Aging and the Environment – Final Awardee Announcement

We are happy to announce a new partnership between HEALS and the Claude D. Pepper Older American’s Independence Center to fund transdisciplinary pilot grants on “Aging and the Environment”. Applications will share in the merging of each Center’s missions to increase research in aging and in environmental Health at Mount Sinai and have helped to bring non-EH researchers into the field through new transdisciplinary collaborations.  These grants are intended to fund pilot projects that will lead to further investigation, such as an NIEHS grant to fund further years of research.  


Title of Project: Beneficial effects of tailored light intervention (TLI) on cognitive function) in World Trade Center Responders, Recovery Workers, and Volunteers (WTC RRWV) cohort

Principal Investigator: Ola A. Alsalman, PhD

Co-Investigators: Rafael E. de la Hoz, MD, MPH, MSc; Mariana G. Figueiro, PhD

Project Period:  October 1, 2022– September 30, 2023

Pilot Award Amount: $65,000

Abstract: Alterations in circadian rhythms (CR) and poor sleep are susceptibility factors that increase the risk of cognitive decline in older adults1-5. Sleep is critical for optimal cognitive function, but as we age the risk of cognitive decline and sleep disturbances increases. Sleep disturbances are also a common problem among survivors of traumatizing events, such as the World Trade Center Responders, Recovery Workers, and Volunteers (WTC RRWV)6-10, who are entering an age (6th decade of life) in which sleep disturbances and cognitive impairment are becoming more clinically relevant. Growing evidence suggests that despite their relative youth, WTC responders may be at increased risk of early onset cognitive impairment typically seen at older ages11-14. The anticipated results of the proposed research are potentially transformative given the lack of data on the impact of poor sleep on cognition in this specific population, especially considering that cognitive decline—though multifactorial—can be mitigated via interventions if detected early. Light has been shown to positively impact CR and sleep in humans and has been demonstrated to be an effective, noninvasive therapeutic option to improve sleep and cognition. This proposal will seek to (1) identify the association between circadian rhythms disruptions (CRD) and cognitive impairment and (2) investigate the effect of intervention altering light exposure patterns on sleep activity parameters and cognition in aging WTC RRWV at risk of CR dysregulation. The Pittsburgh Sleep Quality Index will be used to evaluate sleep. Cognition outcomes (i.e., sustained attention, short-term memory, and inference control) will be measured using a validated computer-assisted battery of repeated game-like tasks15,16. The study’s findings will shed the light at the relationship between CRD and manifestations of cognitive deficit in an under-investigated, highly comorbid, older adult population that is at risk of adverse effects from those factors. 

Title of Project: The association between PM2.5 composition and sources and atherosclerotic cardiovascular disease mortality among older adults.

Principal Investigator (MPI):  Maayan Yitshak-Sade, PhD

Co-Investigators: Elena Colicino, PhD; Allan Just, PhD; Michael Hadley, MD; Alex Federman, MD; Liuhua Shi, Sc.D.; Joel Schwartz, PhD; Heresh Amini, PhD

Project Period: October 1, 2022– September 30, 2023

Pilot Award Amount: $20,000

Abstract: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death in the U.S., and older age is a major risk factor for developing ASCVD. Fine particulate matter (PM2.5) ranks fourth among global ASCVD mortality risk factors. Therefore, it is important to investigate its contribution to the ASCVD burden among the older population. Most studies have investigated the ASCVD effects of PM2.5 mass and did not assess the toxicity of specific components or sources. While some sources are spread across the nation, other sources are unique to specific regions and may result in differential ASCVD risk in different locations across the U.S. We propose to investigate the associations of PM2.5 chemical components, source apportioned PM2.5 exposures, and ASCVD mortality (i.e., ischemic heart disease and cerebral infarction mortality) among the largest cohort of older adults in the U.S. We will include all Medicare enrollees ≥65 (2000-2018, ~70 million) and obtain information on sociodemographic variables, chronic conditions, habits, mortality dates and causes, zip code level confounders and co-pollutants. We will link annual zip code exposures to 15 PM2.5 chemical components and confounding pollutants (i.e., nitrogen dioxide and ozone) obtained from validated spatiotemporal models using an ensemble of machine learners. (1) We will estimate the association between the mixture of 15 PM2.5 chemical components and ASCVD mortality and identify the components contributing most to ASCVD mortality risk. (2) We will estimate source apportioned PM2.5 exposures and assess the association between source-specific PM2.5 exposures and ASCVD mortality. (3) We will separate nationwide sources from sources unique to the specific U.S. regions to identify geographic inequalities in exposure to PM2.5 composition and the associated ASCVD risk. This will be the largest nationwide epidemiological study to analyze ASCVD mortality risk in the older adult population based on highly spatiotemporally resolved exposure models of 15 PM2.5 chemical components.

