socio-health seeking profile of women in Post Menopausal Age group: A study in a Rural block of Ganjam district, South Odisha

Background: Menopause is defined as” the time when there has been no menstrual periods for 12 consecutive months and no other biological or physiological cause can be identified.” Objectives: 1) To describe the socio-demographic characteristics of post menopausal women in study area. 2) To explore out the various factors related to the age at menopause. 3) To assess the health seeking behaviour of study population. Materials and Methods- This study was a cross sectional community based observational study which was carried out among Postmenopausal women in 8 selected villages of Chhatrapur block of Ganjam district, Odisha for a period from October 2016 to September 2018 with a sample size of 247. Results- In the present study, 39.3% of the study population attained menopause at the age 46-50 years and 11.7% at the age 51-55years. Factors like socioeconomic status, age at menarche ,parity ,marital status , addiction status, family history of early menopause ,BMI and contraception user were found to have statistical significant association with the age at menopause. On logistic regression by adjusting all the variables it was found that age of study population [AOR=3.030 (1.639-5.602), educational qualification[AOR=11.798 (4.002-34.777)], and occupation [AOR= 3.913 (1.296-11.82)] were found to be significantly associated with the health seeking behaviour. Conclusion-In the present study the mean age at menopause was 46.98±4.080 years. Majority of postmenopausal women perceived that menopause occurred due to normal process of ageing. But less than half of the respondents sought treatment because of lack of knowledge about the symptoms and availability of treatment modalities. Awareness and knowledge about all the aspects of menopause should be provided to them through the health workers and women organisation. Keywords: Behaviour, Health seeking, Menopause, Postmenopausal women.

Alleviating the Menopausal Journey with Black Cohosh

Menopause may be one of the most intimidating life phase and a natural inevitable change for a woman. By 2030, there will be more than 1.2 billion menopausal women in the world [1]. Approximately four out of five women experience MPS, including MPS brought on by surgery, chemotherapy, or pelvic radiation. A small percentage of women experience this normal ageing process asymptomatically. The wellbeing and quality of life of these women is greatly impacted by the severe and disabling symptoms that between 50 and 85% of these women worldwide experience [1-3]. Women frequently have hot flashes during the period of attaining menopause. The episodes normally last between 30 and 10 minutes and might be accompanied by shivering, perspiration, and skin reddening. Other signs include be mood swings, sleep issues, and vaginal dryness. Each woman's symptoms are different in intensity. Early menopause is defined as the onset of menopause before the age of 45. Along with symptoms like hot flashes and night sweats, mood swings, arthralgia, and vaginal dryness, menopause has physical side effects include bone loss, an increase in belly fat, and negative changes to a woman's lipid profile.

Assessing BDNF correlations with non-invasive indicators of neurological decline in different age groups

Background: Health is the prime concern of the modern world, and with the increasing life span, both the physical and mental health of human being decline, eventually affecting the cognitive abilities of a person, which may be due to normal aging processes or neuropathological reasons. A cross-sectional study investigated the relationship between BDNF level, neurological disturbance, and aging.
 Methodology: Cognitive assessment is done through verbal fluency test (FAS, DSST, and 6CIT) and BDNF level in blood found through HPLC utilizing the ALIZA kit method.
 Results: Descriptive statistics were applied for continuous variables. Hence, one-way ANOVA was performed to show the relationship between cognitive parameters and aging.
 Conclusion: Our study reports that verbal fluency disturbs as lifetime increases, although sex, education, obesity, or lifestyle does not affect cognition.

A multimodal pilot study of default mode network (DMN) connectivity across the lifespan in healthy volunteers using functional imaging, CSF, and plasma Alzheimer's disease biomarkers

