Letting up senescence and inflammaging through T cells

Introduction

With the increase in human life expectancy, there is an urgent need to understand the common molecular pathways by which aging results in a progressively higher susceptibility to chronic morbidity, disability, and frailty. In the last years, immunometabolism has emerged as a new field to boost immune responses for cancer immunotherapies as well as to dampen autoimmune diseases.

Recent Discoveries

A recent discovery from my lab has revealed the critical role of T cell metabolism in accelerating the onset of age-associated diseases and multimorbidity. This finding has opened a new path to investigate the diverse T cell intrinsic and external stimuli that instruct T cell differentiation towards a dysfunctional state during aging, with the final goal of designing effective strategies to promote healthy aging.

Project Hypothesis

LetTBe will address the hypothesis that the time-dependent deterioration of T lymphocytes contributes not only to immunosenescence but also to the general aging process.

Proposed Approaches

The LetTBe project proposes to use multidisciplinary approaches to target age-associated T cells for preventing inflammaging, senescence, and age-associated multimorbidity. Our central goals are:

1. To define age-associated T cell heterogeneity with special focus on their cellular origin, clonality, metabolic vulnerabilities, and transcriptomic signatures.
2. To decode the environmental signals that are imprinted on age-associated T cells and contribute to their development.
3. To identify new strategies for targeting age-associated T cells to slow down immunosenescence and boost resilience to inflammaging, systemic senescence, and age-related multimorbidity.

Conclusion

In sum, LetTBe puts forward an ambitious but feasible program with the wide purpose of understanding the specific molecular mechanisms and metabolic requirements of age-associated T cells, with the final goal to guide new strategies to improve healthy aging.