Browsing by Subject "aging"
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Item Aging and Post-Intensive Care Syndrome (PICS): A Critical Need for Geriatric Psychiatry(Elsevier, 2017) Wang, Sophia; Allen, Duane; Kheir, You Na; Campbell, Noll; Khan, Babar; Department of Psychiatry, IU School of MedicineDue to the aging of the intensive care unit (ICU) population and an improvement in survival rates after ICU hospitalization, an increasing number of older adults are suffering from long-term impairments due to critical illness, known as post-intensive care syndrome (PICS). This paper focuses on PICS-related cognitive, psychological, and physical impairments, and the impact of ICU hospitalization on families and caregivers. The authors also describe innovative models of care for PICS, and what roles geriatric psychiatrists could play in the future of this rapidly growing population.Item Aging and Post-Intensive Care Syndrome–Family (PICS-F): A Critical Need for Geriatric Psychiatry(Elsevier, 2019) Serrano, Patricia; Kheir, You Na P.; Wang, Sophia; Khan, Sikandar; Scheunemann, Leslie; Khan, Babar; Psychiatry, School of MedicinePostintensive care syndrome–family (PICS-F) describes the psychological symptoms that affect the family members of patients hospitalized in the intensive care unit (ICU) or recently discharged from the ICU. Geriatric psychiatrists should be concerned about PICS-F for several reasons. First, ICU hospitalization in older adults is associated with higher rates of cognitive and physical impairment compared with older adults hospitalized in non-ICU settings or dwelling in the community. This confers a special burden on the caregivers of these older ICU survivors compared with other geriatric populations. Second, as caregivers themselves age, caring for this unique burden can be more challenging compared with other geriatric populations. Third, evidence for models of care centered on patients with multimorbidity and their caregivers is limited. A deeper understanding of how to care for PICS and PICS-F may inform clinical practice for other geriatric populations with multimorbidity and their caregivers. Geriatric psychiatrists may play a key role in delivering coordinated care for PICS-F by facilitating timely diagnosis and interdisciplinary collaboration, advocating for the healthcare needs of family members suffering from PICS-F, and leading efforts within healthcare systems to increase awareness and treatment of PICS-F. This clinical review will appraise the current literature about the impact of critical illness on the family members of ICU survivors and identify crucial gaps in our knowledge about PICS-F among aging patients and caregivers.Item Aging negatively impacts the ability of megakaryocytes to stimulate osteoblast proliferation and bone mass(Elsevier, 2019) Maupin, Kevin A.; Himes, Evan R.; Plett, Artur P.; Chua, Hui Lin; Singh, Pratibha; Ghosh, Joydeep; Mohamad, Safa F.; Abeysekera, Irushi; Fisher, Alexa; Sampson, Carol; Hong, Jung-Min; Childress, Paul; Alvarez, Marta; Srour, Edward F.; Bruzzaniti, Angela; Pelus, Louis M.; Orschell, Christie M.; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicineOsteoblast number and activity decreases with aging, contributing to the age-associated decline of bone mass, but the mechanisms underlying changes in osteoblast activity are not well understood. Here, we show that the age-associated bone loss critically depends on impairment of the ability of megakaryocytes (MKs) to support osteoblast proliferation. Co-culture of osteoblast precursors with young MKs is known to increase osteoblast proliferation and bone formation. However, co-culture of osteoblast precursors with aged MKs resulted in significantly fewer osteoblasts compared to co-culture with young MKs, and this was associated with the downregulation of transforming growth factor beta. In addition, the ability of MKs to increase bone mass was attenuated during aging as transplantation of GATA1low/low hematopoietic donor cells (which have elevated MKs/MK precursors) from young mice resulted in an increase in bone mass of recipient mice compared to transplantation of young wild-type donor cells, whereas transplantation of GATA1low/low donor cells from old mice failed to enhance bone mass in recipient mice compared to transplantation of old wild-type donor cells. These findings suggest that the preservation or restoration of the MK-mediated induction of osteoblast proliferation during aging may hold the potential to prevent age-associated bone loss and resulting fractures.Item Aging: Cancer – an unlikely couple(Impact Journals, 2017-09-20) Hartley, Antja-Voy; Martin, Matthew; Lu, Tao; Pharmacology and Toxicology, School of MedicineItem ARTE index revisited: linking biomarkers of cardiometabolic health with free-living physical activity in postmenopausal women(American Physiological Society, 2022-04-01) Carter, Stephen J.; Baranauskas, Marissa N.; Singh,, Harshvardhan; Martins, Catia; Hunter, Gary R.; Exercise & Kinesiology, School of Health and Human SciencesActivity-related