RNA Metabolism in Aging and Healthy Lifespan

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Topic Description

Post Date: July 10, 2026

Expiration Date: July 10, 2028

The purpose of this topic is to encourage studies on the molecular mechanisms that determine the effects of RNA metabolism on aging and aging-related diseases. Research in the area of this topic will address critical mechanistic questions for the role of RNA metabolism in aging and healthspan.

Background 

The aging process encompasses a cascade of genetic information flow within cells, from DNA to RNA to protein. While traditionally seen as a linear progression, studies have unveiled a myriad of intricacies of this central dogma, highlighting the pivotal role of RNAs in cellular functions. Comprising various types such as mRNA, rRNA, tRNA, non-coding RNA, and small RNAs, RNAs serve as linchpins in cellular processes. They not only serve as template and assemble the machinery for protein synthesis but also intricately regulate gene expression. RNA metabolism generally refers to any events in the life cycle of RNAs. In this topic, RNA metabolism refers to RNA editing, RNA alternative splicing, and RNA modification. RNAs can be edited enzymatically to modify their sequences. In addition, the transcribed pre-mRNAs often have multiple options to be alternatively spliced into different isoforms of functional mRNAs. Furthermore, over 170 distinct post-transcriptional chemical modifications have been identified in cellular RNAs, affecting their functions in various ways. These RNA metabolisms have revealed more complexity in the regulation of cellular functions.  

RNA editing, alternative splicing, and RNA modification have all been implicated in the regulation of aging and longevity, yet their underlying mechanisms remain largely unknown. Recent technological advances, including DNA and RNA sequencing and detection methods of RNA modifications, offer unprecedented opportunities to dissect the complexity and specificity of the aging process, paving the way for prevention and intervention of aging-related diseases. RNAs, due to their inherent short half-life, may be better targets with less probability for adverse consequences. Furthermore, the changes in RNAs and their regulators may provide alternative therapeutic targets for those “non-druggable” proteins. The exploration under this topic holds promise for unveiling novel strategies to address age-related conditions and improve health outcomes.

This topic aims to encourage studies that would advance our understanding of RNA metabolism's pivotal roles in aging and its implications for developing strategies to combat age-related diseases. Collaborative efforts leveraging cutting-edge technologies are encouraged to drive transformative discoveries in this field.  

Participating ICOs

National Institute on Aging (NIA)

NIA encourages novel studies of RNA metabolism to identify and characterize the changes that are associated with the aging process and cause the deterioration of cellular and physiological functions in aging and aging-related diseases.

Areas of Interest (Examples)

  • Identify and characterize the changes in RNA metabolism that are associated with aging and aging-related diseases
  • Determine whether some of the changes in RNA metabolism play causal roles in the aging process or disease etiology
  • Examine the relationship between changes in RNA metabolism and aging hallmarks.
  • Assess whether some of the changes in RNA metabolism can serve as reliable biomarkers of aging or aging-related diseases
  • Explore what changes in RNA metabolism can serve as therapeutic targets to prevent or delay aging-related diseases
  • Investigate how RNA metabolism contributes to the heterogeneity in aging and aging diseases
ICO Scientific Contact:
Max Guo, Ph.D.
[email protected]

Alison Yao, Ph.D.
[email protected]

National Institute on Drug Abuse (NIDA)

Addictive substance use accelerates cellular and biological aging, which increases vulnerability to addiction. Changes in microRNA expression, altered RNA splicing, and other post-transcriptional processes have been implicated in the nexus between aging and substance use. NIDA encourages innovative studies to elucidate changes in the RNA landscape (RNAome) associated with aging and drug use.

Areas of Interest:

  • Changes in the RNAome associated with aging and drug use, including cell-specific changes in RNA splice variants, RNA covalent modifications, expression and subcellular localization of non-coding RNAs, and interactions with RNA-binding partners
  • RNA-mediated mechanisms by which aging and drug use influence each other and exacerbate HIV infection, polysubstance use, and related comorbidities
  • Identification of addiction-relevant RNA biomarkers
  • Identification of RNAs, RNA processing pathways, and their modulators to address substance use- and age-induced dysfunctions
ICO Scientific Contact:
Subramaniam Ananthan, Ph.D.
[email protected]

John Satterlee, Ph.D.
[email protected]

National Institute of Environmental Health Sciences (NIEHS)

Environmental exposures may contribute to accelerated cellular and biological aging, including through mechanisms that alter RNA metabolism. NIEHS encourages research that studies how environmentally relevant exposures can modify RNA editing, alternative splicing, RNA modification, and non-coding RNA regulation to influence aging and aging-related diseases. Environmental exposures of interest include, but are not limited to, air pollutants, pesticides, trace elements, nanomaterials and microplastics, endocrine-disrupting chemicals, contaminants of emerging concern, and environmental exposures related to extreme weather or disasters.

Areas of interest:

  • A more comprehensive characterization of changes in the RNome associated with environmental exposures across the lifespan
  • Research on RNA-mediated mechanisms by which environmental exposures influence aging and aging-related diseases
  • Identification of RNA-based biomarkers of environmental exposure linked to aging and aging-related diseases
ICO Scientific Contact:
Christopher Duncan, Ph.D.
[email protected]

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