AbstractBackgroundNormal aging is associated with decreased functional connectivity (FC) in the brain’s default mode network (DMN). Additionally, cerebral burden of both amyloid‐β (Aβ) and tau proteins further contribute to decreased DMN FC in the course of the normal aging process (Wales and Leung, 2021). However, the current literature is sparse and unclear as to the independent actions of Aβand tau on FC of DMN, with tau being associated with general hypoconnectivity (Wales and Leung, 2021). The current pilot study examines resting state fMRI (rsfMRI) data in conjunction with Alzheimer’s Amyloid/Tau/Neurodegeneration (ATN) biofluid biomarkers in healthy individuals, using the isthmus cingulate of the retrosplenial cortex as seed for FC analysis of the DMN.MethodrsfMRI scans are collected in the LifeSPAN Biobanking project [ongoing]. Scans are preprocessed utilizing standard FreeSurfer pipeline. Standard parcellations are assigned using the Desikan‐Killiany atlas. In initial analyses, isthmus cingulate served as the seed for DMN analysis using the FSFAST processing stream within FreeSurfer. ATN biomarkers are obtained from cerebrospinal fluid (CSF) and the following biomarker ratios were computed: Aβ42/Aβ40 (Aβ ratio) and phosphorylated tau‐181 (pTau181) / total Tau (tTau) (pTau181/tTau ratio).ResultIn the initial 14 participants (aged 26‐82 years) [Table 1], General Linear Models (GLMs), adjusted for age, were utilized to evaluate the associations between DMN FC and the following AD biomarkers: Aβ40, Aβ42, Aβ ratio, tTau, pTau181, and pTau181/tTau ratio [Table 2; Figure 1]. After correcting for multiple comparisons (p<0.05), significant association between tTau, and the FC between the DMN and the right inferior temporal region was observed [Table 3].ConclusionThe pilot analysis indicates at least tTau has an association with DMN FC, but sample size precludes conclusion or interpretation. Preliminary data obtained in this exploratory analysis provides a framework for examining the effect of AD biomarkers on the DMN and other functional networks. Future research will incorporate synaptic, inflammatory and other markers into similar statistical models and report preliminary associations. Reference Wales R, Leung H‐C. The Effects of Amyloid and Tau on Functional Network Connectivity in Older Populations. Brain. 2021;142(8):2483‐2491. doi:10.1093/brain/awz162

The APOE locus is linked to decline in general cognitive function: 20-years follow-up in the Doetinchem Cohort Study

Cognitive decline is part of the normal aging process. However, some people experience a more rapid decline than others due to environmental and genetic factors. Numerous single nucleotide polymorphisms (SNPs) have been linked to cognitive function, but only a few to cognitive decline. To understand whether cognitive function and cognitive decline are driven by the same mechanisms, we investigated whether 433 SNPs previously linked to cognitive function and 2 SNPs previously linked to cognitive decline are associated with both general cognitive functioning at baseline and general cognitive decline up to 20-years follow-up in the Doetinchem Cohort Study (DCS). The DCS is a longitudinal population-based study that enrolled men and women aged 20–59 years between 1987–1991, with follow-up examinations every 5 years. We used data of rounds 2–6 (1993–2017, n = 2559). General cognitive function was assessed using four cognition tests measuring memory, speed, fluency and flexibility. With these test scores, standardized residuals (adjusted for sex, age and examination round) were calculated for each cognition test at each round and subsequently combined into one general cognitive function measure using principal component analyses. None of the 435 previously identified variants were associated with baseline general cognitive function in the DCS. But rs429358-C, a coding apolipoprotein E (APOE) SNP and one of the variants previously associated with cognitive decline, was associated with general cognitive decline in our study as well (p-value = 1 × 10−5, Beta = −0.013). These findings suggest that decline of general cognitive function is influenced by other mechanisms than those that are involved in the regulation of general cognitive function.

Effects of APOEɛ4 genotype on age-associated change in cognitive functions among Japanese middle-aged and older adults: A 20-year follow-up study

Background and aimsCarriers of the apolipoprotein E ε4 allele (APOEɛ4) have an increased risk of developing dementia (e.g., Alzheimer's disease). However, it is less clear whether the APOEɛ4 might also be involved in cognitive aging among the non-clinical population of older adults. While some studies have suggested that the APOEɛ4 is related to accelerated cognitive decline in the normal aging process, others have failed to provide compelling evidence of such an impact. Notably, these discrepancies may depend on methodological shortcomings, including short time spans, few assessments, and small sample sizes. The present study overcomes the above limitations and aims to clarify the impact of the APOEɛ4 genotype on long-term longitudinal changes in cognitive functions in middle-aged and older adults in Japan. Methods and resultsThe data were retrieved from the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) survey (N = 1832; 40 to 79 years of age at baseline). The participants were tested over nine waves covering a period of approximately 20 years. Latent Growth Curve (LGC) modeling was employed to test the impact of the interaction between APOEɛ4 status and age on several cognitive functions. Four tests of the WAIS-R were administered: Information, Similarities, Picture completion, and Digit Symbol Substitution Test (DSST). The results showed that the APOEɛ4 carriers experienced a more pronounced decline in the DSST (p = 0.001) and Similarities (p = 0.022) tests. A similar tendency was found in the Information test (p = 0.034). By contrast, no effect was found in the Picture completion test (p = 0.563). ConclusionsAPOEɛ4 carriers seem to exhibit a steeper cognitive decline, which becomes apparent in old age. This effect is more robust in fluid cognitive skills (DSST) than crystallized cognitive skills (Information and Similarities). Overall, the APOEɛ4 genotype may be a significant risk factor in normal (i.e., non-clinical) cognitive aging.

