Anti-Aging Effects of Terminalia bellirica, Phyllanthus emblica, Triphala, and Carica papaya Extracts for Sustainable Youth

As the human lifespan becomes longer, many people invest time and money in managing external beauty. However, managing external beauty has the disadvantage of causing side effects or that the effect does not last. Therefore, research and development are required to maximize effectiveness, eco-friendliness, and sustainably in beauty management. The purpose of this study was to experimentally identify the anti-aging effects, such as skin wrinkle and elasticity improvement, of extracts from Bahera, Phyllanthus emblica, Triphala, and Carica papaya, and to confirm their development as whitening and wrinkle functional cosmetic materials. In this study, a solid mixture was prepared using eco-friendly Terminalia bellirica, amla (Phyllanthus emblica), Triphala, and Carica papaya, and experimental samples were extracted. Antioxidant tests, antibacterial activity tests, polyphenol and flavonoid content, and deodorization tests were conducted to test the efficacy of experimental samples. The procedures and methods of these experiments are summarized in the following article. In this study, we found that the Bahera, Phyllanthus emblica, Triphala, and Carica papaya extracts had significant effects on whitening and wrinkle improvement, and that the effects of using ethanol-based extracts as the co-solvent were even greater. In other words, extracts of Bahera, Phyllanthus emblica, Triphala and Carica papaya showed antioxidant, whitening, and anti-wrinkle effects, and extracts that used ethanol as a co-solvent showed greater effects. In particular, we found that the optimal concentration of ethanol as a co-solvent maximizes its effectiveness at 70%.

Identification of Somatic Mutations From Bulk and Single-Cell Sequencing Data

Somatic mutations are DNA variants that occur after the fertilization of zygotes and accumulate during the developmental and aging processes in the human lifespan. Somatic mutations have long been known to cause cancer, and more recently have been implicated in a variety of non-cancer diseases. The patterns of somatic mutations, or mutational signatures, also shed light on the underlying mechanisms of the mutational process. Advances in next-generation sequencing over the decades have enabled genome-wide profiling of DNA variants in a high-throughput manner; however, unlike germline mutations, somatic mutations are carried only by a subset of the cell population. Thus, sensitive bioinformatic methods are required to distinguish mutant alleles from sequencing and base calling errors in bulk tissue samples. An alternative way to study somatic mutations, especially those present in an extremely small number of cells or even in a single cell, is to sequence single-cell genomes after whole-genome amplification (WGA); however, it is critical and technically challenging to exclude numerous technical artifacts arising during error-prone and uneven genome amplification in current WGA methods. To address these challenges, multiple bioinformatic tools have been developed. In this review, we summarize the latest progress in methods for identification of somatic mutations and the challenges that remain to be addressed in the future.

Thyroid disorders and development of cognitive impairment: a review study

Dementia is a neurological disorder that is spreading with increasing human lifespan. In this neurological disorder, memory and cognition are declined and eventually impaired. Various factors can be considered as the background of this disorder, one of which is endocrine disorders. Thyroid hormones are involved in various physiological processes in the body; one of the most important of them is neuromodulation. Thyroid disorders, including hyperthyroidism or hypothyroidism, can affect the nervous system and play a role in the development of dementia. Despite decades of investigation, the nature of the association between thyroid disorders and cognition remains a mystery. Given the enhancing global burden of dementia, the principal purpose of this study was to elucidate the association between thyroid disturbances as a potentially modifiable risk factor of cognitive dysfunction. In this review study, we have tried to collect almost all of the reported mechanisms demonstrating the role of hypothyroidism and hyperthyroidism in the pathogenesis of dementia.

The origins and functional effects of postzygotic mutations throughout the human lifespan

Postzygotic mutations (PZMs) begin to accrue in the human genome immediately after fertilization, but how and when PZMs affect development and lifetime health remains unclear. To study the origins and functional consequences of PZMs, we generated a multi-tissue atlas of PZMs from 948 donors using the final major release of the Genotype-Tissue Expression (GTEx) project. Nearly half the variation in mutation burden among tissue samples can be explained by measured technical and biological effects, while 9% can be attributed to donor-specific effects. Through phylogenetic reconstruction of PZMs, we find that their type and predicted functional impact varies during prenatal development, across tissues, and the germ cell lifecycle. Remarkably, a class of prenatal mutations was predicted to be more deleterious than any other category of genetic variation investigated and under positive selection as strong as somatic mutations in cancers. In total, the data indicate that PZMs can contribute to phenotypic variation throughout the human lifespan, and, to better understand the relationship between genotype and phenotype, we must broaden the long-held assumption of one genome per individual to multiple, dynamic genomes per individual.

