Andras Orosz, Ph.D. with contributions from: Changhai Cui, Ph.D., I-Jen Castle, Ph.D., and Deidra Roach, M.D.

Alcohol and Aging (R01, R21; New concept addressing a priority area of the 2017-2021 NIAAA Strategic Plan)

Purpose

The purpose of this Notice of Special Interest (NOSI) is to promote research to improve our understanding of the effects of alcohol consumption on aging across different levels of biological organization including the molecular, cellular, tissue, organ, organism, and societal levels. The following broad research areas will be encouraged: 1) basic and clinical research defining the effects of alcohol consumption on lifespan, health span, and age-related diseases depending on level of alcohol consumption, drinking pattern, and duration of drinking; 2) Research to inform evidence-based guidance for identifying risk for alcohol use disorder (AUD) among older adults as well as prevention, diagnosis, and treatment of AUD in this population; and 3) Research to extend the health span of older adults who drink and decrease the health care burden of age-related diseases associated with alcohol use.

Background

People over 65 years constitute the fastest growing segment of the U.S. population with increasing alcohol consumption, particularly among women. Diagnosing AUD in this population is more difficult as symptoms may be masked by aging-related conditions. This silent epidemic represents a significant public health problem as aging is one of the biggest risk factors of chronic, non-communicable diseases that are exacerbated by alcohol. The relationship between alcohol and aging is complex. Chronic, heavy drinking contributes to accelerated and exacerbated aging-related symptoms and aging increases sensitivity to the physiological and neurobiological effects alcohol. Hence, defining the effects of alcohol consumption on lifespan and health span in the context of level of alcohol consumption, drinking pattern and duration of drinking is of paramount importance. Established biomarkers of aging including cellular senescence, telomere attrition, and the “epigenetic clock” could offer unprecedented insights to the underlying biological processes of alcohol on aging. Elucidating these biological pathways could provide targets for diagnosis, prevention and treatment of AUD among older adults.

Scope/Research Goals:

The Notice will support, but is not limited to the following research areas/topics:

General topics and organ diseases

1. Determine how alcohol consumption affects the pillars of aging: macromolecular damage, epigenetics, inflammation, adaptation to stress, protein homeostasis (proteostasis), stem cell regeneration, and metabolism.
2. Identify and model mechanisms through which alcohol contributes to infectious and non-infectious diseases and frailty in older adults.
3. Study alcohol-associated cardiac aging and its consequences: all-cause mortality, high blood pressure, congestive heart failure, arrythmias and vascular dysfunction.
4. Determine the effects of sex as a biological variable on the alcohol-aging axis.
5. Examine alcohol-induced changes in the microbiome and its metabolites in aging and age-related disease.
6. Explore the relationship between alcohol consumption and cancer in older adults.
7. Utilize aging biomarkers such as cellular senescence, telomere attrition, and the “epigenetic clock” to measure the various outcomes of alcohol on aging.

Neuroscience

1. Identify neurobiological mechanisms contributing to the influence of alcohol on healthy and pathologic brain aging across the spectrum of alcohol drinking patterns and doses.
2. Examine how alcohol modulates neuroimmune interactions and neuroinflammation associated with healthy and pathologic aging.
3. Explore how alcohol disrupts peripheral and central nervous system interactions and neurovascular function, which contributes to cognitive decline associated with aging.
4. Determine how alcohol consumption alters cognitive and behavioral changes associated with aging, dysregulates sleep, and impacts pain in aging populations.
5. Study how prenatal or adolescent alcohol exposure affects the aging process and susceptibility of aging pathologies.

Epidemiology, Prevention and Treatment

1. Develop screening vehicles, prevention, behavioral and pharmaceutical therapies targeted for older adults.
2. Investigate increased sensitivity to the effects of alcohol on balance, attention and driving that could contribute to falls, car crashes, and other unintentional injuries among older adults.
3. Examine the polypharmacy-alcohol interactions in older adults with emphasis on emerging legal and illicit drugs.
4. Identify vulnerabilities of high-risk groups among older adults including those with comorbidities, women, and those with racial, ethnic, socioeconomic, immigrant, sex/gender minority status.
5. Develop and evaluate innovative approaches to effectively communicate health effects of alcohol consumption to older adults to reduce alcohol-related adverse consequences.

Justification and Outcomes:

Older adults represent a rapidly growing segment of society with increasing alcohol consumption especially among women. Synergism between alcohol consumption and aging leads to various health problems that present a significant unmet clinical need. The outcomes of this NOSI will yield better understanding of alcohol’s effects on aging and age-related diseases and will provide guidance fordiagnosis, prevention and treatment for alcohol use disorders in older drinkers.

Grant Mechanism:

The research project activity codes R01 and R21 will be used. Collaboration may be sought with the National Institute of Aging and annual NIA AD/ADRD supplements may be utilized for collection of preliminary data for the initiation of these studies.