Growing Life Expectancy Research Articles

How many people will live and die with serious illness in Ireland to 2040? Estimated needs and costs using microsimulation

As populations age, more people worldwide will live and die with serious illness like cancer, heart disease and dementia. Prior projections of serious illness prevalence and end-of-life care needs have typically used static population-level methods. We estimated future disease prevalence and healthcare costs by applying dynamic microsimulation models to high-quality individual-level panel data on older adults (aged 50 + ) in Ireland. We estimated that the number of people living and dying with serious illness will increase approximately 70 % over 20 years. Per-capita annual costs both at end of life and not at end of life increase substantially due to ageing populations and growing complexity. Total health system expenditures on care for people with serious illness are projected to double before accounting for rising cost of inputs in real terms. Decomposition of these estimates suggests that 39 % of additional costs are accounted for by rising absolute numbers of older people, 37 % by changing age distribution and growing life expectancy, and 23 % due to rising individual complexity including morbidity and functional limitations. Our results and methods will be of interest to other countries planning for the future population health needs, and formidable health system resources associated with these needs, in the coming years.

Intralesional administration of L19IL2/L19TNF in high-risk locally advanced basal cell carcinoma or cutaneous squamous cell carcinoma.

TPS9617 Background: Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) account for 99% of skin neoplasms, with a rising incidence due to increased sun exposure and growing life expectancy. Approximately 0.8-5% of patients (pts) develop high-risk locally advanced (LA) disease, which is treated with surgery, radiotherapy, sonic hedgehog inhibitors, PD1-based immune checkpoint blockade, or chemotherapy. While surgery offers high cure rates, factors such as location, functional and cosmetic impairment, or patient factors including age, comorbidities, and personal preferences may preclude surgery. Intralesional treatment with immunostimulatory drugs represents an attractive therapeutic approach to treat LA BCC and LA cSCC. Here, we investigate a combination of two immunocytokines (Bifikafusp alfa (L19IL2) and Onfekafusp alfa (L19TNF)) targeting the extradomain B of fibronectin (EDB) for the treatment of high-risk locally advanced BCC and cSCC. EDB is an oncofetal antigen that is undetectable in virtually all healthy adult tissues but becomes highly expressed in tumors, including BCC and cSCC. Methods: In a single-arm phase II study (NCT04362722), pts with locally advanced, non-metastatic, node-negative, single, or multifocal BCC or cSCC not eligible for surgery or radiotherapy are treated with four weekly intratumoral administrations of L19IL2/L19TNF. The study is divided into two parts: a first exploratory part with a total of 40 pts with laBCC or lacSCC, and a second part where the laBCC cohort has been expanded to up to 72 pts not eligible for surgery or radiotherapy. The first part of the trial has been completed with 28 laBCC pts and 12 lacSCC pts evaluable for safety and efficacy. The pre-specified activity goal for the first stage of accrual was met, and the second stage of accrual began in September 2023, with a total of 39 BCC and 18 cSCC pts enrolled so far. Clinical trial information: NCT04362722 .

Prawnokarne ujęcie eutanazji w Austrii – uwagi do orzeczenia austriackiego Trybunału Konstytucyjnego z 11.12.2020 r., G 139/2019

International organisations consistently refuse to take a stand on worldview issues, leaving relevant rulemaking to domestic legislatures. Therefore, it is the state’s privilege and responsibility at the same time to develop legal regulations in this field. Progress in medicine and steadily growing life expectancy have caused the issues of in vitro fertilisation, abortion and euthanasia to be of more import. On 11 December 2020, the Austrian Constitutional Court issued a judgment (in G 139/2019) which may be deemed groundbreaking for the admissibility of euthanasia in Austria. This ruling may also be significant for legal systems in other count ries. Therefore, this paper takes as its subject-matter the aforementioned judgment of the Austrian Constitutional Court. The objective was to analyse it and its legal effects. The research question was formulated as follows: what changes will the judgment of the Austrian Constitutional Court of 11 December 2020 in G 139/2019 bring in Austria’s criminal legal reaction to euthanasia? The article describes the provisions applicable in Austria which penalise crimes against life, presents the historical background of assisted suicide in Austrian law, analyses the ruling of the Austrian Constitutional Court, and draws final conclusions. The most important conclusions arising from the research are that one must continuously review whether the provisions of criminal law concerning crimes against life are adequate to the current reality and that the potential admissibility of euthanasia inextricably involves further changes to the law – the lawmakers would have to specify its legal conditions and regulate the procedure itself.

