Pre-Clinical Research Core (PCRC)

The Pre-clinical Research Core plays a central role in the SA OAIC by providing the knowledge, skills, and technical support to assist OAIC investigators in using the common marmoset (Callithrix jacchus) as a pre-clinical model for aging interventions (mainly pharmacological). This core provides to OAIC investigators resources (including access to geriatric marmosets) and services to assist with pre-clinical translation projects, including reverse translational projects to develop novel marmoset models of age-related dysfunction.

This Core, led by Adam B. Salmon, PhD, and Cory Ross, PhD, supports pre-clinical (animal) projects that explore the basic biology of aging and evaluate interventions that target the aging process to enhance healthy aging, as well as to prevent and better treat aging-related diseases.

The Pre-Clinical Research Core can provide to OAIC investigators:

• Access to a unique colony of aging marmosets.
• Resources required for studying effects of aging interventions on marmoset healthspan.
• Tissues collected from marmosets across the age range.
• Services to assess analytical pharmacology in marmosets.
• Assistance with research training and dissemination of research as part of the mission of the OAIC.

The Core can also provide functional and physiological assessments of aging marmosets that are unavailable elsewhere as well as the applicable expertise to work with investigators on developing potential projects using aging marmosets.

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Below are outlined animal services provided by the Core

– Administration of nutritional or pharmaceutical interventions.

– Tolerability/safety of interventions.

– General physical parameters and animal monitoring.

• General morphometry (weight, height, waist, chest and appendage circumference)
• Body composition (Quantitative magnetic resonance (QMR))
• Physical performance (Strength (lower limb), gait, deficit accumulation)
• Physical activity (48 hr activity/actimeter)
• Cognitive/executive function (Detoured reach, conveyor belt)
• Glucose metabolism (Oral glucose tolerance, insulin concentrations, Hba1c)

– Hematologic assessment:

• Complete blood cell count
• Blood lipids

– Assessment of markers of healthspan

• Inflammation and immune status (T cell subsets and cytokine analysis)
• Metabolic Function (respirometry, glucose & lipid metabolism assessment)
• Cardiovascular function (blood pressure, echocardiogram)
• Sarcopenia
• Sample collection for “omic” assessment
• Resilience (marmoset resilience index)

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Accomplishments

With our support, investigators have made major advances and novel discoveries in clinical translational geroscience, including:

Ongoing assessment of the effect of rapamycin on marmoset lifespan and healthy aging.

• Long-term treatment with the mTOR inhibitor rapamycin has minor effect on clinical laboratory markers in middle-aged marmosets.
  Sills AM, Artavia JM, DeRosa BD, Ross CN, Salmon AB.
  Am J Primatol2019 Feb;81(2):e22927. doi: 10.1002/ajp.22927. Epub 2018 Oct 12.
• Aging research using the common marmoset: focus on aging interventions.
  Ross CN and Salmon AB.
  Nutr & Healthy Aging 5(2) 97-109. (2019). doi: 10.3233/NHA-180046

Identification of changes in the aging marmoset gut microbiome.

• Age-related changes in the marmoset gut microbiome.
  Reveles KR, Patel S, Forney L, Ross CN.
  Am J Primatol. 2019 Feb;81(2):e22960. doi: 10.1002/ajp.22960. Epub 2019 Feb 25.

Identification of significant functional changes in cardiovascular, immune, metabolic, and cognitive function with age in marmosets.

• Cross-sectional comparison of health-span phenotypes in young versus geriatric marmosets.
  Ross CN, Adams J, Gonzalez O, Dick E, Giavedoni L, Hodara VL, Phillips K, Rigodanzo AD, Kasinath B, Tardif SD.
  Am J Primatol. 2019 Feb;81(2):e22952. doi: 10.1002/ajp.22952. Epub 2019 Jan 21.

Pharmacological assessment of metformin and acarbose as potential longevity interventions in marmosets.

• Evaluation of the pharmacokinetics of metformin and acarbose in a the common marmoset.
  Fernandez E, Ross C, Javors M, Tardif S, Salmon AB.
  Pathobiol Aging Age Relat Dis. 2019 Aug 22;9(1):1657756. doi: 10.1080/20010001.2019.1657756. eCollection 2019.

Core Leaders

Core Co-Leader: Adam B. Salmon, PhD

Core Co-Leader: Cory Ross, PhD

Core Leader-in-Training: Juan Pablo Palavicini, PhD