The SENS Research Foundation has announced a collaboration with the Buck Institute for Research on Aging. The two foundations have collaborated a great deal in the past, and the focus of this new research is to involve cellular senescence in relation to the age-related decline of the immune system. This research was made possible through the generous support of the Forever Healthy Foundation and its founder Michael Greve as well as the community members who have donated to the SENS Research Foundation.
Cellular senescence is a safety feature
Some researchers have suggested that, because the amount of senescent cells increases with aging, cellular senescence contributes to aging. However, things are rarely as simple as they might at first seem, and this downplays what the likely primary purpose of cell senescence is. Cellular senescence is a safety measure built into cells to prevent the propagation of damaged cells, allowing them to enter apoptosis (programmed cell death) and have the immune system dispose of them. Therefore, senescence is, generally speaking, a good thing, as it keeps us safe from damaged cells causing cancer and promotes healthy tissue repair.
However, there is a tipping point of this safety checkpoint: clearing away unwanted senescent cells is the job of the immune system, and replacing the lost cells requires stem cells to repopulate the tissue. As we age, the ability of the immune system to clear these cells begins to fail, and they begin to accumulate; this, in turn, increases inflammation, reducing the ability of stem cells to replace losses, and this is what begins the downward spiral. At this point, cellular senescence ceases to be a safety checkpoint and switches to becoming an active aging process.
The age-related decline of the immune system is an important player in why we age, and one of the things that repair-based strategies, such as those proposed by the SENS Research Foundation, aim to tackle in their approach to treating age-related diseases. The immune system fights invading pathogens and helps us to overcome diseases, but, as we age, it becomes increasingly dysfunctional and unable to perform its critical job. As well as combating marauding microbes and invading viruses, it is also responsible for destroying senescent cells and disposing of the resulting cellular debris. However, as we age, the ability of the immune system to detect and dispose of damaged senescent cells begins to fail due to the accumulation of damage that the body suffers as a result of its normal operation. As a result, increasing numbers of senescent cells escape destruction.
This is one reason why cancer risk rates increase as we age: more senescent and potentially cancerous cells remain in place. Interestingly, at least some of the age-related decline of the immune system is due to the immune cells themselves becoming senescent (stem cell depletion and altered intercellular communication also influence this decline) and failing to work properly. These dysfunctional immune cells then become part of the problem, lingering and contributing to a downward spiral of inflammation and causing more healthy cells to become senescent. There is a certain amount of irony to this: the gatekeeper itself becomes a victim of the very thing it is made to watch for.
The big news
It was great to learn that the SENS Research Foundation is once again working with the Buck Institute for Research on Aging, particularly Dr. Judith Campisi. Dr. Campisi can be considered to be one of the most senior authorities on cellular senescence, with numerous publications covering the subject. We at LEAF are also proud to include Dr. Campisi on our scientific advisory board, and it is great to see her critical work once again being supported by the SENS Research Foundation.
SENS Research Foundation (SRF) has launched a new research program focused on dysfunctional white blood cells in collaboration with the Buck Institute for Research on Aging. Judith Campisi, a leading global expert on aging and age-related diseases, will be running the project in her lab at the Buck. Various types of unwanted cells accumulate during aging and affect the function of many systems, including the immune system. Some of these cells are cleared by the immune system, but some are not, possibly leading to a vicious cycle of decline. It is therefore a priority to explore techniques for eliminating these cells and rejuvenating the body, by forcing the unwanted cells to “commit suicide”, and/or by augmenting the cell-killing function of healthy immune cells.
Given the huge amount of interest in senescent cells over the past year or so, we are delighted to see yet another big step towards understanding cellular senescence and finding solutions that can be applied to people. We are reaching the point at which the weight of scientific evidence strongly supports senescent cell removal as a plausible therapy to help maintain health as we age. This is the first rejuvenation therapy based on the SENS proposal of repairing the root causes of aging to treat disease, and we are very excited by this new collaboration.
 López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.