Correlation between the Cognitive Status (SIRT1) and the Metabolic Function in Geriatric Patients Using the Indonesian Version of the Montreal Cognitive Assessment (MoCA-INA).

A growing life expectancy may result in a chronic medical condition and multimorbidity because the aging process leads to a decrease in cognitive and physiological function. These risks may affect the quality of life of geriatrics. The present study aims to determine the correlation between cognitive status (in terms of SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent class III deacetylase) and metabolic function (in terms of the lipid profile, kidney function, and blood glucose) in geriatric patients. The differences in the parameters of metabolic function in the participants' cognitive status were determined by using the Indonesian version of the Montreal Cognitive Assessments (MoCA-Ina). The elderly participants (n = 120) were recruited at three sites in Indonesia from March to October 2022. Our study demonstrated a negative correlation between the cognitive status of geriatric patients and their metabolic function, represented by the MoCA-Ina score with a linear regression equation of y = 0.27 - 2.4 ×10-3x. Higher levels of LDL-C, cystatin C, and HbA1c were found in the Severe-Moderate Cognitive Impairment group. Determining the SIRT1 levels may be beneficial in predicting both the cognitive and metabolic status of geriatrics because this protein is among numerous metabolic sensors in the hypothalamus.

Healthy ageing trends in England between 2002 to 2018: Improving but slowing and unequal

Growing life expectancy and a rising proportion of older people make the issue of whether cohorts are ageing better a key individual, social and economic issue. Using data from the English Longitudinal Study of Ageing we characterise how frailty develops with age, how this differs across demographic groups, whether more recent cohorts are ageing better and what the key areas of focus for health policy should be. We find cohort effects such that frailty at each age has been decreasing over time but that this trend shows modest signs of slowing and is less pronounced for those with lower wealth. Improvements across cohorts reflect improvements in ADLs, cognitive function, and mobility but limited progress in reducing the incidence of diseases such as cancer, cardiovascular disease, etc. We find mobility and ADLs the main driver of average differences across regions but cross-regional differences are driven more by within than between group inequality.

Halting aberrant DNA methylation via in silico Identification of potent inhibitors of DNMT3B enzyme: Atomistic insights

To date, Cancer remains a global threat due to its impact on growing life expectancy. With the many efforts and methods of combating the disease, complete success remains a challenge owing to several limitations including cancer cells developing resistance through mutations, off-target effect of some cancer drugs resulting in toxicities, among many others. Aberrant DNA methylation is understood to be the primary reason for improper gene silence, which can result in neoplastic transformation, carcinogenesis, and tumour progression. DNA methyltransferase B (DNMT3B) enzyme is considered a potential target for the treatment of several cancers due to its important role in DNA methylation. However, only a few DNMT3B inhibitors have been reported to date. Herein, in silico molecular recognition techniques such as Molecular docking, Pharmacophore-based virtual screen and MD simulation were employed to identify potential inhibitors of DNMT3B that can halt aberrancy in DNA methylation. Findings initially identified 878 hit compounds based on a designed pharmacophore model from the reference compound Hypericin. Molecular docking was used to rank the hits by testing their efficiency when bound to the target enzyme and the top three (3) selected. All three (3) of the top hits showed excellent pharmacokinetic properties but two (2) (Zinc33330198 and Zinc77235130) were identified to be non-toxic. Molecular dynamic simulation of the final two hits showed good stability, flexibility, and structural rigidity of the compounds on DNMT3B. Finally, thermodynamic energy estimations show both compounds had favourable free energies comprising − 26.04 kcal/mol for Zinc77235130 and − 15.73 kcal/mol for Zinc33330198. Amongst the final two hits, Zinc77235130 showed consistency in favourable results across all the tested parameters and was thus selected as the lead compound for further experimental validation. The identification of this lead compound will form important basis for the inhibition of aberrant DNA methylation in cancer therapy.

Demographic Factors and Their Impact on the Development of Pension System in Russia

The development of the state pension system of the Russian Federation is accomplished within the frames of Strategy-2030 and oriented towards attaining national goals and UN Targets of Sustainable Development. According to requirements of strategic documents parameters of the pension system shall be connected with basic macroeconomic and demographic indicators that can both stimulate and restrict its development. As the pension system is fully integrated in the national finance system, its functioning depends directly on finance relations between participants (employees, employers, the Pension Fund of Russia (PFR) and federal budget). However, demographic factors, such as life-span, gender structure, dynamics of birth and death, etc. act as a limiter of finance relations. The article studies changes in demographic factors and finds the trend of population aging, which could have an adverse effect on pensions of Russian citizens. Irrespective of organizational structure of the pension system and amalgamation of two biggest non-budget funds demographic problem is still an important component that affects pension provision. After-effects of the pandemic, forced relaxation and growing life expectancy of the population decreases the gap between the number of working population and the number of pensioners (coefficient of age dependence), which can result in the necessity to look for additional stimulus to the development of the pension system and raising welfare of pensioners. The goal of the article is to substantiate the trend of demographic aging of the population, which leads to higher load on the pension system.