The genomics of exceptional longevity in rockfishes refine genetic foundations of human lifespan variation

Longevity is a defining, heritable trait that varies dramatically between species. To resolve the genetic regulation of this trait, we have mined genomic variation in rockfishes, ranging in longevity from 11 to over 205 years. Shifts in rockfish longevity occurred multiple times independently, and in a short evolutionary time frame, thus empowering convergence analyses. Our analyses reveal a common network of genes under convergent restricted evolution in long-lived lineages, encompassing established aging regulators such as insulin-signaling, yet also identify flavonoid (aryl-hydrocarbon) metabolism as a novel pathway modulating longevity. Further, these genes were used to refine human longevity GWAS, identifying the aryl-hydrocarbon metabolism pathway to be significantly associated with the 99th percentile of human longevity, independently validating its importance and conservation. This evolutionary intersection highlights a novel, conserved genetic architecture that associates with the evolution of longevity across vertebrates and provides actionable targets for research into lifespan and healthspan modulation.

The Interplay Between Stress Related Genes and Its Role in Human Longevity: Insights for Translational Studies

Human lifespan is a multifactorial trait resulted from complicated interplay among many genetic and environmental factors. Despite substantial progress in clarifying many aspects of lifespan’ variability the mechanism of its multifactorial regulation remains unclear. In this paper we investigate the role of genes from integrated stress response (ISR) pathway in such regulation. Experimental studies showed that persistent cellular stress may result in cellular senescence (for proliferating cells), or in apoptosis (for post-mitotic cells) which may affect health and lifespan in laboratory animals. These studies also showed which ISR genes are likely to interplay to produce joint effects on these traits. Note that in humans, the interplay between these genes does not necessarily influence these traits. This is because biological mechanisms regulating these traits in laboratory animals and humans may differ. This means that, when possible, the experimentally detected connections promising for human applications, should be verified using available human data before their testing in expensive clinical trials. In this paper we used HRS data to test connection between SNPs from the EIF2AK4 gene that senses cellular stress signals and the DDIT3 gene from the apoptosis regulation part of the ISR. We found genome wide significant associations between interacting SNPs from these genes and longevity. This result shows that available human data may be successfully used for making important steps in translation of experimental research findings towards their application in humans. Following this strategy may increase efficiency of clinical trials aiming to find appropriate medications to promote human health and longevity.

Experiencing a Natural Disaster Accelerates Aging of the Immune System

Extreme adverse events such as natural disasters can accelerate disease progression and promote chronic inflammation. These phenotypes also increase in prevalence with age, suggesting that experiencing adversity might accelerate aging of the immune system. Adversity can induce persistent gene regulatory changes which may mechanistically explain the immune similarities between aging and adversity. To test how immune system aging is accelerated following a natural disaster, we measured the impact of Hurricane Maria on peripheral blood immune cell gene expression in a population of free-ranging rhesus macaques (Macaca mulatta) from before (n=435) versus after (n=108) Hurricane Maria. Experiencing Hurricane Maria altered the expression of 260 genes (FDR<10%), which were primarily involved in the inflammatory response. There was significant overlap in these hurricane-affected and age-associated genes with 40% (n=104) being associated with both the hurricane and aging, more than double the expected amount (Fisher’s Exact Test OR=3.7, p=4.06 x 10–21). The effects of the hurricane and aging on gene expression were also significantly correlated (rho=0.23, p=1.33 x 10-84), suggesting that they alter similar molecular pathways in the immune system. Further, we found that animals that experienced the hurricane had a gene expression profile that was, on average, 1.6 years older than animals that did not experience the hurricane (the equivalent of 6–7 years in a human lifespan, p=0.003). Together, our results provide some of the first evidence that extreme natural disasters mechanistically accelerates aging in the immune system.