<I>In vivo</I> vascular mapping of the human hippocampus using MICRO imaging

BACKGROUND: There is an urgent need for better detection and understanding of vascular abnormalities at the micro-level, where critical vascular nourishment and cellular metabolic changes occur. This is especially the case for structures such as the midbrain and hippocampus, where both the feeding and draining vessels are quite small. The hippocampus is a complex grey matter structure that plays an important role in spatial and episodic memory. It can be affected by a wide range of pathologies including vascular abnormalities. Being able to monitor vascular changes in normal aging in various hippocampal subfields will allow us to better understand vascular vulnerability across the hippocampus.
 METHODS: We recently introduced the concept of microvascular in-vivo contrast revealed origins (MICRO) protocol to image micro-cerebral vessels.1-3 MICRO uses ferumoxytol, an ultra-small superparamagnetic iron oxides (USPIO) agent, to induce susceptibility in the arteries and veins; and by imaging with high resolution (0.22×0.44×1 mm3) susceptibility weighted imaging sequence (SWI) at 3 T. Although the increased vascular susceptibility enhances the visibility of small sub-voxel vessels, the accompanying strong signal loss of the large vessels deteriorates the local tissue contrast. Hence, data are collected at different time points during a gradual administration (final concentration = 4 mg/kg) of ferumoxytol. Dynamically acquired SWI data were co-registered and combined (phase gradient-based adaptive combination or SWIPGAC) to reduce the blooming artifacts from large vessels, preserving the small-vessel contrast.
 RESULTS: The presence of ferumoxytol helped to enhance the microvasculature, something that has previously only been demonstrated in cadaver brain studies. Figure 1 shows the difference between the pre-contrast SWI and SWIPGAC data in visualizing the micro-vasculature across four healthy subjects. The intra-hippocampal and superficial major arteries (obtained through a non-linear subtraction method) and veins (obtained by averaging the T1-shortening map, pre-contrast quantitative susceptibility mapping (QSM) and pre-contrast R2* maps) are used as an overlay in the third column to better visualize the major vessels penetrating and draining the hippocampus. The hippocampal fissure, along with the fimbria, granular cell layer of the dentate gyrus and cornu ammonis layers (except for CA1), showed higher micro-vascular density than the other parts of hippocampus. The CA1 region exhibited a significant correlation with age (R=−0.37, p<0.05, n=37). demonstrating an overall loss of hippocampal vascularity in the normal aging process. Moreover, the vascular density reduction was more prominent than the age correlation with the volume reduction (R=−0.1, p>0.05, n=37) of the CA1 subfield.
 CONCLUSIONS: With this USPIO-induced increase in susceptibility comes the potential to study the cerebral micro-vasculature using high-resolution SWI. There was a strong negative correlation between hippocampal functional vessel density (FVD) (especially in CA1) and age. This FVD reduction was more prominent than volume reduction vs age, suggesting that vascular atrophy may precede reductions in tissue volume. Mapping the hippocampal vasculature has immediate implications for understanding the effects of normal aging and the etiology of many neurovascular diseases. MICRO imaging brings us into the decade of imaging the microvasculature of the entire human body.

Sarcopenia: An Age-Related Multifactorial Disorder.

Sarcopenia is a disease characterized by a gradual decline in skeletal muscle mass and strength that accompanies the normal aging process. The disease is associated with various adverse health outcomes in the geriatric population, such as prolonged hospital admission, disability, poor quality of life, frailty, and mortality. Factors involved in the development of age-related sarcopenia include anorexia, hormone level alterations, decreased neural innervation, low muscular blood flow, cytokine dysregulation, altered mitochondrial activity, genomic instability, intracellular proteolysis, and insulin resistance. Understanding the underlying mechanisms may facilitate the development of efficient prophylactic and therapeutic strategies to improve the quality of life in elderly individuals. Thus, the present review highlights literature regarding the mechanism of sarcopenia development in elderly patients.