Medicalization of sexuality and sexual health: A perspective review

Sexuality has become a medical issue in the context of aging due to a variety of aspects, such as growing life expectancy, an optimistic societal paradigm that indorses sexuality as significant for the superiority of life with age, and the medicalization of sexuality with the emergence of remedial medicines to extravagance sexual dysfunction. At any age, a reduction in the desire for sexual activity or inadequate performance of sexual intercourse is considered atypical and requires a medicinal treatment response. However, despite concerns that this is leading to an unhealthy obsession with sexuality from a medical perspective, this line of thinking is likely to continue. In this context, people can identify and take advantage of sexual problems. Sexual desire and performance are affected by normal physiological changes associated with aging in both genders. Medical experts must understand these changes to optimize sexual functioning in older patients. Sexual health can only be improved by addressing both sexual rights and enjoyment, even in the current politically charged context. Through legislation, programming, and lobbying, we may all work to enhance health, happiness, and quality of life by fostering more positive associations between sexual health, sexual rights, and sexual pleasure. This calls for not just a thorough understanding of the real-world consequences of these ideas' interconnectivity, but also conceptual, individual, and systemic approaches that properly acknowledge and alleviate the problems imposed on people's lives due to insufficient consideration of these links. This review describes the factors associated with aging and sexuality, the normalization and medicalization of sexual health, and unusual situations associated with aging, including institutionalized care and the prospects of elder abuse.

Futurization of Aging: Subjective Beliefs and Effects.

Aging in the face of an increasing population and growing life expectancy is considered one of the major demographic challenges in modern society. Previous research has revealed that quality of life in aging could significantly differ depending on the resources one possesses. However, little attention has been given to the mechanisms of formation of these resources and the role of intentionality. In the present study, we identified 22 strategies that favor a better life quality in aging and analyzed them from the perspective of subjective beliefs and reported performance. Our sample was adults (n = 72) aged 57-65, living in St. Petersburg, Russia. The results showed that although participants were aware of the strategies that favor aging, their reported performance ranged on a scale from average to infrequent use of these strategies. We found that subjective beliefs about the role of psychological resources for better aging predicted higher scores on subjective beliefs about the role of lifestyle resources and the reported performance of psychological resources. Our results suggest that there is a gap between subjective beliefs about the controllability of aging processes and the transformation of these beliefs into real performance.

Assessing Quality of Life with Community Dwelling Elderly Adults: A Mass Survey in Taiwan.

With the growing life expectancy for older adults, this study aims to examine the correlation among sociodemographic characteristics and the combined effect of QoL-related domains including physical health, psychological health, social relationships, and environmental factors with the overall QoL level of older adults in Taiwan. The WHOQOL-BREF Taiwanese Version questionnaire was adopted and conducted using a randomized telephone interview system from community household elders. In total, 1078 participants aged 65 years and older were recruited. A multiple regression model was used to examine the statistical significance between the overall QoL score as the dependent variable and the sociodemographic characteristics, and 26 items of QoL-related questionnaires as the independent variables. Categories including female, aged 85 years and above, higher education level, and better financial situation had significantly higher overall QoL level. Except the physical health domain and six items, the correlations among all other domains and their including items of questionnaires with overall QoL level were significant. The Taiwanese WHOQOL-BREF questionnaire can be used to examine the overall QoL level of elders in Taiwan. Nevertheless, the robust systems of universal health care and long-term care in Taiwan may have led to the no significance of the six items.

