scholarly journals Genetic and Phenotypic Evidence for the Causal Relationship Between Aging and COVID-19

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 332-332
Author(s):  
Ranran Zhai ◽  
Timothy Pyrkov ◽  
Anastasia Shindyapina ◽  
Marco Mariotti ◽  
Peter Fedichev ◽  
...  
Keyword(s):  
Immune Cell ◽  
The Elderly ◽  
Significant Negative Correlation ◽  
Epidemiological Studies ◽  
Notch Signaling Pathway ◽  
Biological Age ◽  
Risk Of Death ◽  
Age Related ◽  
Increased Risk ◽  
Clock Models

Abstract Epidemiological studies revealed that the elderly and those with comorbidities are most susceptible to COVID-19. To understand how genetics affects the risk of COVID-19, we conducted a multi-instrument Mendelian Randomization (MR) analysis and found that the genetic variation that supports a longer life is significantly associated with the lower risk of COVID-19 infection, as well as being hospitalized after infected. The odds ratio is 0.31 (P = 9.7e-6) and 0.46 (P = 3.3e-4), respectively, per additional 10 years of life. We further applied aging clock models and detected an association between biological age acceleration and future incidence and severity of COVID-19 infection for all subjects and individuals free of chronic disease. Biological age acceleration was also significantly associated with the risk of death in COVID-19 patients. A bivariate genomic scan for age-related COVID-19 infection identified a key contribution of the Notch signaling pathway and immune system. Finally, we performed MR using 389 immune cell traits as exposure and observed a significant negative correlation between their effect on lifespan and COVID-19 risk, especially for B cell-related traits. More specifically, we discovered the lower CD19 level on B cells indicates an increased risk of COVID-19 and potentially decreases the lifespan expectancy, which is further validated in clinical data from COVID-19 patients. Our analysis suggests that the factors that accelerate aging and limit lifespan cause an increased COVID-19 risk. Thus, the interventions target these factors (e.g., reduce biological age), after further validation, may have the opportunity to reduce the risk of COVID-19.

scholarly journals Genetic and Phenotypic Evidence for the Causal Relationship Between Aging and COVID-19

2020 ◽  
Author(s):  
Kejun Ying ◽  
Ranran Zhai ◽  
Timothy V. Pyrkov ◽  
Marco Mariotti ◽  
Peter O. Fedichev ◽  
...  
Keyword(s):  
Mendelian Randomization ◽  
The Elderly ◽  
Epidemiological Studies ◽  
Notch Signaling Pathway ◽  
Biological Age ◽  
Risk Of Death ◽  
Age Related ◽  
Log Odds ◽  
Clock Models ◽  
Randomization Analysis

AbstractEpidemiological studies revealed that the elderly and those with co-morbidities are most susceptible to COVID-19. To understand how genetics affects the risk of COVID-19, we conducted a multi-instrument Mendelian randomization analysis and found that the genetic variation that supports a longer life is significantly associated with the lower risk of COVID-19 infection. The odds ratio is 0.31 (95% CI: 0.18 to 0.52; P = 9.7× 10−6) per additional 10 years of life, and 0.53 (95% CI: 0.43 to 0.65; P = 2.3 × 10−9) per unit higher log odds of surviving to the 90th percentile. On the other hand, there was no association between COVID-19 susceptibility and healthspan (the lifespan free of the top seven age-related morbidities). We further applied aging clock models and detected an association between biological age acceleration and future incidence and severity of COVID-19 infection for all subjects as well as for individuals free of chronic disease. Biological age acceleration was also significantly associated with the risk of death in COVID-19 patients. Finally, a bivariate genomic scan for age-related COVID-19 infection identified a key contribution of the Notch signaling pathway. Our analysis suggests that Notch2 expression is associated with a higher risk of COVID-19 infection, providing a druggable target. More generally, interventions that reduce biological age have the opportunity to reduce the risk of COVID-19.

scholarly journals Genetic and phenotypic analysis of the causal relationship between aging and COVID-19

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Kejun Ying ◽  
Ranran Zhai ◽  
Timothy V. Pyrkov ◽  
Anastasia V. Shindyapina ◽  
Marco Mariotti ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Immune Cell ◽  
Mendelian Randomization ◽  
Biological Age ◽  
Phenotypic Analysis ◽  
Mendelian Randomization Analysis ◽  
Age Related ◽  
Immune System Development ◽  
Increased Risk ◽  
Randomization Analysis

