Current Aging Science - Volume 13, Issue 2, 2020

Aging has been considered a progressive decrease of a living organism’s homeodynamics, which indicates a reduction of psycho-biological resilience. This narrative review provides an overview of the available literature related to the holistic approach of integrative medicine, Psychoneuroendocrineimmunology (PNEI) and hormesis in the aging process. On the basis of Pathophysiology of cell senescence and of chronic degenerative diseases, possible preventive/therapeutic pathways have been examined. Chronic low grade cellular inflammation and chronic stress have been shown as the general interlinked factors inducing aging, on the basis of complex biochemical, cell and multi-organ derangements. The main cell degenerative processes which have been related to aging are: altered mitochondria DNA/metabolism, excessive oxidative stress, glycation, alteration of autophagy and proteasome, and genome alterations. Literature about longevity-targeting interventions, beyond conventional medicine, describes a spectrum of possible measures to improve psycho-biological resilience, based on the PNEI paradigm, on hormesis and upon mitochondriatargeted interventions. Calorie restriction, exercising, fasting, nutraceuticals, sleep regulation, specific breathing, meditation and psychotherapy are discussed, among others.

Melatonin is well known as a neuroendocrine hormone that promotes sleep. However, the many other attributes of melatonin are less apparent and not as widely appreciated. The purpose of this review is to summarize the qualities of melatonin relating to immune function. The relevance of melatonin in partially or wholly restoring optimal function, in a series of disorders related to immune dysfunction, is addressed in this report. This includes the potential relief of both autoimmune diseases and many other ailments involving abnormal immune responses, including the overall diminished effectiveness of body defenses occurring with aging. Disease states affecting a wide range of organ systems have been reported as benefitting from melatonin administration and are discussed here. A separate section addresses the potential role of melatonin in the mitigation of age-related neurological diseases, in view of the increasing importance of this area. The likely mechanistic basis of the properties by which melatonin may confer protection by its acting on immune function is also described.

In developed countries, people of advanced age go permanently blind most often due to age-related macular degeneration, while at the global level, this disease is the third major cause of blindness, after cataract and glaucoma, according to the World Health Organisation. The number of individuals believed to suffer from the disease throughout the world has been approximated at 50 million. Age-related macular degeneration is classified as non-neovascular (dry, non-exudative) and neovascular (wet, exudative). The exudative form is less common than the non-exudative as it accounts for approximately 10 percent of the cases of the disease. However, it can be much more aggressive and could result in a rapid and severe loss of central vision. Similarly, with age-related macular degeneration, Alzheimer’s disease is a late-onset, neurodegenerative disease affecting millions of people worldwide. Both of them are associated with age and share several features, including the presence of abnormal extracellular deposits associated with neuronal degeneration, drusen, and plaques, respectively. The present review article highlights the pathogenesis, clinical features, and imaging modalities used for the diagnosis of neovascular age-related macular degeneration. A thorough overview of the effectiveness of anti-VEGF agents as well as of other treatment modalities that have either lost favour or, are rarely used, is provided in detail. Additionally, the common histologic, immunologic, and pathogenetic features of Alzheimer’s disease and age-related macular degeneration are discussed in depth.

Background: Verbal Fluency (VF) tasks are known as multimodal measures clinically useful for monitoring cognitive decline during the aging process. Considering that the executive control observed along VF tasks calls for a set of functions directing the behavior toward a general goal, it may be assumed that there is a correspondence between VF ability and Functional Capacity (FC). Methods: With this assumption in mind, the author aimed at performing a literature research on VF ability and FC within aging. Results: Only four studies whose title/abstract presented the target key-terms, partially fulfilled the adopted criteria and were selected for discussion. Taken together, these articles attempted to correlate cognitive material to aspects of functionality, one of which not doing so directly with the elderly and another with no specific association with VF abilities. Conclusion: Theories suggest that VF might be associated with complex executive mechanisms. Still, a theoretical scheme and controlled researches possibly able to shed light on the underlying balance among the VF abilities and functionality within aging are as yet, unknown.

Aim: The study of the impact of socio-economic, demographic factors and polymorbidity on the quality of life associated with health (HRQoL) in elderly people from Japan and Russia. Background: Factors affecting the quality of life of the elderly in both countries are poorly understood. Objective: Make a comparative analysis of factors affecting the quality of life of the elderly of both sexes in Japan and Russia. Methods: The age range in this study is 65-95 years old. For the study of HRQoL, a questionnaire Health Status Survey-Short Form 36v2 was used, including two main domains: physical and mental health. The level of polymorbidity was studied using CIRS-G. The linear regression model of the influence of variables upon HRQoL was calculated for SES, demographic characteristics, and morbidity. Result: Strong associations with HRQoL in the combined sample had a living together with relatives (r=6.94 (5.17-8.72) p<0,05), the incidence rate (r=8.50 (5.51-11.49), p<0.01) and the older age (r=5.39 (2.63-8.16), p<0,01.). The elderly inhabitants of Japan had a higher self-assessment for physical health in the age ranges 65-74 and over 85 years old (p<0.05), and a higher selfassessment of mental health at the age of 75-84 years old. Sixty-eight elderly Japanese and 48% Russians estimated their physical health as normal. Conclusion: The effect of living together, morbidity and age upon HRQoL is manifested equally strongly both among the inhabitants of Japan and among the Russians. The elderly Japanese estimate the state of physical and mental health as a whole higher than their Russian peers.