Toward Age-Friendly High Education: An Intergenerational Participatory Co-Design Approach

Objective When aging becomes a global challenging, we believe it is timely important to equip aging knowledge among university students regardless of their disciplinary study subjects. This study aims to describe principles and process of development an aging-related curriculum in high education entitled “Intergenerational Participatory Co-design Project (IPCP)” and evaluate its impacts. Methodology: Guided by a key principle of involving participants of any learning context as co-creators of both the learning process and learning outcomes, IPCP went through four stages of development including capacity building, co-creation on learning objectives, deliberated content learning, and learning outcome dissemination. Mixed methodology including qualitative in-depth interview and quantitative questionnaire were applied in evaluation. A total of 26 participants, from three generations recruited from one university, one secondary school, and a pool of senior champions under a geron-infusion initiative participated. Findings: after attaining capacity building workshops applying Optimal Quality Intergeneration Interaction Framework, three learning groups formulated. A common theme “preserving cultural heritage” emerged, while each group has identified a specified focus (e.g., food, Tai Ji, and historic sites guide). Quotes collected and survey data revealed positive impacts in reducing stereotype and enhancing learning experiences. Conclusion IPCP demonstrated good practices in role models in multi-disciplinary collaboration in pedagogy innovation. It also paved solid way towards a learning community interwoven with continuous innovation: IPCP becomes a pioneer contributor of library’s digital data hub solution; common core office starts to develop a human lifespan cluster; two research team members started new collaboration on geron-infusion in Faculty of Education.

Exploring the effects of birth order on human lifespan in Polish historical populations, 1738–1968

While the relationships between birth order and later outcomes in life, including health and wealth, have been the subject of investigation for several decades, little or no data exist regarding the relationship between birth order and life expectancy in the Polish population. The aim of this study was to explore the link between birth order and lifespan in Polish historical populations. We obtained 8523 records from a historical dataset that was established for parishioners from the borough of Bejsce, including 4463 males and 4060 females. These data pertain to the populations that lived over a long period in a group of localities for which parish registers were well preserved. The Mann-Whitney U test, the Kruskal-Wallis ANOVA and ANCOVA were run. The results strongly suggest that birth order affects male longevity. However, no such association was found for females. On balance, the hypothesis that first-born boys live longer because they are born to relatively younger parents has received some empirical support and deserves further study. We hypothesise that the effects of birth order on human health and lifespan might be overshadowed by other factors, including educational attainment, socioeconomic status and lifestyle.

Kuakini HHP Center for Translational Research on Aging: Aims and Preliminary Findings

Kuakini Medical Center (Kuakini) is creating an interdisciplinary Hawai’i-based Center for translational research on aging. This Center will build upon Kuakini’s five-decades of NIH-funded research, its 420,000-specimen biorepository, and existing strengths in aging research, notably, the 56-year ongoing Kuakini Honolulu Heart Program cohort study (Kuakini HHP), Kuakini Honolulu-Asia Aging Study (Kuakini HAAS), and Kuakini HHP Offspring Study. The overall goal is to find practical means to enhance healthy human lifespan (healthspan). Four research project leaders (RPLs) have been selected from various disciplines for mentorship in translational aging research. The first RPL presentation will introduce a novel mouse model, enabling controlled expression of the pro-longevity gene FoxO3, and assess the impact on lifespan and healthspan phenotypes in mice. These phenotypes will be compared to similar phenotypes in humans with/without the FOXO3 longevity genotype. The second RPL presentation will assess the relation between leukocyte telomere attrition rates (from banked blood collected at three time points over 20-plus years) in older Kuakini HHP men with/without the FOXO3 longevity genotype. The third RPL presentation will assess whether FOXO3 genotype, peripheral leukocyte telomere dynamics (attrition rate, telomerase activity) and inflammatory cytokines mediate the human brain integrity and function with age. This project will utilize structural and functional MRI data from male and female Kuakini HHP Offspring Study participants. The fourth RPL presentation will assess whether APOE e2, e4, and FOXO3 longevity-associated alleles impact 34-year incidence of intracerebral hemorrhage. We will summarize the findings, address the healthspan implications and provide future directions. Supported by NIH 5P20GM125526.