Abstract Background Epidemiological studies revealed that the elderly and those with comorbidities are most affected by COVID-19, but it is important to investigate shared genetic mechanisms between COVID-19 risk and aging. Methods We conducted a multi-instrument Mendelian Randomization analysis of multiple lifespan-related traits and COVID-19. Aging clock models were applied to the subjects with different COVID-19 conditions in the UK-Biobank cohort. We performed a bivariate genomic scan for age-related COVID-19 and Mendelian Randomization analysis of 389 immune cell traits to investigate their effect on lifespan and COVID-19 risk. Results We show that the genetic variation that supports longer life is significantly associated with the lower risk of COVID-19 infection and hospitalization. The odds ratio is 0.31 (P = 9.7 × 10−6) and 0.46 (P = 3.3 × 10−4), respectively, per additional 10 years of life. We detect an association between biological age acceleration and future incidence and severity of COVID-19 infection. Genetic profiling of age-related COVID-19 infection indicates key contributions of Notch signaling and immune system development. We reveal a negative correlation between the effects of immune cell traits on lifespan and COVID-19 risk. We find that lower B-cell CD19 levels are indicative of an increased risk of COVID-19 and decreased life expectancy, which is further validated by COVID-19 clinical data. Conclusions Our analysis suggests that the factors that accelerate aging lead to an increased COVID-19 risk and point to the importance of Notch signaling and B cells in both. Interventions that target these factors to reduce biological age may reduce the risk of COVID-19.

Abstract T P136: Potential Contributors to the Declining Impact of Stroke Risk Factors with Age: Implications for Stroke Epidemiology in the Elderly

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
George Howard ◽  
Mary Cushman ◽  
Maciej Banach ◽  
Brett M Kissela ◽  
David C Goff ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Stroke Risk ◽  
Multivariable Analysis ◽  
The Elderly ◽  
Stroke Risk Factors ◽  
Age Related ◽  
Increased Risk ◽  
The Impact ◽  
Age Related Changes

Purpose: The importance of stroke research in the elderly is increasing as America is “graying.” For most risk factors for most diseases (including stroke), the magnitude of association with incident events decreases at older ages. Potential changes in the impact of risk factors could be a “true” effect, or could be due to methodological issues such as age-related changes in residual confounding. Methods: REGARDS followed 27,748 stroke-free participants age 45 and over for an average of 5.3 years, during which 715 incident strokes occurred. The association of the “Framingham” risk factors (hypertension [HTN], diabetes, smoking, AFib, LVH and heart disease) with incident stroke risk was assessed in age strata of 45-64 (Young), 65-74 (Middle), and 75+ (Old). For those with and without an “index” risk factor (e.g., HTN), the average number of “other” risk factors was calculated. Results: With the exception of AFib, there was a monotonic decrease in the magnitude of the impact across the age strata, with HTN, diabetes, smoking and LVH even becoming non-significant in the elderly (Figure 1). However, for most factors, the increasing prevalence of other risk factors with age impacts primarily those with the index risk factor absent (Figure 2, example HTN as the “index” risk factor). Discussion: The impact of stroke risk factors substantially declined at older ages. However, this decrease is partially attributable to increases in the prevalence of other risk factors among those without the index risk factor, as there was little change in the prevalence of other risk factors in those with the index risk factor. Hence, the impact of the index risk factor is attenuated by increased risk in the comparison group. If this phenomenon is active with latent risk factors, estimates from multivariable analysis will also decrease with age. A deeper understanding of age-related changes in the impact of risk factors is needed.

Abstract P329: White Matter Score Does Not Predict Post-tPA Hemorrhage in Elderly Patients Evaluated Acutely via Telestroke

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Muhammad Bilal Tariq ◽  
Shekhar Khanpara ◽  
Eliana Bonfante Mejia ◽  
Liang Zhu ◽  
Christy T Ankrom ◽  
...  
Keyword(s):  
White Matter ◽  
Elderly Patients ◽  
The Elderly ◽  
Periventricular White Matter ◽  
Severe Stroke ◽  
Age Related ◽  
Increased Risk ◽  
Symptomatic Intracranial Hemorrhage ◽  
Relationship Of ◽  
Patient Presentation

