The mission of the Mouse Phenotyping and Pathological Assessment (MPPA) Core is to provide the necessary expertise and infrastructure to assess the impact of removing senescent cells (Subproject 1) or their effects (Subprojects 2-4) on measures of physical function, body composition, immune status, and age related pathology. These outcomes of healthspan have been selected for their stand-alone importance and established relationships with frailty, disability, institutionalization, and longevity in older individuals. The ability to conduct these outcomes in mice will greatly enhance our ability to translate the basic biology of aging into clinical application;the overarching goal of the Program Project. The MPPA Core will also be responsible for the banking and distribution of tissues to organ system-based Theme Leaders, and advancing the Aging Animal Medical Record in partnership with the Administrative Core (Core A) and Systems Biology and Bioinformatics Core (Core C).

Public Health Relevance

As an integral component of the Program Project, the MPPA Core will examine whether interventions targeting senescent cells or their senescence associated secretory phenotype improve key determinants of healthspan in laboratory mice. Understanding how interventions that impact biological mechanisms of aging affect not only lifespan but disability, frailty, and onset of disease is a critical step for translational research on aging. on aging.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG041122-03
Application #
8665355
Study Section
Special Emphasis Panel (ZAG1-ZIJ-2)
Project Start
Project End
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
3
Fiscal Year
2014
Total Cost
$334,578
Indirect Cost
$100,778
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Kandhaya-Pillai, Renuka; Miro-Mur, Francesc; Alijotas-Reig, Jaume et al. (2017) TNF?-senescence initiates a STAT-dependent positive feedback loop, leading to a sustained interferon signature, DNA damage, and cytokine secretion. Aging (Albany NY) 9:2411-2435
Stout, Michael B; Steyn, Frederik J; Jurczak, Michael J et al. (2017) 17?-Estradiol Alleviates Age-related Metabolic and Inflammatory Dysfunction in Male Mice Without Inducing Feminization. J Gerontol A Biol Sci Med Sci 72:3-15
Demaria, Marco; O'Leary, Monique N; Chang, Jianhui et al. (2017) Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse. Cancer Discov 7:165-176
Palmer, Allyson K; Kirkland, James L (2016) Aging and adipose tissue: potential interventions for diabetes and regenerative medicine. Exp Gerontol 86:97-105
Zhu, Yi; Tchkonia, Tamara; Fuhrmann-Stroissnigg, Heike et al. (2016) Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell 15:428-35
Comisford, Ross; Lubbers, Ellen R; Householder, Lara A et al. (2016) Growth Hormone Receptor Antagonist Transgenic Mice Have Increased Subcutaneous Adipose Tissue Mass, Altered Glucose Homeostasis and No Change in White Adipose Tissue Cellular Senescence. Gerontology 62:163-72
Xu, Ming; Tchkonia, Tamar; Kirkland, James L (2016) Perspective: Targeting the JAK/STAT pathway to fight age-related dysfunction. Pharmacol Res 111:152-154
Schafer, Marissa J; White, Thomas A; Evans, Glenda et al. (2016) Exercise Prevents Diet-Induced Cellular Senescence in Adipose Tissue. Diabetes 65:1606-15
Baker, Darren J; Childs, Bennett G; Durik, Matej et al. (2016) Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature 530:184-9
Campisi, Judith (2016) Cellular Senescence and Lung Function during Aging. Yin and Yang. Ann Am Thorac Soc 13:S402-S406

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