Sex and Age Differences in Default Mode Network Functional Correlation After Traumatic Brain Injury

Abstract The extent to which brain functional correlations (FCs) are modulated by age and sex is unknown. We studied default mode network (DMN) FC changes in 136 participants with mild traumatic brain injury (mTBI; 52 females, age range: 19 – 79 years, age μ = 42, age σ = 17; 72 participants younger than 40). Structural and functional magnetic resonance images (MRIs) were acquired ~1 week and ~6 months post-injury; the FreeSurfer Functional Analysis STream (FS-FAST) was used for group-level FC comparisons across sexes and age groups (younger vs. older than 40). FC seeds were two sub-networks of the DMN, M1 and M2, defined by the standard Yeo parcellation scheme. For M1, clusters with significant FC differences across sexes were in the right paracentral lobule, central sulcus, postcentral gyrus, superior frontal gyrus, and precentral sulcus (p = 0.0001), and in the left paracentral lobule and central sulcus (p = 0.022). For M2, clusters spanned the right postcentral gyrus, middle occipital gyrus, transverse occipital sulcus, and central sulcus (p = 0.0001), the left precuneus and inferior parietal lobe (p = 0.0096). Females either exhibited no significant FC change or underwent FC increases. Males underwent significant FC decreases within all clusters, suggesting their increased vulnerability to mTBI-related effects. Clusters whose FCs differed significantly across age groups were localized to the left superior temporal gyrus (p = 0.0078), highlighting the vulnerability of temporal regions to age effects. Future studies should explore the age × sex interaction and uncover the mechanisms for these observed findings.


GEROSCIENCE APPROACHES TO OBESITY Alessandro Bitto, and Matt Kaeberlein, University of Washington, Seattle, Washington, United States
Besides aging, obesity is the greatest risk factor for numerous chronic pathologies, including metabolic syndrome, type 2 diabetes, cardiovascular disease, hypertension, and cancer.Preventing and treating obesity would greatly reduce healthcare costs and the impact of the aging process, with estimated savings up to $145,000,000,000.Pharmacological interventions identified by geroscience may prove effective against diet-induced obesity.To test this hypothesis, we fed a 66% kcal/fat diet to nine-month-old C57Bl6/N mice for 6 weeks and treated them with either rapamycin, acarbose, or a combination thereof.Rapamycin, and to a lesser extent acarbose, prevented weight gain and fat accumulation in these mice.We detected increased expression of the Liver Activating Protein (LAP) isoform of the transcription factor CCAT/Enhancer Binding Protein β (C/EBPβ) in the liver of mice treated with rapamycin.C/EBPβ-LAP mediates some of the effects of caloric restriction on nutrient metabolism and increases lifespan in a mouse transgenic model.We tested whether independent activation of C/EBPβ-LAP would recapitulate the effects of rapamycin by treating mice on a high-fat diet with adefovir dipivoxil, a reverse transcriptase inhibitor that can activate LAP in vitro independently of mTOR inhibition.Adefovir dipivoxil reduced weight and fat mass accumulation in mice over the course of 6 weeks.Mice treated with adefovir dipivoxil showed increased expression of genes involved in β-oxidation and lipids mobilization, and reduced activation of fatty acid biosynthesis and lipid storage pathways.Our results identify C/EBPβ-LAP as a potential new target to improve lipid homeostasis in both aging and obesity.

PRE-OPERATIVE PHYSICAL FUNCTION PREDICTS POST-OPERATIVE SKELETAL MUSCLE GENE EXPRESSION IN OLD MICE
Samantha Asche-Godin, 1 Lauren Harlow, 2 Zachary Graham, 3 Weihua Huang, 4 Charles Mobbs, 5 Christopher Cardozo, 2 and Fred Ko, 2 1. Icahn School of Medicine at Mount Sinai/James J. Peters VA Medical Center,Bronx,New York,United States,2. James J. Peters VA Medical Center,Bronx,New York,United States,3. Birmingham VA Medical Center,Birmingham,Alabama,United States,4. New York Medical College,Valhalla,New York,United States,5