Background: While tPA may be safe in the elderly, increasing age appears to augment risk of post-tPA symptomatic intracranial hemorrhage (sICH). Age-related white matter changes (ARWMC) are associated with increased sICH. Patients evaluated for acute ischemic stroke (AIS) via telestroke (TS) may not have access to MRI to allow incorporation of microbleeds in tPA decisions. We assessed if increased CT-based ARWMC was associated with increased sICH in elderly patients. Methods: Patients 80 years and older who received tPA for AIS at spoke hospitals were selected from our TS network registry from 9/2015 to 12/2018. TS spoke CT scans from patient presentation were reviewed by three of the authors for periventricular white matter (PWMC) and deep white matter (DWMC) changes. Total ARWMC score, based on the Fazekas score, was collected. Total ARWMC score was either mild (0-2), moderate (3-4), or severe (5-6). PWMC and DWMC were either mild (0-1) or moderate-severe (2-3). Logistic regression adjusted for age, sex, race, ethnicity, NIHSS and premorbid mRS was used to analyze relationship of ARWMC scores with sICH and patient-outcomes. Results: Of 241 patients, median age overall was 86 years (IQR 83-90), and 66% were female. The overall median ARWMC score was 3 (IQR 2-5). Regression analysis showed that more severe ARWMC scores did not lead to higher frequency of post-tPA ICH (moderate OR 0.57, CI 0.19-1.71; severe OR 1.32, CI 0.48-3.65) including sICH (moderate OR 0.78, CI 0.21-2.94; severe OR 2.09, CI 0.62-7.02). Similarly, severe PWMC and DWMC were not associated with increased risk of post-tPA ICH (PWMC OR 1.31, CI 0.51-3.38; DWMC OR 1.25, CI 0.52-3.01), including sICH (PWMC OR 1.61, CI 0.51-5.08; DWMC OR 1.81, CI 0.65-5.01). In our cohort, older patients had no difference in hemorrhage (ICH OR 0.93 CI 0.85-1.00: sICH OR 0.95 CI 0.86-1.04), and patients with less severe stroke were more likely to have hemorrhage (ICH OR 1.06 CI 1.02-1.10; sICH OR 1.08 CI 1.03-1.13). IRR among the CT scan readers was moderate (k=0.504). Conclusions: ARWMC scores were not associated with post-tPA ICH in the elderly. Our analysis lends support for the use of tPA despite severity of white matter disease. ARWMC should not be used to assist in tPA decision-making in elderly patients via telestroke.

scholarly journals Regenerative Medicine Approaches for Age-Related Muscle Loss and Sarcopenia: A Mini-Review

Gerontology ◽  
2017 ◽  
Vol 63 (6) ◽  
pp. 580-589 ◽  
Author(s):  
Juan Diego Naranjo ◽  
Jenna L. Dziki ◽  
Stephen F. Badylak
Keyword(s):  
Regenerative Medicine ◽  
Treatment Options ◽  
The Elderly ◽  
Signaling Molecules ◽  
Current Treatment ◽  
Muscle Physiology ◽  
Age Related ◽  
Increased Risk ◽  
And Function ◽  
Age Related Changes

Sarcopenia is a complex and multifactorial disease that includes a decrease in the number, structure and physiology of muscle fibers, and age-related muscle mass loss, and is associated with loss of strength, increased frailty, and increased risk for fractures and falls. Treatment options are suboptimal and consist of exercise and nutrition as the cornerstone of therapy. Current treatment principles involve identification and modification of risk factors to prevent the disease, but these efforts are of limited value to the elderly individuals currently affected by sarcopenia. The development of new and effective therapies for sarcopenia is challenging. Potential therapies can target one or more of the proposed multiple etiologies such as the loss of regenerative capacity of muscle, age-related changes in the expression of signaling molecules such as growth hormone, IGF-1, myostatin, and other endocrine signaling molecules, and age-related changes in muscle physiology like denervation and mitochondrial dysfunction. The present paper reviews regenerative medicine strategies that seek to restore adequate skeletal muscle structure and function including exogenous delivery of cells and pharmacological therapies to induce myogenesis or reverse the physiologic changes that result in the disease. Approaches that modify the microenvironment to provide an environment conducive to reversal and mitigation of the disease represent a potential regenerative medicine approach that is discussed herein.