Title of Project: The association between the built and social environment and phenotypic age acceleration

Principal Investigator (MPI): Pablo Knobel, PhD; Maayan Yitshak-Sade, PhD

Co-Investigators: Elena Colicino, PhD; Itai Kloog; Alex Federman, MD; Charles Mobbs, PhD; Rachel Litke, PhD

Project Period: October 1, 2022– September 30, 2023

Pilot Award Amount: $20,000

Abstract: Global population aging is of public health importance, as aging is among the leading risk factors for many chronic diseases. Chronological age is not always an adequate measure of risk, as individuals’ aging processes are diverse. Biological age, however, can better reflect aging-related morbidity and mortality risk. Phenotypic age is a validated biological age measure incorporating chronological age and commonly used biomarkers from blood samples. Phenotypic age Acceleration (PhenoAgeAccel) measures the degree to which a person is younger or older than their chronological age. PhenoAgeAccel has been associated with different health outcomes, including morbidity and mortality risk. PhenoAgeAccel can be driven by the built and social environment (i.e., greenness, walkability, food environment, socioeconomic status, safety, and racial composition). These exposures influence behavior patterns, which in turn influence the development of disease risk factors and morbidity and mortality risk. We aim to investigate the association of an array of built and social environment exposures with PhenoAgeAccel. We will include New York City residents treated at Mount Sinai primary care clinics (2011-2022) who are 65 years and older and have information on all clinical lab results required to calculate PhenoAgeAccel. We will obtain information on biomarkers, sociodemographic variables, disease risk factors, and comorbidities from electronic medical records. We will link the built and social environment exposures by geocoded residential address. First, we will assess the association between each exposure separately and PhenoAgeAcce. Then, we will use a mixture analysis to assess the combined association of all exposures with PhenoAgeAcce. Finally, we will assess whether sex and race/ethnicity modify the association between the exposure mixture and PhenoAgeAccel. Considering the challenge of population aging on our social and healthcare structure, furthering our understanding of the role of modifiable environmental exposures can inform targeted intervention plans.

Title of Project: Metabolomic features in dried blood spots of offspring of women with and

without inflammatory bowel disease

Principal Investigator (MPI): Manasi Agrawal, M.S

Co-I: Inga Peter, PhD; Laura Petrick; Dinesh Kumar Barupal, PhD; Francesca Petralia, PhD; Jean-Federic Colombel, MD

Project Period: October 1, 2022– September 30, 2023

Pilot Award Amount: $20,000

Abstract: Early life exposures are critical in modulating the gut microbiome, mucosal immune function, and thereby the risk of chronic diseases later in life. Increasing data indicate the relevance of early life exposures towards later onset of inflammatory bowel disease (IBD), an immune-mediated disease of the intestinal tract which has no cure and warrant further investigation. Biological samples such as dried blood spots (DBS), which are collected routinely from all newborns on filter paper in New York state, represent an immense, untapped resource towards study of pre- and perinatal exposures. We have obtained DBS from offspring of women with and without IBD (n=47 and 37, respectively), who are enrolled in the Exploring MEChanisms Of disease traNsmission In Utero through the Microbiome (MECONIUM) study, which is a longitudinal cohort of pregnant women with and without IBD and their offspring, established at Mount Sinai since 2014, with regular data and biological sample collection. The aims of this study are the following: (1) to compare untargeted metabolomic signatures in DBS of offspring of women with and without IBD and (2) to determine if untargeted metabolomic signatures in DBS of offspring correlate with dysbiosis and with fecal calprotectin, a biomarker of intestinal inflammation, at one year of age. This study will be informative towards the role of early life exposures and downstream metabolomic effects in intestinal inflammation and microbiome perturbations. This will carry implications towards prediction and potentially prevention of IBD, as well as other immune-mediated diseases. The application of a high throughput, unbiased metabolomic analytic platform, use of DBS to decipher early life variables, and correlation with further omic data in a unique longitudinal cohort make this study innovative.

Title of Project: Metal exposures and bone health in women during reproductive aging

Principal Investigator (MPI): Elena Colicino, PhD; Lauren Petrick, PhD

Co-Investigators: Megan Niedzwiecki, PhD; Megan K. Horton, PhD, MPH; Robert O. Wright, MD, MPH; Martha María Téllez-Rojo, PhD, MSc; Marcela Tamayo-Ortiz, ScD, MSc

Period: October 1, 2022– September 30, 2023

Pilot Award Amount: $20,000

Abstract: Osteoporosis is a global health condition, largely affecting postmenopausal woman. Emerging evidence suggests that exposure to trace metals is negatively associated with bone density, pointing to a potentially modifiable risk factor for osteoporosis. Metals can also act like endocrine disrupting chemicals, altering levels of sex hormones. Since hormonal alterations, such as the loss of natural estrogens, is a major risk factor for developing osteoporosis and decrease bone quality after menopause, altered sex hormones may be a mechanistic pathway linking metal exposures to decreased bone density. However, little is known about the relationship between exposure to metals during or immediately after pregnancy, when increased bone remodelling occurs and prevention would be most effective, and their effects on bone health among women in the peri- and menopausal periods, when intervention would be most advantageous. Leveraging a subset of the Programming Research in Obesity, Growth Environment and Social Stress (PROGRESS) cohort moms, we will investigate the role of trace metals [Arsenic (As), cadmium (Cd), lead (Pb)] exposures during and after pregnancy on sex hormone postnatal trajectories and bone density 11-15 years later as the moms enter the menopausal transition. These results will provide foundational data to support an R01 application extending these analysis to the full cohort of well-characterized >600 PROGRESS women to uncover the sex hormone changes through which trace metals exposures during pregnancy and postnatally influence low bone mass density in midlife. In addition, this pilot will generate pivotal menopause questionnaire data, which will set the stage for an array of future studies in PROGRESS moms investigating this susceptible and understudied decade during female reproductive aging.

