Immunosenescence and Ageing

For the last 15 years, the Akbar Lab has focused on mechanisms of immune decline during ageing. We have identified a key role of p38 MAP kinase signalling in regulating both nutrient and senescence-sensing pathways in human T cells. 

We also developed new technology for investigating immunity in human skin in vivo that has been adopted by other research groups in both academia and the biotech industry. Current collaborations using these methods include the University of Arizona, The Rockefeller University (New York) and the National University of Singapore. 

The interaction between clinicians and scientists leads to the translational aspects of our work. This has procured a £3.2M MRC Experimental Medicine Grant to investigate responses to recall antigen challenges in the skin of older humans after blocking p38MAP kinase.

Our experts

Collaborators

• Janet Lord, University of Birmingham
• Tao Dong, University of Oxford
• Menna Clatworthy, University of Cambridge
• David Mosser, University of Maryland
• James Krueger, The Rockefeller University
• Karolina Palucka, The Jackson Laboratory
• Paul Macaray, National University of Singapore
• Jonathan Crowston, National University of Singapore

Selected publications

1. Lanna A, Gomes DCO, Muller-Durovic B, et al. (2017). A sestrin-dependent Erk-Jnk-p38 MAPK activation complex inhibits immunity during aging. Nat Immunol. 2017;18(3):354-363.
2. Pereira BI, De Maeyer RPH, Covre LP, et al. (2020). Sestrins induce natural killer function in senescent-like CD8+ T cells. Nat Immunol. 2020;21(6):684-694.
3. Chambers ES, Vukmanovic-Stejic M, Shih BB, et al. (2021). Recruitment of inflammatory monocytes by senescent fibroblasts inhibits antigen-specific tissue immunity during human aging. Nat Aging. 2021;1(1):101-113.
4. Pearce DRR, Akarca AUU, De Maeyer RPH, Reddy V, Akbar ANN, et al. (2023) Phenotyping of lymphoproliferative tumours generated in xenografts of non-small cell lung cancer. Front. Oncol., Vol. 13.
5. Haston S, Gonzalez-Gualda E, Morsli S ... Akbar, AN, et al. (2023). Clearance of senescent macrophages ameliorates tumorigenesis in KRAS-driven lung cancer. Cancer Cell, Vol. 41 (7), pp. 1242-1260.e6.
6. Laphanuwat P, Gomes DCO, Akbar AN (2023). Senescent T cells: Beneficial and detrimental roles. Immunological Reviews, Vol 316 (1), pp. 160-175.
7. Pallett LJ, Swadling L, Diniz M, Maini AA ... Akbar A, et al. (2023). Tissue CD14+CD8+ T cells reprogrammed by myeloid cells and modulated by LPS. Nature 614, 334–342.
8. Lanna A, Vaz B, D'Ambra C, Valvo S ... Akbar AN, et al. (2022). An intercellular transfer of telomeres rescues T cells from senescence and promotes long-term immunological memory. Nat Cell Biol, 24, 1461–1474.
9. De Maeyer RPH, Akbar AN (2022). Aging and frailty immune landscape. Nat Aging 2, 280–281 (2022).
10. Fiard G, Stavrinides V, Chambers ES, Heavey S, Freeman A, Ball R, Akbar AN (2021). Cellular senescence as a possible link between prostate diseases of the ageing male. Nat Rev Urol 18, 597–610.

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