Invariant Natural Killer T Cells can be Provoked into Destroying Senescent Cells
Researchers here use the properties of a subset of natural killer T cells of the immune system in order to provoke these cells into greater activity without rousing the rest of the immune system into action. The outcome is that the activated natural killer T cells then destroy more senescent cells than would otherwise have been the case. Destroying senescent cells by any means leads to a dose-dependent degree of rejuvenation in older individuals, and that result is achieved here. This is an intriguing approach to the challenge of clearing senescent cells, and it will be interesting to watch its further development.
In a healthy state, these immune cells - known as invariant Natural Killer T (iNKT) cells - function as a surveillance system, eliminating cells the body senses as foreign, including senescent cells, which have irreparable DNA damage. But the iNKT cells become less active with age and other factors like obesity that contribute to chronic disease. The iNKT cells have two attributes that make them an especially appealing drug target. First, they all have the same receptor, which does not appear on any other cell in the body, so they can be primed without also activating other types of immune cells. Second, they operate within a natural negative feedback loop that returns them to a dormant state after a period of activity.
Researchers found they could remove senescent cells by using lipid antigens to activate iNKT cells. When they treated mice with diet-induced obesity, their blood glucose levels improved, while mice with lung fibrosis had fewer damaged cells, and they also lived longer. The results presented for iNKT cells in a mouse model of lung fibrosis offer hope for a potentially fatal disease that often leads to lung transplants. "I think this is a potential immune therapy for senescence and fibrosis. It's a fairly well tolerated therapy, and we just have to get around dosing and trials."
IIRC, it was almost a decade ago that activation of iNKT was touted as the cure for all sorts of pathologies... infections (microbes, fungi), fixing autoimmune conditions, and of course the cure for cancer. It was only a matter of time until it also fixes aging.
Btw, I doubt activation of iNKT doesn't trigger the rest of the immune system. Maybe if activation is very brief, the immune cascade that folllows can't fully develop.
i think here it is more about bringing the iNKT activity (albeit temporarily) back to youthful levels and not causing a cytokine storm. On the face value it seems if done carefully it could reduce cancer risk/incidence, SASP load and bring other benefits. Sounds interesting but not really earth shattering. But again, even a tiny improvement in the immune system might bring many extra years to the average life expectancy and health-span. So I would expect, if it works in humans, to bring statistically significant improvements but very niche improvements on individual level. A bit like reducing smoking...
A connection between senescence and stem cells is caused by a breast cancer-initiating protein
hyperactivation of the RANK pathway plays a double function in breast cells: In the early stages of cancer, it activates senescence, which has a protective effect and delays the appearance of tumors; in more advanced stages, RANK-induced senescence favors the accumulation of stem cells in the breast tissue, which promotes tumor growth and increased aggressiveness. The results of the work are published this week in the journal Developmental Cell.
It seems senolytics only target one area instead of all senescent cells. One that helps clear them in skin won't help with ones in the liver for example.
This new study claims that immune system senescent are the most dangerous and therefore research should focus on targeting those specifically
actual published study. https://www.nature.com/articles/s41586-021-03547-7