Title of Project: Risk and protective factors and MRI phenotypes of frailty associated with WTC exposure

Principal Investigator: Megan K. Horton, PhD, MPH

Co-Investigators: Fred Ko, MD; Katherine Ornstein, PhD; William Hung, MD; Elena Colicino, PhD; Ghalib Bello, PhD

Project Period:  October 1, 2022– September 30, 2023

Pilot Award Amount: $65,000

Abstract: Traumatic events and environmental exposures can accelerate the biological processes of aging, that underlie age-related morbidities. Rescue and recovery workers at the World Trade Center (WTC responders) experienced exposure to a complex mixture of traumatic and environmental stressors following the 9/11 events. In the years following the attacks, studies have documented a high level of disease burden among the WTC General Responder Cohort (GRC), including the onset of age-related morbidities presenting years before anticipated. Frailty is a geriatric syndrome characterized by physiological declines and vulnerability to adverse health outcomes. It manifests as an age-related, biological vulnerability to stressors and decreased physiological reserves limiting the capacity to maintain homeostasis. As the cohort ages, it is expected that responders will accumulate comorbidities and develop age-related syndromes at an accelerated rate, increasing frailty. There is a pressing need to characterize, assess and monitor the development of age-related syndromes, particularly for brain health among this cohort as WTC-related exposures may accelerate the trajectory of aging. In this proposal, we leverage modeling approaches and expertise developed under two recently funded NIOSH U01 projects to examine associations between WTC related exposures and frailty. In U01OH012075 (Horton), we characterize the “WTC exposome”, i.e., the mixture of WTC-related experience, traumatic and toxic exposures, mental and physical health status, socioeconomic status, and social support at the time of 9/11. In U01OH012068 (Ornstein, Ko, Hung) we developed and validated a conceptual framework to characterize WTC-related frailty, the WTC-Frailty Index (WTC-FI) based on clinical conditions, health symptoms, and performance of activities of daily living collected during WTC GRC monitoring visits. In this pilot project, we will examine how the WTC exposome associates with WTC-FI in responders. In a subset of responders, we will examine the neural underpinnings of frailty using structural and functional magnetic resonance imaging (MRI). The extent to which WTC responders’ experience associates with frailty may inform associations between psychological and environmental exposures, risk and protective factors, and neurobiological mechanisms of aging. MRI markers of frailty may aid detection and monitoring of age-related neurodegenerative diseases, specifically accelerated aging associated with traumatic disasters such as 9/11.

Title of Project: Anti-Racism and Environmental Justice Scholars Pilot Program

Principal Investigator: Malika Garg, MD, MScR; Maida Galvez, MD, MPH

Co-Investigators: Sarah Evans, PhD, MPH; Terry Thompson, MPH

Project Period:  October 1, 2022– September 30, 2023

Pilot Award Amount: $20,000

Abstract: Icahn School of Medicine at Mount Sinai works closely with residents of East Harlem in New York City, a predominantly low-income, Black and LatinX community. Redlining laws of the 1930s that led to discriminatory mortgage lending practices and racial segregation continue to shape the social determinants of health of this community. Environmental injustices are prevalent, with inequities in access to healthy foods, parks playgrounds, low quality housing stock and high exposure to violence and crime. As public health professionals, we strive to dismantle structural racism and find solutions to environmental injustices that lead to health inequities. Centering the voices of communities is critical in these efforts, however future public health leaders often do not receive practical training to obtain the skills and tools to identify, prioritize and address community concerns. Academic centers and communities need to find a way to bridge the gap between academia and real-world community impact by creating bi-directional pathways of engagement towards achieving the common goals of racial and environmental justice. While the prevalence of anti- racism and environmental justice pedagogy in academic institutions has increased, this does not always translate into public health action within the communities that are most affected. The Anti-Racism and Environmental Justice (AREJ) Scholars Program will provide opportunities for graduate students to put classroom education into action by participating in grassroots work to improve the health of communities by combatting racism and environmental injustice. Students will be partnered with members of the Stakeholders Advisory Board (SAB) from the Community Engagement Core (CEC) of the Center on Health and Environment Across the LifeSpan (HEALS) to identify areas of need for research and intervention. Students will be provided with opportunities for productive engagement with the goal of benefiting the communities. We aim to center the voices of the East Harlem community, identify the community’s needs and prioritize public health action to meet those needs.