energy expenditure (AEE) correlates with physical activity volume; however, between-person differences in body size and walking economy (net V̇o2) can influence AEE. The ratio of total energy expenditure (TEE) and resting energy expenditure (REE) estimates physical activity level (PAL) relative to body mass, yet does not account for variance in walking economy. The activity-related time equivalent (ARTEwalk) circumvents such constraints by adjusting for individual-specific walking economy. Herein, we compared AEE, PAL, and ARTEwalk index in a cohort (n = 81) of postmenopausal women while examining possible associations with biomarkers of cardiometabolic health. Secondary analyses were performed on postmenopausal women dichotomized above/below age group 50th percentile for body fat percent. TEE was reduced by 10% for the thermogenesis of digestion wherein AEE was calculated by subtracting REE from adjusted TEE. PAL was calculated as the ratio of TEE/REE. AEE was divided by the mean net energy expenditure of nongraded walking to calculate the ARTEwalk index. Between-group differences were not detected for AEE or PAL. However, the ARTEwalk index revealed that participants with less adiposity were more physically active (258 ± 149 vs. 198 ± 115 min·day−1; P = 0.046; g = 0.46). AEE and PAL did not correlate with cardiorespiratory fitness or biomarkers of cardiometabolic health. Cardiorespiratory fitness (r = 0.32), arterial elasticity (r = 0.24), total cholesterol/HDL-c ratio (r = −0.22), and body fat% (r = −0.24) were correlated with ARTEwalk. The ARTEwalk index may offer utility in detecting possible differences in physical activity volume among postmenopausal women and appears better associated with cardiometabolic biomarkers compared with AEE or PAL.Item Association of TDP-43 Pathology With Domain-specific Literacy in Older Persons(Wolters Kluwer, 2019-10-01) Kapasi, Alifiya; Yu, Lei; Stewart, Christopher C.; Schneider, Julie A.; Bennett, David A.; Boyle, Patricia A.; Neurology, School of MedicineBackground Low health and financial literacy may be an early behavioral manifestation of cognitive impairment, dementia, and accumulating Alzheimer’s pathology. However, there are limited studies investigating the behavioral features associated with hyperphosphorylated transactive response DNA-binding protein-43 (TDP-43), a common age-related pathology, and even fewer studies investigating the neurobiological basis underlying low literacy in aging. Objective To test the hypothesis that TDP-43 pathology is associated with lower literacy. Methods Data came from 293 community-based older persons who were enrolled in two ongoing studies of aging. Participants completed literacy and cognitive assessments, consented to brain donation, and underwent detailed neuropathological evaluation for AD and TDP-43. Linear regression models assessed the association of TDP-43 with literacy after adjusting for demographics, and AD pathology. Post-hoc pairwise comparisons examined whether the level of literacy differed by TDP-43 stage. Results TDP-43 pathology was associated with lower literacy (estimate=−3.16; SE=0.86; p<0.001), above and beyond demographics and AD pathology, and this association persisted even after additionally adjusting for global cognition (estimate=−1.53; SE=0.74; p=0.038). Further, literacy was lower among persons with neocortical TDP-43 pathology compared to those without TDP-43 pathology. Conclusion TDP-43 pathology is associated with lower health and financial literacy in old age, above and beyond AD pathology.Item Associations of decision making abilities with blood pressure values in older adults(Wolters Kluwer, 2020-01-01) Lamar, Melissa; Wilson, Robert S.; Yu, Lei; Stewart, Christopher C.; Bennett, David A.; Boyle, Patricia A.; Neurology, School of MedicineObjectives: Decision making, key to successful aging, has implications for financial success, physical health, and well being. While poor decision making has been linked with increased risk of mortality, age-related cognitive decline, and dementia, less is known regarding its associations with chronic disease indicators. We investigated the associations of decision making with blood pressure (BP) values [i.e., SBP, mean arterial pressure (MAP), and pulse pressure (PP), separately] in a community-based cohort study of aging. Methods: Participants were 908 nondemented older adults (age ∼81 years; 75% women) from the Rush Memory and Aging Project. Decision making was measured using questions designed to simulate materials used in financial and healthcare settings in the real world and yielded a total score and domain-specific health and financial decision making scores. Two seated and one standing BP measurement were taken with all three contributing to average SBP, MAP that is, [SBP + (2 × DBP)]/3, and PP, that is, SBP − DBP. Participants were queried about hypertension status and antihypertension medications were visually inspected and coded. Participants also underwent medical history and cognitive assessments. Results: In separate multivariable