On the evolution of the gender gap in life expectancy at normal retirement age for OECD countries

Population aging is evolving at different rates across countries and over time, and it represents a long-term challenge for both the sustainability of pension schemes and for the realization of public intergenerational transfers. In this context, this work focuses on gender differences in survival at older ages. Specifically, we implement a comparative analysis of OECD countries to assess the adequacy of the corresponding gender-specific normal retirement age when faced with growing life expectancy. The analysis hinges on several graphical representations and is motivated by recent findings on Italian longevity to determine optimal retirement age shifts necessary to match growing life expectancy at older ages while accounting for model risk for mortality projections. Our analysis determines—at the country level—the extent to which adjustments to the normal retirement age are advisable for the sustainability of the intergenerational paradigm for pensions. The study considers males and females separately because most of these countries are characterized by aging societies where men and women have different crucial characteristics, including life expectancy. It is therefore important that policymakers have information on the future evolution of the longevity gender gap so they will be able to apply policies that preserve the principles of equality and solidarity and reduce the pension gender gap. We find groups of countries where gender gap in life expectancy follows the same dynamics.

A Multimodal Clinical Approach for the Treatment of Bone Metastases in Solid Tumors.

Bone metastasis (BM) is a frequent complication of cancer, representing the third most common site of secondary spread in solid cancers behind the lung and liver. Bone metastasis is found in up to 90% of prostate and breast cancer patients. They can cause significant complications, such as pathological fractures and paralysis of the spine, which decrease daily functioning and quality of life (QoL) and worsen prognosis. The growing life expectancy of cancer patients due to improvements in systemic therapies may further increase BM's eventuality and clinical burden in cancer patients. Four physicians from five different specialties were interviewed and resumed the most relevant literature of the last 20 years focusing on pain treatment in BM patients. Treatment for BM ideally involves various types of specialists and assessments. The disease status and patient background should be considered, requiring holistic care and expertise from various medical specialties. Interventional, nuclear medicine, radiotherapy, and mini-invasive techniques can be safe and effective for relieving pain and modifying health-related QoL in BM patients.

Diagnosing Breast Cancer Accurately Based on Weighting of Heterogeneous Classification Sub-Models

In developed and developing countries, breast cancer is one of the leading forms of cancer affecting women alike. As a consequence of growing life expectancy, increasing urbanization and embracing Western lifestyles, the high prevalence of this cancer is noted in the developed world. This paper aims to develop a novel model that diagnoses Breast Cancer by using heterogeneous datasets. The model can work as a strong decision support system to help doctors to make the right decision in diagnosing breast cancer patients. The proposed model is based on three datasets to develop three sub-models. Each sub-model works independently. The final diagnosis decision is taken by the three sub-models independently. The power of the model comes from the diversity checks of patients and this reduces the risk of wrong diagnosing. The model has been developed by conducting intensive experiments. Several classification algorithms were used to select the best one in each sub-model. As the final results, the sub-model accuracies were 72%, 74% and 97%.

Health related quality of life of the geriatric population living in rural areas of West Tripura district of India: a cross-sectional study

Growing life expectancy is challenging the quality of health care for elderly. Information regarding health related quality of life (QOL) may help policy makers to design need based health programs for this population. The objectives of this study were to estimate health related QOL of the geriatric population living in rural areas of West Tripura district and to compare it between ethnic and non-ethnic populations in respect to important domains. This community based cross-sectional study was conducted during 1st February 2019 to 31st March 2020 among 225 geriatric subjects of rural West Tripura district chosen by multistage sampling. World Health Organization’s QOL-BREF scale was used for data collection. Among the study population 46.2% had overall good health related QOL. About 52.9% had good QOL in environment and 37.3% had good QOL in social relationship domains. Marginally higher proportion of the subjects from ethnic origin had better QOL than the non-ethnic but it was not significant. Higher proportion of the Muslim subjects had better QOL than the rest, but it was also not significant. Bivariate analysis showed significant associations of QOL with age, sex, literacy, financial condition, socioeconomic status and type of family. Multivariate analysis identified male sex, younger age and living with spouse as significant predictors of good QOL. Overall health related QOL of the geriatric people living in rural areas of West Tripura district is poor but younger male subjects, of ethnic origin and living with spouse may enjoy relatively better QOL.

