Translational Research Branch and Programs

The program supports research to develop and validate in vitro models that recapitulate aging processes and traits of the source – organs and tissues, especially from humans. These models include but are not limited to organoids, tissue constructs, organs- and tissues-on-chips, which can aid the investigation of molecular and cellular pathways affecting aging and longevity as well as the identification and validation of aging biomarkers. A special focus of the program is to support the development, testing and validation of in vitro human 3D tissue model systems.
Topics may include but are not limited to:

• Developing and validating in vitro tissue models for biology of aging and geroscience research, with an emphasis on human cells and tissues.
  • In vitro models derived from other animals may be valuable for comparative purposes.
• Testing and validation of the models to investigate:
  • Molecular and cellular mechanisms of aging activated in response to pharmacologic or nutrient modulation of aging.
  • Genetic modulation of aging phenotypes.

Program Contact: Tiziana Cogliati, Ph.D.

The programs support research aimed at identifying compounds that reproducibly increase lifespan in laboratory animals that have been selected or bred for genotypic diversity. The program currently supports two multi-institutional studies, the Interventions Testing Program (ITP – using mice) and the Caenorhabditis Interventions Testing Program (CITP – using multiple species of Caenorhabditis). The ITP and CITP invite investigators from the research community to submit proposals for interventions to be tested for their ability to extend lifespan (ITP Application Instructions; CITP Application Instructions).

The programs also include gathering samples (ITP's exclusive Collaborative Interactions Program) that may be used in ancillary studies for better understanding of the molecular, cellular, and physiological mechanisms underlying lifespan and healthspan extension by pharmacological interventions. These may include studies that examine whether interventions prevent functional decline, and by what mechanisms. All data and standard operating procedures are available through their respective Data Coordinating Centers (ITP DCC).

Ancillary studies are encouraged. Topics may include but are not limited to:

• Mechanisms of action and efficacy of interventions that extend lifespan and healthspan, with an emphasis on uncovering shared versus exclusive molecular mechanisms (by intervention and by tissue type.)
• Interactions between pharmacological interventions and the molecular and cellular mechanisms of aging.
• The molecular and cellular basis for heterogeneity of responses to interventions.
• Translation of interventions to responses to stress in other animals, including humans.

Program Contact: Tiziana Cogliati, Ph.D. (CITP) and Jennifer Fox, Ph.D. (ITP)

The program supports basic and translational research of biological responses to stress and its impact on aging and health outcomes in adult animals. The scope of this portfolio includes molecular and cellular mechanisms of responses to environmental, chemical, molecular and/or biological stressors. The emphasis is on distinguishing hormetic from toxic stressors, and identifying the molecular basis for relative susceptibility, adaptability and/or resilience to these stressors. Both acute and chronic stressors are subjects for this program, especially those encountered in adults.

Topics may include but are not limited to:

• Investigation of the near-term and longer-term consequences of stressors on the molecular and cellular mechanisms and rates of aging.
• The use of new or existing assays or model systems to quantify resilience and/or identify unique or redundant mechanisms or biomarkers that identify and/or predict an adaptive or maladaptive stress response.
• The interactions between stress and lifespan extending interventions.

Program Contact: Jennifer Fox, Ph.D.

This program supports research on aging mechanisms across several vertebrate species, with a particular emphasis on nonhuman primates.

Topics may include but are not limited to:

• Development of underutilized vertebrates as models in basic aging and geroscience research.
• Testing findings from inbred animals in outbred laboratory animals, domestic, and/or wild populations.

Program Contact: Manuel Moro, Ph.D., D.V.M.

The program supports basic and translational research on developing cell- and engineering-based strategies to restore functions lost due to aging. It includes three major areas as listed below:

Reproductive Biology

• Molecular and cellular mechanisms regulating aging in organs and tissues of reproductive systems.

Regenerative Biology

• Engineering of tissues and biomaterials to restore function(s) lost due to aging.
• Rejuvenation research on the cellular and molecular mechanisms by which interventions impact the potential to restore function (e.g., ‘reverse’ aging).
• Stem cell aging, including mechanisms regulating changes and their functional consequences in stem cells with aging, distinct and shared features of stem cell aging in various tissues, effects of stem cell-niche interactions on aging, and mechanisms that can be activated or utilized to promote tissue regeneration or by which lifespan-extending interventions impact stem cell function.

Synthetic Biology

• Developing and applying synthetic biology technologies and strategies to aging biology research.

Program Contact: Fei Wang, Ph.D.