linear regression models, total decision making scores were inversely associated with SBP, MAP, and PP after adjusting for age, sex, education, antihypertension medication use, diabetes, and cumulative cardiovascular disease burden (P values = 0.03). Decision making remained associated with these BP values after additional adjustment for global cognition. Conclusion: Poorer decision making is associated with higher BP values in nondemented older adults.Item Attenuation of epigenetic regulator SMARCA4 and ERK-ETS signaling suppresses aging-related dopaminergic degeneration(Wiley, 2020-08-04) Sun, Ling; Zhang, Jie; Chen, Wenfeng; Chen, Yun; Zhang, Xiaohui; Yang, Mingjuan; Xiao, Min; Ma, Fujun; Yao, Yizhou; Ye, Meina; Zhang, Zhenkun; Chen, Kai; Chen, Fei; Ren, Yujun; Ni, Shiwei; Zhang, Xi; Yan, Zhangming; Sun, Zhi-Rong; Zhou, Hai-Meng; Yang, Hongqin; Xie, Shusen; Haque, M. Emdadul; Huang, Kun; Yang, Yufeng; Medical and Molecular Genetics, School of MedicineHow complex interactions of genetic, environmental factors and aging jointly contribute to dopaminergic degeneration in Parkinson's disease (PD) is largely unclear. Here, we applied frequent gene co‐expression analysis on human patient substantia nigra‐specific microarray datasets to identify potential novel disease‐related genes. In vivo Drosophila studies validated two of 32 candidate genes, a chromatin‐remodeling factor SMARCA4 and a biliverdin reductase BLVRA. Inhibition of SMARCA4 was able to prevent aging‐dependent dopaminergic degeneration not only caused by overexpression of BLVRA but also in four most common Drosophila PD models. Furthermore, down‐regulation of SMARCA4 specifically in the dopaminergic neurons prevented shortening of life span caused by α‐synuclein and LRRK2. Mechanistically, aberrant SMARCA4 and BLVRA converged on elevated ERK‐ETS activity, attenuation of which by either genetic or pharmacological manipulation effectively suppressed dopaminergic degeneration in Drosophila in vivo. Down‐regulation of SMARCA4 or drug inhibition of MEK/ERK also mitigated mitochondrial defects in PINK1 (a PD‐associated gene)‐deficient human cells. Our findings underscore the important role of epigenetic regulators and implicate a common signaling axis for therapeutic intervention in normal aging and a broad range of age‐related disorders including PD.Item Cdkn2a (Arf) loss drives NF1-associated atypical neurofibroma and malignant transformation(Oxford, 2019-08) Rhodes, Steven D.; He, Yongzheng; Smith, Abbi; Jiang, Li; Lu, Qingbo; Mund, Julie; Li, Xiaohong; Bessler, Waylan; Qian, Shaomin; Dyer, William; Sandusky, George E.; Horvai, Andrew E.; Armstrong, Amy E.; Clapp, D. Wade; Pediatrics, School of MedicinePlexiform neurofibroma (PN) tumors are a hallmark manifestation of neurofibromatosis type 1 (NF1) that arise in the Schwann cell (SC) lineage. NF1 is a common heritable cancer predisposition syndrome caused by germline mutations in the NF1 tumor suppressor, which encodes a GTPase-activating protein called neurofibromin that negatively regulates Ras proteins. Whereas most PN are clinically indolent, a subset progress to atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP) and/or to malignant peripheral nerve sheath tumors (MPNSTs). In small clinical series, loss of 9p21.3, which includes the CDKN2A locus, has been associated with the genesis of ANNUBP. Here we show that the Cdkn2a alternate reading frame (Arf) serves as a gatekeeper tumor suppressor in mice that prevents PN progression by inducing senescence-mediated growth arrest in aberrantly proliferating Nf1−/− SC. Conditional ablation of Nf1 and Arf in the neural crest-derived SC lineage allows escape from senescence, resulting in tumors that accurately phenocopy human ANNUBP and progress to MPNST with high penetrance. This animal model will serve as a platform to study the clonal development of ANNUBP and MPNST and to identify new therapies to treat existing tumors and to prevent disease progression.Item Cellular senescence in aging and osteoarthritis(Taylor & Francis, 2016) Toh, Wei Seong; Brittberg, Mats; Farr, Jack; Foldager, Casper Bindzus; Gomoll, Andreas H.; Hui, James Hoi Po; Richardson, James B.; Roberts, Sally; Spector, Myron; Department of Orthopaedic Surgery, IU School of MedicineIt is well accepted that age is an important contributing factor to poor cartilage repair following injury, and to the development of osteoarthritis. Cellular senescence, the loss of the ability of cells to divide, has been noted as the major factor contributing to age-related changes in cartilage homeostasis, function, and response to injury. The underlying mechanisms of cellular senescence, while not fully understood, have been associated with telomere erosion, DNA damage, oxidative stress, and inflammation. In this review, we discuss the causes and consequences of cellular senescence, and the associated biological challenges in cartilage repair. In addition, we present novel strategies for modulation of cellular senescence that may help to improve cartilage regeneration in an aging population.