Citrate therapy for ur olithiasis in postmenopausal women

A tendency towards growing life expectancy in old age can be clearly observed in most countries of the world over the past number of decades. This tendency is also seen in our country. Despite the fact that people started living longer, which would seem to be a good indicator of the country’s socio-economic development, the doctors have encountered a rather difficult challenge to overcome. The question at issue is that health specialists are faced with many somatic diseases due to the fact that people started living longer. When life expectancy was much less, many of them have never encountered such a volume of diseases. Today, the share of the elderly in the population has significantly increased and they live longer, which, accordingly, has an impact on the number of nosological units in the clinical practice of almost any health specialist. This article is focused on the issue of non-decreasing incidence of urinary tract diseases; in particular, the challenges of bladder stone disease (BSD) are considered. According to the latest data, the disease prevalence does not tend to decrease. Moreover, the incidence of BSD in women has increased significantly, although this pathological condition is more typical for men. In light of the fact that female patients spend about a third of their lives in the postmenopausal period, it is worth paying special attention to some features of the woman’s body functioning during this time period due to the likelihood of the formation of an inflammatory process, which often mediates the development of the BSD. Older female patients are often concerned about inflammatory bladder diseases, which can lead to the development of BSD by ascending infection in the future. Therefore, it is crucially important to know what therapeutic capabilities doctors have today to effectively fight the BSD.

MDCT evaluation of synchronous breast carcinoma and other solid malignancies.

Multiple primary malignancies are two or more malignancies in an individual without any relationship between the tumors. The development of improved diagnostic techniques, increased survival of cancer patients and the growing life expectancy have all contributed to the increased frequency of this phenomenon. The aim of this study is to review the multidetector computed tomography (MDCT) findings of synchronous breast carcinoma and other solid malignancies. This retrospective study included 65 patients confirmed with diagnosis of synchronous breast carcinoma and other solid malignancies. CT scanning was performed using 128 MDCT in all patients. All one hundred-thirty malignancies underwent pathological evaluation. Out of 4120 patients with breast carcinoma; 65 patients were diagnosed with other synchronous primary solid malignancy. All one hundred-thirty malignancies were confirmed pathologically. Breast carcinoma detected in all 65 patients; of them metastatic breast carcinoma detected in 8 patients. Hepatocellular carcinoma was detected in 18 patients, Non-Hodgkin lymphoma (NHL) in 12 patients, endometrial carcinoma in 8 patients, uterine sarcoma in 3 patients, malignant mixed Müllerian tumor in one patient, ovarian carcinoma in 5 patients, renal cell carcinoma in 4 patients, thyroid carcinoma in 4 patients, gastric carcinoma in 2 patients, colonic carcinoma in 2 patients, ano-rectal carcinoma in one patient, hilar cholangiocarcinoma in 2 patients, malignant melanoma in 2 patients and bronchogenic carcinoma in one patient. Patients with breast carcinoma have a risk of other synchronous primary malignancy. So, careful preoperative examination is recommended to improve the patients' prognosis. MDCT scanning is accurately imaging modality for evaluation of synchronous breast carcinoma and other solid malignancies. The aim of treatment in cancer patients should always be curative even in the presence of multiple malignancies.

Where Do People Live Longer in Russia in the 21st Century? Life Expectancy across Urban and Rural areas

AbstractThe twenty‐first century marked the beginning of rapid health improvements in Russia. In the late 2000s and the 2010s, there was already a moderate decrease in inter‐oblast mortality disparities, with the exception of the growing life expectancy (LE) advantage of Moscow and Saint Petersburg. We have used newly available data to explore LE changes from 2003–2005 to 2015–2017 and determinants of LE differences across settlements of different types and population sizes. We distinguished between three major segments of the LE distribution: Moscow and Saint Petersburg at the top, large‐ and medium‐sized cities in the middle, and smaller urban and rural areas lagging behind. The LE differences among these three groups increased, but the within‐group differences decreased. The gaps between bigger cities and the “periphery” within oblasts grew, and this part of the total dispersion had increased substantially by 2015–2017. Education, together with population size, explained 62 percent (for females) and 67 percent (for males) of LE variation across 292 geographic units in 2015–2017. Our results suggest that slower health progress in small urban and rural areas is an important obstacle to further mortality reduction at the national level and is a matter of public health concern.

Integrative Role of Hyperbaric Oxygen Therapy on Healthspan, Age-Related Vascular Cognitive Impairment, and Dementia.

