Longevity InTime: Autonomous AI Institute. Anti-Aging Digital Health Immortality Transhumanist AI Channel

NIH awards $3.5 million to UConn to grow thymus cells from reprogrammed elderly cells The National Institutes of Health (NIH) has awarded the University of Connecticut $3.5 million over five years to develop thymus cells from reprogrammed cells of elderly individuals. The thymus, which produces immune T-cells, gradually atrophies with age, leading to weakened immunity in older adults. On October 12, the university announced that Professor Lai-Zhun Lai received the grant to lead this research. His lab will transplant these lab-grown thymus cells into aged mice to test whether they can support the development of human T-cells. Thymic atrophy begins in infancy, with epithelial tissue replaced by fat and T-cell output declining sharply over time. According to a 2018 study in PNAS, the production of new T-cells halves approximately every 16 years. This decline is considered a root cause of age-related immune deterioration: while a young person may recover from a cold in days, the same virus can cause life-threatening illness in the elderly, and vaccines are less effective. Thymic epithelial cells (TECs) create the environment where naive T-cells — those that have not yet encountered an antigen — mature. Cortical TECs select functional T-cells, while medullary TECs eliminate those that target the body’s own tissues. With age, TECs diminish in number and function, which the university identifies as a key factor in thymic decline. The age of naive helper T-cells influences immunological memory. In 2003, co-investigator Laura Haynes and colleagues demonstrated in mice that memory formed from young mice’s T-cells remained strong after a year, whereas memory from old mice’s T-cells was weak. In a 2015 paper, Lai’s lab described a protocol to convert human embryonic stem cells into TEC precursors using the proteins HOXA3 and FOXN1 — genes essential for thymus development, as mice lacking them fail to form a thymus. When transplanted into mice, these precursors matured into cortical and medullary TECs, and within 24 weeks, mouse T-cells developed in the grafted tissue. When human hematopoietic stem cells (which give rise to T-cells) were co-transplanted, functional human T-cells were also generated. Instead of using embryonic stem cells foreign to the recipient, Lai now uses induced pluripotent stem cells (iPSCs) derived from the patient’s own cells. These iPSCs can differentiate into any cell type and are less likely to be rejected. Although cells from elderly individuals carry age-related markers, French scientists showed in 2011 that reprogramming resets these signs: iPSCs from centenarians matched embryonic stem cells in telomere length and gene expression, and cells derived from them exhibited rejuvenated characteristics. The project, funded by the National Institute on Aging, tests whether thymus cells grown from iPSCs of elderly people can create a supportive environment for new T-cell maturation in an aged organism. The lab will generate TEC precursors from iPSCs and transplant them into aged, immunodeficient mice that do not reject human cells, alongside human hematopoietic stem cells. Researchers will quantify TECs and newly formed T-cells, assess their function — including by challenging animals with influenza virus — and verify that the T-cells do not auto-react against self-tissues. Separately, using mouse cells, the team will determine which developing T-cells assist in TEC maturation: preliminary experiments cited in the grant application showed that co-culturing precursors with developing T-cells helped the precursors become TECs. “Currently, there are no approaches that address T-cell immunodeficiency in the elderly,” Lai said. 🔗 Read original →