. Icahn School of Medicine at Mount Sinai, new york, New York, United States
In older adults, pre-operative physical function predicts post-operative outcomes.The biological mechanisms underlying vulnerability to physical decline remain poorly understood.Using a mouse model of laparotomy, we sought to identify biological correlates of post-operative function.24-month-old male C57BL/6N mice were categorized as high functioning (HF) or low functioning (LF) based on pre-operative performance on the accelerating rotarod.On post-operative days (POD) 2 and 4, LF mice had lower rotarod latency to fall times than HF mice did.Forelimb grip strength was reduced after laparotomy in both HF and LF groups on POD 1 and 3 and did not differ significantly between these groups.Whole transcriptome sequencing analysis (RNAseq) of soleus muscles collected on POD 5 showed 224 and 228 differentially expressed genes (DEGs) for HF and LF, respectively, compared to their respective controls.Only 21 DEGs were observed in both groups, including Pparα, Fst and Pla2g15.Such changes may be hallmarks of the post-surgical response in aging.Pathway analysis of DEGs using Ingenuity Pathway Analysis software (Qiagen) revealed one pathway common to HF and LF (osteoarthritis) whereas activation of GP6 signaling and apoptosis signaling was observed in HF and inhibition of PPARα/RXR activation and PPARα signaling was noted in LF.We conclude that pre-operative performance on the accelerating rotarod correlates with differences in skeletal muscle gene expression, which may contribute to the differences in functional outcomes post-operatively in HF and LF mice.Further studies are needed to delineate the roles of these signaling pathways in physical resilience to surgery.
The extent to which brain functional correlations (FCs) are modulated by age and sex is unknown.We studied default mode network (DMN) FC changes in 136 participants with mild traumatic brain injury (mTBI; 52 females, age range: 19 -79 years, age μ = 42, age σ = 17; 72 participants younger than 40).Structural and functional magnetic resonance images (MRIs) were acquired ~1 week and ~6 months post-injury; the FreeSurfer Functional Analysis STream (FS-FAST) was used for group-level FC comparisons across sexes and age groups (younger vs. older than 40).FC seeds were two sub-networks of the DMN, M1 and M2, defined by the standard Yeo parcellation scheme.For M1, clusters with significant FC differences across sexes were in the right paracentral lobule, central sulcus, postcentral gyrus, superior frontal gyrus, and precentral sulcus (p = 0.0001), and in the left paracentral lobule and central sulcus (p = 0.022).For M2, clusters spanned the right postcentral gyrus, middle occipital gyrus, transverse occipital sulcus, and central sulcus (p = 0.0001), the left precuneus and inferior parietal lobe (p = 0.0096).Females either exhibited no significant FC change or underwent FC increases.Males underwent significant FC decreases within all clusters, suggesting their increased vulnerability to mTBI-related effects.Clusters whose FCs differed significantly across age groups were localized to the left superior temporal gyrus (p = 0.0078), highlighting the vulnerability of temporal regions to age effects.Future studies should explore the age × sex interaction and uncover the mechanisms for these observed findings.

THE ROLE OF OBESITY IN FRAILTY INCIDENCE: THE SAN ANTONIO LONGITUDINAL STUDY OF AGING
Tiffany Cortes, 1 Chen-pin Wang, 2 Helen Hazuda, 2 and Sara Espinoza, 3 1.University of Texas HSC at San Antonio, San Antonio, Texas, United States, 2. UT Health San Antonio, UT Health San Antonio, Texas, United States, 3.

University of Texas Health Science Center San Antonio, San Antonio, Texas, United States
Background: Although initially conceptualized as a wasting syndrome, obesity has been associated with frailty in prior studies.The goal of this study was to examine the associations of obesity and waist circumference with frailty and determine whether they predict incident frailty in an ethnically diverse population of older Mexican Americans (MAs) and European Americans (EAs).Methods: 749 MA and EA community-dwelling older adults (65+) participated in the baseline examination of the San Antonio Longitudinal Study of Aging (SALSA), and 474 participants completed the first follow up approximately 6 years later.Frailty was classified using Fried criteria.Baseline characteristics, including body mass index (BMI) and waist circumference (WC) were summarized by frailty category (non-frail, pre-frail, frail) using ANOVA.The odds of becoming frail at follow-up by baseline BMI and WC were estimated using separate logistic regression models, adjusting for age, sex, ethnicity, diabetes, comorbidity (presence of ≥2 chronic diseases not including diabetes), baseline frailty score, and follow-up time.Results: At baseline, participants were 69 ±3 years old, 61% female, and 50% MA.BMI and WC increased with increasing frailty category (p <0.01 for both).BMI was a significant predictor of incident frailty (OR=1.08,95% confidence interval [CI]: 1.02-1.14,p=0.011).WC also predicted frailty (OR=1.03,95% CI: 1.01-1.05,p =0.017).Conclusion: These results demonstrate that BMI and WC are significant predictors of frailty.Interventions which target obesity may reduce the incidence of frailty; however, more research in this area is needed.

Global Aging
Session 9310 (Poster) that still lack basic amenities.Cultural differences in the profile, lifestyles, and needs of centenarians in Africa have yet to be documented.Using a case study design, this descriptive inquiry investigated the profiles of centenarians in Ethiopia including religion, marriage, education, occupation, income, and living arrangement.Data were generated through in-depth interviews with nine centenarians (1 woman, 8 men) and were analyzed using descriptive narrative analysis.Respondents were between 100 and 108 years old.All nine were adherents of Orthodox Christianity, had been married, and were great-grandparents.Their adult lives were marked by both residential and marital stability.The Ethiopian centenarians persevered through many losses and hardships with the help of strong community-based social networks.Unlike studies of centenarians in the Global North, most respondents were male and had strict religious upbringings.Understanding the unique profiles of centenarians in the Global South will help to inform research and practice with this growing population of the oldest-old.

COMPARISON OF CATASTROPHIC OUT-OF-POCKET MEDICAL EXPENDITURES IN THE US AND SOUTH KOREA Narae Kim, and Mireille Jacobson, University of Southern California, Los Angeles, California, United States
To date, relatively few studies have examined catastrophic out-of-pocket medical spending in the United States, especially in comparison to other high-income countries.We compared catastrophic out-of-pocket medical spending among adults age 65 and older in the United States versus South Korea, a high-income country with national health insurance that is often overlooked in cross-country comparisons.We defined catastrophic medical spending as health care expenditure for the past two years that exceeds 50% of one's annual household income.Using data from the 2016 Health and Retirement Study (HRS) and Korean Longitudinal Study of Aging (KLoSA), we performed a logistic regression to examine the factors affecting catastrophic out-of-pocket medical spending for older adults in both countries.We also performed a Blinder-Oaxaca decomposition to compare the As global aging advances, the number of centenarians worldwide is greatly increasing.Most of what is known about centenarians comes the Global North.It is not clear what factors contribute to longevity of centenarians in impoverished, mostly rural areas of Global South nations