image: a, Experimental setup: splenocytes were collected from young CD45.1 mice; then, 20 million of these cells were injected into either young (2–3-month-old; n = 6) or old (22–24-month-old; n = 4) CD45.2 mice, followed 30 days later by the collection of spleens for analysis. b, Stacked bar chart showing a bulk flow cytometry analysis of transferred (CD45.1+CD3+CD4+CD8−) T cells in young and old mice, showing the proportions of CD62L+CD44− cells (naive cells, blue), CD44+PD1− (effector memory cells, green), Eomes+CCL5+ (CD4-Eomes, red), CD44+PD1+ (orange) and FOXP3+ cells (Treg, gray). c, Representative flow cytometry plots illustrating the proportions of CD4-Eomes (Eomes+CCL5+) out of CD4 T cells (CD3+CD4+CD8−) among transferred cells (CD45.1+) in young or old CD45.2 mice. d, Quantitative analysis of CD4-Eomes cells among transferred cells in young (n = 6) or old (n = 4) WT mice (CD45.2). e, Quantitative analysis of CD62L+CD44−, FOXP3+, CD44+PD1− and CD44+PD1+ CD4 T cells among transferred cells in young or old WT mice (CD45.2). f, Graph showing the comparison of CD4-Eomes cell percentages out of CD4+ cells between CD45.1 (young-transferred cells) and CD45.2 (old endogenous cells) in the old group (n = 4). The bars represent the mean ± s.e.m. from two independent experiments. Data were analyzed using a two-tailed Student’s t-test (unpaired in d,e and paired in f). Exact P values are presented in the figures.
Credit: Created with BioRender.com.
BEER-SHEVA, Israel, October 29, 2025 – Ben-Gurion University of the Negev's Prof. Alon Monsonego had discovered that T helper lymphocytes, a subset of immune cells which regulate immunity, undergo functional changes with age. These changes can indicate the biological age of individuals, which can be either higher or lower than their chronological age. Among these changes, the team (the labs of Prof. Monsonego and Prof. Esti Yeger-Lotem) discovered a new subset of T helper cells that accumulate with aging. However, they did not realize how important the role they play until a Japanese study of supercentenarians – those who live well past 100 – discovered their immune systems were filled with this subset of T helper cells. Now, Prof. Monsonego believes they are one of the keys to maintaining an age-appropriate immune system.
The findings, led by Dr. Yehezqel Elyahu from Prof. Monsonego's lab and in collaboration with Prof. Valery Krizhanovsky from the Weizmann Institute of Science, were published this month in Nature Aging (https://doi.org/10.1038/s43587-025-00953-8).
In the scientific world, aging is a process wherein cells fail to repair the normal wear and tear on them. As a result, people age. Specifically, senescence cells serve a physiological function when kept under proper regulation. However, when they accumulate such as occurs with aging, they can cause inflammation and damage. A certain fraction of T helper cells that accumulate with aging, surprisingly, were found to have killing properties. So, these T helper cells act to clean out the system of senescence cells. In fact, Prof. Monsonego discovered that if they lowered concentrations of these T helper cells in mice, the mice aged faster and lived for less time.
Interestingly, these unique and unexpected subset of T helper cells increase with age and play a prominent role in reducing aging.
If T helper cells change with age and are critical for the aging process, then, according to Prof. Monosonego and his team, we need to start tracking people in their 30s to assess the pace of aging as early as possible and follow the biological age of individuals so that early interventions help maintain their normal aging. A gap of decades can grow between biological and chronological ages.
"People say that to reverse aging and "rejuvenate", we need to reset their immune system like the immune systems of people in their 20s. However, our research shows that this might not be the case. People don't need a super-charged immune system; they need one that is working properly and appropriate for their stage in life. So, one of the "axioms" of how to reduce aging may be incorrect," says Prof. Monsonego.
Furthermore, the cells that they discovered can be used for the diagnostic and therapeutic strategies associated with dysregulated aging, longevity, and age-related diseases.
Prof. Monsonego is a member of The Shraga Segal Department of Microbiology, Immunology and Genetics, in the Faculty of Health Sciences at BGU as well as The School of Brain Sciences and Cognition.
Additional researchers included: Ilana Feygin, Ekaterina Eremenko, Noa Pinkas, Alon Zemer, Amit Shicht, Omer Berner, Roni Avigdory-Meiri, Anna Nemirovsky, and Keren Reshef from BGU, and Lior Roitman from Weizmann.
The research was supported by the Israel Ministry of Science and Technology (Grant no. 3-16148) and the Litwin and Gural Foundations.
Journal
Nature Aging
Method of Research
Experimental study
Subject of Research
Cells
Article Title
CD4 T cells acquire Eomesodermin to modulate cellular senescence and aging
Article Publication Date
7-Oct-2025