The Ageing Cluster:

A multiomic & phenotypic map of the ageing mouse

Key features:

  1. Two mouse strains

    • Inbred C57BL/6 and genetically diverse 4-way cross HET3

  2. 4 timepoints across the lifespan

    • 6, 12, 18, 24mos

  3. Longitudinal physiological phenotyping

  4. Multiomics of 4 tissues

    • Brain, muscle, intestine, immune

  5. Development of 2 mouse models

    • Atg5-AID2 autophagy inhibition accelerated ageing

    • Cxcr4-AID2 vaccine response enhancement

Reach out to collaborate

〰️

Reach out to collaborate 〰️

Walid Khaled Cluster Lead Cambridge

Laura Greaves Cluster Lead Newcastle

Geula Hanin Ferguson-Smith Lab Cambridge

Michelle Linterman Babraham

Masashi Narita Cambridge

Dervis Salih UCL

Nick Schaum Khaled Lab Cambridge

Karen Suetterlin Newcastle

Helen Tuppen Greaves Lab Newcastle

Yaru Zhang Khaled Lab Cambridge

Mouse Cohort Design

Timeline

Biobanked Samples at Cull

Sample Preservation at Cull

Biobanked Longitudinally Terminal Assays

Longitudinal Assays

Atg5 and Cxcr4 Degron Models

Atg5

  1. Atg5 KO = lethal neurotoxicity

  2. Atg5i dox-induced RNAi

    • no BBB permeability / too severe to mimic ageing

  3. Atg5.2 = reduced RNAi

    • mimics ageing better / 240d lifespan / no BBB permeability

  4. Atg5-AID2 mouse

    • AID: Auxin-inducible degron

    • BBB permeable, but only partial degradation

    • Predict 10mo max survival: auxin @ 3mo, cull at 6, 9mos.

Cxcr4

  1. Age = ↑ CXCR4 on follicular helper T cells = impaired vaccine response

  2. Cxcr4-AID2 x IL21CRE  = vaccine response rescue?