Low vitamin D status is associated with hearing loss in the elderly: a cross-sectional study

2020 ◽  
Author(s):  
Betsy Szeto ◽  
Chris Valentini ◽  
Anil K Lalwani
Keyword(s):  
Vitamin D ◽  
Hearing Loss ◽  
Low Frequency ◽  
The Elderly ◽  
Vitamin D Status ◽  
Total Calcium ◽  
Mineral Density ◽  
Cross Sectional ◽  
Age Related ◽  
Increased Risk

ABSTRACT Background The elderly are at increased risk of both hearing loss (HL) and osteoporosis. Bone mineral density (BMD) has been putatively linked to HL. However, the roles of serum calcium concentrations and vitamin D status have yet to be elucidated. Objectives The purpose of this study was to examine the relation between vitamin D status, parathyroid hormone (PTH), total calcium, BMD, and HL in a nationally representative sample of elderly adults. Methods Using the NHANES (2005–2010), audiometry and BMD data of 1123 participants aged ≥70 y were analyzed in a cross-sectional manner. HL was defined as pure tone averages >25 dB HL at 500, 1000, and 2000 Hz (low frequency); 500, 1000, 2000, and 4000 Hz (speech frequency); and 3000, 4000, 6000, and 8000 Hz (high frequency) in either ear. Multivariable logistic regression was used to examine the relation between HL and total 25-hydroxyvitamin D [25(OH)D], PTH, total calcium, and BMD, adjusting for covariates. Results In multivariable analyses, total 25(OH)D < 20 ng/mL was found to be associated with greater odds of low-frequency HL (OR: 2.02; 95% CI: 1.28, 3.19) and speech-frequency HL (OR: 1.96; 95% CI: 1.12, 3.44). A 1-unit decrease in femoral neck BMD (OR: 4.55; 95% CI: 1.28, 16.67) and a 1-unit decrease in total spine BMD (OR: 6.25; 95% CI: 1.33, 33.33) were found to be associated with greater odds of low-frequency HL. Serum PTH and total calcium were not found to be associated with HL. Conclusions In the elderly, low vitamin D status was associated with low-frequency and speech-frequency HL. Low vitamin D status may be a potential risk factor for age-related HL.

scholarly journals Effects of carotenoids on human immune function

1999 ◽  
Vol 58 (3) ◽  
pp. 713-718 ◽  
Author(s):  
David A. Hughes
Keyword(s):  
Immune Function ◽  
Cell Function ◽  
Immune Cell ◽  
Antioxidant Properties ◽  
The Elderly ◽  
Causative Factor ◽  
Epidemiological Studies ◽  
Wide Range ◽  
Β Carotene

Many epidemiological studies have shown an association between diets rich in carotenoids and a reduced incidence of many forms of cancer, and it has been suggested that the antioxidant properties of these compounds are a causative factor. Attention has focused on the potential role of one specific carotenoid, β-carotene, in preventing cancer, and numerous publications have described in vitro experiments and animal studies which suggest that not only can this carotenoid protect against the development of cancer, but also several other chronic diseases. Since the immune system plays a major role in cancer prevention, it has been suggested that β-carotene may enhance immune cell function. Several human trials, using dietary β-carotene supplementation with a wide range of intakes, have been undertaken to address this hypothesis. The general conclusion of these studies is that this compound can enhance cell-mediated immune responses, particularly in the elderly. The present article will review some of these human studies and, hopefully, complement the reviews of other authors associated with the present symposium, some of whom will also describe work in this area. Potential mechanisms for the effects of carotenoids on immune function will also be reviewed. Finally, possible reasons for the failure of three major prospective studies to demonstrate a beneficial effect of β-carotene supplementation on lung cancer risk will be discussed.

Non-Nutritive Bioactive Food Constituents of Plants: Lycopene, Lutein and Zeaxanthin

2003 ◽  
Vol 73 (2) ◽  
pp. 95-100 ◽  
Author(s):  
Sies ◽  
Stahl
Keyword(s):  
The Elderly ◽  
Epidemiological Studies ◽  
Age Related Macular Degeneration ◽  
Carotenoid Pigments ◽  
Daily Consumption ◽  
Singlet Molecular Oxygen ◽  
Protective Mechanisms ◽  
Tomato Paste ◽  
Age Related ◽  
Yellow Color