Background: The average lifespan and the aging population are rising worldwide. So Neurodegenerative Disease (ND) will be one of the most common challenges associated with this population and would be more prevalent in future. The use of Acetylcholinesterase (AChE) inhibitors is one of the most important strategies for memory impairment. Medicinal plants are the most known natural source for accessing the new therapeutic agents. Objective: In this work, we aimed to study in vitro anticholinesterase effect of different concentrations (10, 100, 250, 500, 750 and 1000 μg/ml) of total extract of N. sativa (NTE) and its separated fractions and to study the kinetic of AChE enzyme in the presence of two concentrations of NTE (10 and 100 μg/ml). Methods: Maceration method was used for NTE preparation and different fractions of Petroleum Ether (PTE), Chloroform (CHF) and Methanol (MF). NTE, fractions and the main component of the plant, Thymoquinone (TQ), were assayed for AChE inhibition, using Ellman’s method. Kinetic study of the AChE enzyme was studied in the presence of NTE at 10 and 100 μg/ml using Linweaver- Burk plot too. Results: NTE and all the separated fractions inhibited AChE enzyme in a concentration-dependent manner. The greatest inhibition was shown by CHF and PEF fractions (86.97% and 79.99% at 1000 μg/ml, respectively). With less intensity, NTE, TQ and MF exhibited 76.32%, 68.98 % and 48.39% enzyme inhibition at 1000μg/ml, respectively. The least IC50 value was due to CHF fraction in AChE inhibition (98.28 ± 6.74 μg/ml). Kinetic profile exhibited the mixed mode of AChE inhibition by NTE. This indicates that a particular substance could not be responsible for AChE inhibition, and probably a collection of phytochemicals are involved in this process. Conclusions: N. sativa is a good candidate for seeking the new anticholinesterase agent and could be considered as a good supplement for the health of the elderly.

Background: Solving the nervous system requires understanding how it generates inner sensations of "mind" within it. It was possible to derive a hypothesis of brain functions where the formation of a spectrum inter-postsynaptic (inter-spine) functional LINKs (IPLs) are the key structural changes responsible for encoding at the time of learning and are used for inducing the inner sensation of memory, both taking place at millisecond timescales. Since stages of ontogeny reflect possible stages of evolution, it is possible to examine whether IPLs have features of an evolved mechanism. Objective: To examine whether 1) IPLs have features of an evolved mechanism, 2) significant neuronal death during ontogeny leads to evolutionary adaptations for preventing cell death among the surviving neurons, and 3) loss of these adaptations lead to cellular changes that can cause agingrelated neurodegeneration. Methods: Key milestone changes of the ontogeny of the nervous system were examined to test whether they match with a feasible sequence of steps that lead to the formation of IPLs. Results: Several developmental stages can explain a probable sequence of events that lead to IPL formation among synaptically-connected neurons. When internal sensations generated by the IPLs started providing survival advantage, evolution has started preserving the IPL circuitry. A stage of inter-spine fusion possibly leads to a) significant neuronal death during the early stages of development, and b) trigger an adaptation in the surviving cells to stabilize and prevent the IPLs from undergoing fusion. Since there are no irreversible steps for maintaining the stability of IPLs, agingrelated factors may destroy the adaptation mechanism and destabilize the IPLs predisposing them to cause neurodegeneration. Conclusion: The derived testable IPL mechanism that can explain nervous system functions is capable to have evolved. An adaptation to prevent IPL hemifusion from progressing to fusion is likely the last stage of nervous system evolution. Since the IPL mechanism is utilized during every event of learning, any aging-related factors that can weaken this adaptation can cause IPL fusion and lead to neurodegeneration.

Objectives: Although Dual-energy X-ray Absorptiometry (DXA) is gold standard for osteoporosis diagnosis, several reports have shown discordant T-score values measured by Quantitative Computed Tomography (QCT) and DXA especially in obese subjects, but it is still not clear whether BMD measurement by two modalities is affected by overall obesity or central obesity in postmenopausal females. Therefore, the aims of this study were to compare BMD and T-scores by DXA and QCT and to evaluate whether these two osteoporosis assessment modalities yield different T-score values in postmenopausal females with obesity and central obesity. Methods: This cross-sectional study enrolled 44 postmenopausal females, referred for osteoporosis screening. Anthropometric indices (BMI-body mass index, WC-waist circumference and ICOindex of central obesity) were measured and females underwent an assessment of bone mineral density by DXA and QCT. Results: Lumbar Spine (LS) T-score values were observed to be significantly lower by DXA compared to qCT in females with BMI >25 kg/m2, (-1.9±1.5 vs. -2.3±1.2; p=0.039), in females with WC>88 cm(-1.9±1.5 vs. -2.4±1.2; p=0.008) and in females with ICO>0.5(-1.96±1.4 vs. -2.5±1.2; p=0.004). However, in normal-weight females and in those without central obesity, LS T-scores by DXA were not different than qCT. DXA at lumbar spine and proximal femur revealed osteoporosis in 47.7% and 11.4% respectively, while QCT detected osteoporosis in 61.4% of females (p<0.001). Measures of central obesity; ICO and WC were not associated with QCT bone mineral density (BMD) (r=0.14 and r=0.21, respectively), but were positively associated with both DXALS BMD (r=0.29 and r=0.31; p<0.05) and DXA proximal femur BMD (r=0.41 and r=0.44; p<0.01). Conclusion: Our results suggest that obesity is associated with lower T-scores by DXA compared to QCT. Caution is needed when assessing osteoporosis status in obese postmenopausal females. However, further studies with larger sample size are needed to confirm the findings.