Growing life expectancy will contribute to the on-going shift towards a world population increasingly comprised of elderly individuals. This demographic shift is associated with a rising prevalence of age-related diseases, among all age-related pathologies it has become crucial to understand the age-associated cognitive changes that remain a major risk factor for the development of vascular cognitive impairment and dementia (VCID). Furthermore, age-related Alzheimer’s disease and other neurogenerative diseases with vascular etiology are the most prominent contributing factors for the loss of cognitive function observed in aging. Hyperbaric Oxygen Therapy (HBOT) achieves physiologic effects by increasing oxygen tension (PO2), raising oxygen tissue levels, decreasing intracranial pressure and relieving cerebral edema. Many of the beneficial effects of HBOT exert their protective effects at the level of the microcirculation. Furthermore, the microcirculation’s exquisite pervasive presence across every tissue in the body, renders it uniquely able to influence the local environment of most tissues and organs, including the brain. As such, treatments aimed at restoring aging-induced functional and structural alterations of the cerebral microcirculation may potentially contribute to the amelioration of a range of age-related pathologies including vascular cognitive impairment, Alzheimer’s disease, and vascular dementias. Despite the presented evidence, the efficacy and safety of HBOT for the treatment of age-related vascular cognitive impairment and dementia remains understudied. The present review aims to examine the existing evidence indicative of a potential therapeutic role for HBOT-induced hyperoxia against age-related cerebromicrovascular pathologies contributing to cognitive impairment, dementia and decreased healthspan in the elderly.

Immunotherapy in elderly patients

In the recent years the growing life expectancy of the population and increasing cancer burden in elderly patients substantiate the urgent need for the search of optimal cancer treatment strategies. This article provides an overview of the current literature on the efficacy and safety of checkpoint inhibitors in the elderly population. A literature search for published studies using Medline (PubMed) and Elibrary databases was performed. All studies containing data on treatment results including tumor response criteria, treatment response rate, tumor control rate, overall survival were included. Case studies, animal studies and studies containing duplicate results were excluded from the analysis. In elderly patients with cancer there is a substantial number of comorbid conditions and functional disorders, which may decrease the efficacy and modulate the tolerability of immune checkpoint inhibitors (ICI). Besides, different changes associated with immunologic ageing, including thymolysis, increase of the number of memory B-cells and a decrease of hematopoesis intensity are observed. Several studies performed a comparative analysis of efficacy and toxicity of ICIs in elderly and younger patients. In most cases similar results for efficacy and toxicity were demonstrated. To evaluate the toxicity and the influence of treatment on functional status and other important measures in geriatric population further studies of factors, influencing the tolerability and treatment response of newer ICI in elderly cancer patients are needed, including additional adverse events associated with treatment.

Molecular Mechanism of Intrahepatic Cholestasis in Sickle Cell Disease

Sickle cell disease (SCD) is an autosomal recessive genetic disorder that affects over three million people worldwide. Sickle Cell Anemia, the most common form of SCD is caused by the substitution of hydrophilic glutamic acid with hydrophobic valine at the sixth position in β-globin chain. The mutated hemoglobin (HbS) polymerizes under hypoxic conditions to promote erythrocyte sickling. Sickling promotes vaso-occlusion (ischemia) and hemolysis, which are two major pathophysiological events contributing to end organ damage. SCD patients can develop Sickle Cell Intrahepatic Cholestasis (SCIC), which is a rare but lethal form of hepatopathy. Besides SCIC, cholethiasis (gallstone formation), viral hepatitis and choledocholithiasis (stones in bile duct) have also been reported in SCD patients. The morbidity associated with sickle hepatopathy is expected to rise with growing life expectancy of SCD patients. Rescue therapies to halt the progression of sickle hepatopathy will be highly beneficial, however, development of such therapies is stalled by the lack of understanding of the molecular mechanism underlying sickle hepatopathy.We assessed the liver pathophysiology in a humanized mouse model of SCD in Townes SS mice homozygous for Hbatm1(HBA)Tow and homozygous for Hbbtm2(HBG1,HBB*)Tow). Littermate sickle cell trait mice (Townes AS mice homozygous for Hbatm1(HBA)Tow and compound heterozygous for Hbbtm2(HBG1,HBB*)Tow/Hbbtm3(HBG1,HBB)Tow) were used as control mice. Our findings reveal that SCD but not control mice developed progressive intrahepatic cholestasis with age characterized by increased level of serum bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and cholesterol. Immunohistochemical analysis of SCD mice liver revealed increased ductular reaction, inflammation, and fibrosis, which is hallmark of cholestatic liver disease. Immunoelectron microscopy revealed damage to bile canalicular structure and loss of several bile transporters from hepatocyte membrane. Remarkably, biochemical analysis revealed that intrahepatic cholestasis in SCD mice was associated with loss of Wnt signaling in hepatocytes. Our preliminary findings suggest that further studies are needed to elucidate the molecular mechanism underlying progressive cholestasis in SCD mice. Profound understanding of the regulation of cholestasis and hepatobiliary injury in SCD could potentially benefit the development of new therapies to attenuate sickle hepatopathy in SCD patients. DisclosuresNo relevant conflicts of interest to declare.