Lycopene, lutein, and zeaxanthin are major carotenoids in human blood and tissues but unlike b-carotene do not contribute to vitamin A supply. These carotenoids are efficient antioxidants quenching singlet molecular oxygen which is formed in photooxidative processes and thus may contribute to the prevention of light-exposed tissue, skin and eyes, from light-induced damage. Increasing lycopene intake by daily consumption of tomato paste over a period of ten weeks provides protection against erythema formation following UV-irradiation. Lycopene and other carotenoids may be used as oral sun protectants and contribute to the maintenance of skin health. The yellow color of the macula lutea is due to the presence of the carotenoid pigments lutein and zeaxanthin. These macula carotenoids are suggested to play a role in protection against light-dependent damage. Filtering of blue light and scavenging of reactive intermediates generated in photooxidation are considered to be the underlying protective mechanisms. Epidemiological studies provide evidence that an increased consumption of lutein is associated with a lowered risk for age-related macular degeneration, a disease with increasing incidence in the elderly.

scholarly journals The impact of non-steroidal anti-inflammatory drugs use in elderly cardiovascular patients: an observational study from tertiary care in South India

2019 ◽  
Vol 7 (5) ◽  
pp. 1787
Author(s):  
Sadhna Sharma ◽  
Biju Govind ◽  
Kondal Rao
Keyword(s):  
Observational Study ◽  
Elderly Patients ◽  
Tertiary Care ◽  
The Elderly ◽  
Left Ventricular ◽  
Risk Of Death ◽  
Increased Risk ◽  
High Prevalence ◽  
One Year ◽  
The Impact

Background: Long-term use of NSAIDs, by patients having cardiovascular conditions, has shown to increase the risk of cardiovascular events and increased risk of death. Hence, the study was conducted to determine the complications related to NSAID use by the elderly patients with cardiovascular disease (CVD).Methods: The study was a single-center prospective observational study conducted November 2017 to October 2018. Elderly patients (>60 years) suffering from various CVDs and reported NSAID intake daily for at least one month were included. A questionnaire included demographic, treatment related history and complete details of NSAIDs intake including nature, dose, indication, source etc. The same questionnaire was again filled at the end of one-year follow-up.Results: A total of 100 participants were included in the study. The mean age was 72±8.6 years. Majority of the patients (93%) had hypertension, and 69% of the patient had previous MI.  Five NSAIDs (diclofenac, ibuprofen, mefenamic acid, naproxen, and ketorolac) were used routinely. At least one over the counter NSAID used was reported by 86%, 57% were prescribed at least one NSAIDs by their orthopaedics and physicians. At the end of 1-year follow-up, authors found that 71% had MI (2% increase), 4% developed reinfarction, 20% had severe left ventricular failure (4% increase), 7% had atrial fibrillation (1% increase), and 2% patients died and 63% patients reported raise in systolic blood pressure by 5mmHg.Conclusions: High prevalence of concomitant NSAID use among elderly CVD patients, which might be contributing towards increase in CVS morbidity and mortality.

scholarly journals Contemporary view of medical care of the elderly people with proximal femur fractures

2021 ◽  
pp. 186-195
Author(s):  
M. V. Belov ◽  
K. Yu. Belova
Keyword(s):  
Medical Care ◽  
Hip Fractures ◽  
Proximal Femur ◽  
Elderly Person ◽  
The Elderly ◽  
Care Organization ◽  
Risk Of Death ◽  
Femur Fractures ◽  
Increased Risk

Fractures of the proximal femur are a severe, life-threatening injury with enormous social, medical and economic consequences. Even with a well-organized system of medical care, up to 12-17% of patients die within the first year after injury, and the long-term risk of death doubles. Specially designed population-based studies in the Russian Federation have shown a high incidence of hip fractures in patients at the age of 50 and older. However, there is currently no unified system of medical care organization for all regions of Russia, which allows hospitalization and operation of patients with hip fractures during the first hours after trauma. Hip fracture in an elderly person is an absolute indication for the hospitalization. However most patients have severe comorbidities, osteoporosis, an increased risk of falls and mortality because of any reason. The main surgical treatments for hip fractures include osteosynthesis of the fracture or hip arthroplasty. It is well known that after the occurrence of any fragility fracture the risk of subsequent fractures increases by 2-3 times. To ensure the continuity of patient management, provide prescription of anti-osteoporotic drugs and long-term follow-up of patients it is necessary to manage them within the special Fracture Liaison Services (FLS). The article is devoted to the organization of medical care in patients of older age groups who have received hip fractures. A review of modern approaches to the treatment and organization of care for elderly patients with hip fractures is based on the methodological recommendations «Complex measures aimed at preventing falls and fractures in the elderly» developed in the framework of the federal project «The Older Generation», the draft national clinical guidelines «Fractures of the proximal femur», as well as the results of our own research.

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