Background: Alzheimer's Disease (AD) is a multifactorial disease affected by various factors including genetics. Although APOE is considered the major and strongest genetic risk factor, other genetic factors such as rs3851179G>A in PICALM have been reported despite that not being fully clear. Objective: We first aimed to investigate the correlation between rs3851179G>A in PICALM and AD in Lebanese individuals affected with AD. Then, we further investigated its overall effect in five different populations from the Mediterranean region (Turkey, Italy, Spain, France and ours) through performing a meta-analysis. Methods: We investigated the relationship between the rs3851179G>A and AD in 109 Lebanese individuals (54% affected with AD) using allele-specific PCR. Sanger Sequencing was also used to verify genotyping. Results: Using a multiple logistic regression model adjusted for many covariates, only rs3851179G>A showed a negative correlation with AD (OR=0.28, P=0.04 and OR=0.07, P=0.01 for GA and AA, respectively). To go further, a meta-analysis was conducted using studies on 3,619 participants from five different populations that belong to countries surrounding the Mediterranean (Turkey, Italy, Spain, France and ours). The sensitivity test showed no genetic heterogeneity for rs3851179G>A in the pooled analysis (P=0.44 and I2=0%) and in each individual study (P>0.05). Using an additive model, our results showed a significant association between rs3851179G>A and AD (OR=0.91, P=0.003). The funnel plot was a symmetrical inverted funnel and no significant publication bias was found for our model (P=0.46). Conclusion: The rs3851179A allele in PICALM tends to have a protective factor against AD in the Mediterranean region.

Background: Aging is associated neuroendocrine changes in women. Animals can be used to model these changes, as well as changes in reproductive behavior. Objective: The current study was designed to characterize mating behavior across age and assess the effects of age and sexual history on mating behavior. Methods: Sexual motivation was assessed using the partner-preference test, in which a female rat is given the choice to interact with a same-sex conspecific or a sexually-vigorous male rat, with which she can mate. Results: Across repeated mating tests (2-12 months of age), female rats spent more time with the male, displayed more solicitation behaviors, were less likely to leave the male after mounts, but visited both stimulus animals less frequently. Comparing a separate group of age-matched, hormoneyoked female rats mated for the first time at 12 months of age to female rats mated for the first time at 2 months of age showed that the 12 month rats visited both stimulus animals less, were less likely to leave the male after mounts, took longer to return to the male after mounts, and displayed fewer solicitation behaviors than their younger counterparts. Relative to middle-aged female rats once they were sexually experienced, 12 month naïve rats spent less time with the male, were more likely to leave the male after mounts, and displayed fewer solicitation behaviors. Furthermore, 12 month naïve rats failed to discriminate between the stimulus animals, visiting both stimulus animals at the same rate unlike 2 month naïve or 12 month experienced rats. Conclusion: Taken together, these results suggest that aging affects some measures of sexual behavior, but most effects of age can be mitigated by regular, repeated mating.

Background: Aging is an organized biological process that is regulated by highly interconnected pathways between different cells and tissues in the living organism. Identification of similar genes between tissues in different ages may also help to discover the general mechanism of aging or to discover more effective therapeutic decisions. Objective: According to the wide application of model-based clustering techniques, the aim is to evaluate the performance of the Mixture of Multivariate Normal Distributions (MMNDs) as a valid method for clustering time series gene expression data with the Mixture of Matrix-Variate Normal Distributions (MMVNDs). Methods: In this study, the expression of aging data from NCBI’s Gene Expression Omnibus was elaborated to utilize proper data. A set of common genes which were differentially expressed between different tissues were selected and then clustered together through two methods. Finally, the biological significance of clusters was evaluated, using their ability to find genes in the cell using Enricher. Results: The MMVNDs is more efficient to find co-express genes. Six clusters of genes were observed using the MMVNDs. According to the functional analysis, most genes in clusters 1-6 are related to the B-cell receptors and IgG immunoglobulin complex, proliferating cell nuclear antigen complex, the metabolic pathways of iron, fat, and body mass control, the defense against bacteria, the cancer development incidence, and the chronic kidney failure, respectively. Conclusion: Results showed that most biological changes of aging between tissues are related to the specific components of immune cells. Also, the application of MMVNDs can increase the ability to find similar genes.