Effects of Smoking Cessation on Epigenetic Aging

Abstract “Epigenetic clocks” have become widely used to assess individual rates of biological aging. However, experimental data are limited in humans to identify potential confounding factors that may influence one’s rate of epigenetic aging and multiple health outcomes. We examined multiple epigenetic aging measures among regular smokers who quit smoking for two weeks. DNA methylation markers were assessed in both whole blood and saliva at multiple time points using a customized DNA methylation microarray. Generally, no changes in epigenetic aging rates were detected in the two week observation period with the exception of pronounced decreases over time in rate of Hannum’s clock and Extrinsic Epigenetic Age Acceleration in blood DNA. In saliva DNA, decreases over time were detected in the rates of the GrimAge and DNAmPhenoAge clocks, but we saw an increase in the rate of the Skin and Blood Clock. Additional experimental studies of other common exposures may be useful to better characterize factors that may affect the observed “rate” of epigenetic aging.

Older adults are the fastest growing subset of complex patients with high medical, behavioral, and social needs.Understanding differences in disease progression patterns between complex and non-complex older adults is critical for understanding disease risk and tailoring patient-centered interventions.We identified complex patients as those having frequent medical encounters and multiple chronic conditions within the first year of the study period and non-complex patients as the converse.This study compares the disease progression patterns of (a) complex and (b) non-complex older adults by creating disease progression networks (DPN) from claims data of 762,362 patients (mean age = 73) from 2016 to 2020.We characterized the network size and density between the complex patient DPN (C-DPN) and non-complex patient DPN (NC-DPN), and compared disease progression incidence, time-to-progression, and age-and gender-related risk.Results show that the C-DPN was denser and had a wider range of values for risk of progression compared to the NC-DPN.This implies more varied disease progression patterns occurring in the complex adults.We were also able to compare (median) time-to-progressions of diseases relative to each subpopulation and found variation in disease progression time.Furthermore, k-means clustering on the network allowed us to identify highly connected diseases involved in many disease pathways that are prevalent among older adults.(e.g., lipoprotein disorders, hypertension, major depressive disorder).Our results suggest that DPNs can be used to identify important conditions and time-points for tailoring care to the complex and non-complex older adults.

EFFECTS OF SMOKING CESSATION ON EPIGENETIC AGING
Brian Chen, 1 Weiye Wang, 1 Nichole Rigby, 1 Randal Olson, 2 and Steve Sabes, 3 1.FOXO Technologies,Minneapolis,Minnesota,United States,2. FOXO Technologies,FOXO Technologies,California,United States,3. FOXO Technologies,FOXO Technologies,Minnesota,United States "Epigenetic clocks" have become widely used to assess individual rates of biological aging.However, experimental data are limited in humans to identify potential confounding factors that may influence one's rate of epigenetic aging and multiple health outcomes.We examined multiple epigenetic aging measures among regular smokers who quit smoking for two weeks.DNA methylation markers were assessed in both whole blood and saliva at multiple time points using a customized DNA methylation microarray.Generally, no changes in epigenetic aging rates were detected in the two week observation period with the exception of pronounced decreases over time in rate of Hannum's clock and Extrinsic Epigenetic Age Acceleration in blood DNA.In saliva DNA, decreases over time were detected in the rates of the GrimAge and DNAmPhenoAge clocks, but we saw an increase in the rate of the Skin and Blood Clock.Additional experimental studies of other common exposures may be useful to better characterize factors that may affect the observed "rate" of epigenetic aging..07],51.9% female) were selected for cross-sectional analyses.Low income, being male, neighbourhood deprivation, loneliness, social isolation, short or long sleep duration, low or high BMI and smoking was associated with poor health.Walking, vigorous-intensity physical activity and more frequent alcohol intake was associated with good health.There was some evidence that airborne pollutants (PM2.5, PM10, and NO2) and noise (Lden) were associated with poor health, though findings were not consistent across all models.Our findings highlight the multifactorial nature of health, the importance of non-medical factors, such as loneliness, healthy lifestyle behaviours and weight management, and the need to examine efforts to improve health outcomes of individuals with low income.

IMPLICATIONS OF BIOLOGICAL RATES OF AGING ON HEALTHCARE EXPENDITURES AND MORBIDITY
Alix Jean Santos, 1 Xavier Eugenio Asuncion, 1 Camille Rivero-Co, 1 Maria Eloisa Ventura, 1 Reynaldo II Geronia, 1 Lauren Bangerter, 2 and Natalie Sheils, 1 1.OptumLabs, Minnetonka, Minnesota, United States, 2. OptumLabs, Eden Prairie, Minnesota, United States Understanding biological aging, which entails impeding the progressive decline of biological systems, is important in enabling older adults to live independently.However, the differences in how individuals evolve as they age suggest that aging is a process that does not progress on a singledimensional trajectory.Moreover, longitudinal studies of aging that follow a cohort of individuals over the course of several years are commonly limited by cost, attrition, and subsequently small sample size.In this study, we used a variational autoencoder to estimate multidimensional rates of aging from cross-sectional routine laboratory data of 1.4 million Americans of at least 40 years of age, collected from 2016 to 2019.We uncovered four aging dimensions that represent the following bodily functions: 1) kidney, 2) thyroid, 3) white blood cells, and 4) liver and heart.We found that fast agers along these dimensions are more likely to develop chronic diseases that are related to these bodily functions.They also had higher health care expenditures compared to the slow agers.K-means clustering of individuals based on the different aging rates revealed that clusters with higher odds of developing morbidity had the highest cost across all types of health care services.Results suggest that cross-sectional laboratory data can be leveraged as an alternative methodology to understand rates of aging along different dimensions, and analysis of their relationships with future costs can aid in the development of interventions to delay disease progression.Introduction: There is substantial literature to suggest that loneliness is a risk factor for marijuana initiation, use, and continued use into adulthood.However, these relationships have yet to be investigated among older adults.Given that recent research suggests marijuana use is increasing among older adults, the purpose of the present study was to examine loneliness and other risk factors among a national sample of older adults ages 50 years or older.Methods: A secondary data analysis was conducted on the 2018 Health and Retirement Study (HRS) was conducted (n = 1,431).The HRS is a national, biannual survey conducted in the United States to assess health, psychosocial, and demographic questions among adults ages 50 years or older.We created a loneliness scale from the available questions and assessed differences based on demographics, lifetime use, and past-year use of marijuana.Weighted analyses with cyclical tree-based hot-deck imputation were conducted.Results: A sizeable percentage (23.5%) of older adults have ever used marijuana and a considerable amount (14.8%) of adults have used marijuana in the past year.Differences were found based on sex (p <.0001), age (p <.0001), race (p <.0001), and income (p <.0001).Loneliness significantly predicted marijuana usage, with adults who reported loneliness nearly 5 times more likely to use marijuana (aOR: 4.87, 95% CI 3.89, 6.10).Discussion: The present study investigated loneliness and marijuana usage among a national sample of adults.Findings from the present study may inform behavioral health interventions, harm reduction, and gerontological health.

LONELINESS AND MARIJUANA
Health indicators examined were 81 cancer and 443 noncancer illnesses used to classify participants by health status; long-standing illness; and self-rated health.Exposures were sociodemographic (age, sex, ethnicity, education, income and deprivation), psychosocial (loneliness and social isolation), lifestyle (smoking, alcohol intake, sleep duration, BMI, physical activity and stair climbing) and environmental (air pollution, noise and residential greenspace) factors.307,378 participants (mean age = 56.1 years [SD = 8

USE AMONG OLDER ADULTS: AN EXAMINATION OF THE 2018 HEALTH AND RETIREMENT STUDY Jie
Yang, 1 and Andrew Yockey, 2 1.East Carolina University, Greenville, North Carolina, United States, 2. University of North Texas Health Science Center, Denton, Texas, United States