December 25, 2004
Immune System T Cells Age More Rapidly Than B Cells?
One subcategory of immune system cells may be aging more rapidly and causing most of the problem with reduced immunocompetence in the elderly.
T cells are the weakest link in the immune systems of older people, based on a report by Eaton and colleagues in the December 20 issue of The Journal of Experimental Medicine. The authors show that old CD4 "helper" T cells cannot provide the stimulatory signals to B cells that prompt them to make antibodies. Old and young B cells, however, are equally effective if helped by young CD4 T cells. The authors think this may help explain why immunizations are less effective in the elderly.
B cell activation and antibody production are known to be impaired with age in both mice and humans, but it was not clear whether this defect is intrinsic to B cells or is a by-product of declining CD4 T cell helper functions.
Eaton and colleagues transferred young or old CD4 T cells into mice lacking their own CD4 T cells to determine which cells are responsible for the age-related decline in B cell function. They show that B cell activation and antibody production can be restored in old mice if they are infused with young CD4 T cells prior to immunization. On the flip side, young mice infused with old CD4 T cells developed antibody defects, even though their B cells were young. In other words, old B cells function like young ones if provided with signals from young helper T cells. While the mechanism is not completely clear, the authors show that old T cells can travel to the right location in the spleen of the mice, but have fewer of the surface proteins that send stimulatory signals to B cells.
We need the ability to rejuvenate T cells. We also need the ability to rejuvenate the thymus gland that plays a crucial role in immune response.
See my previous post Harmful Reduction In Immune System Cell Diversity With Age. Also, chronic stress more rapidly ages at least part of the immune system. See my post Chronic Stress Accelerates Aging As Measured By Telomere Length.
Does it seem plausible that you could improve immunity in old age by donating blood when you are young, centrifuging out and freezing the immune cells, and transfusing with them later in life? I'd like to try it in mice.
Someone else just raised the same idea to me in email. Some of my points in response:
1) What percentage of the cells would survive the unthawing?
2) Would one have to do what is normally done with bone marrow stem cell transplants for leukemics with a drug administered while hospitalized to produce the needed cells?
3) Can cells store indefinitely while frozen?
4) How many cells would be needed to provide enough diversity of antibodies?
I am also curious to know what causes the T cells to age in the first place? Primarily telomere shortening? Or accumulation of mutants in mtDNA? Or other?
Hmmm. Bone-marrow autografts as a palliative for aging. What a concept!
Unfortunately, most of us who would need them have failed to make the required deposits into the marrow banks when we were children. I think we should blame our parents for not anticipating these advances and doing the right thing in the 50's, 60's and 70's.
I hypothesize that it may not be necessary to preserve cells/tissue during an organism's youth to have access to young cells.
I would be surprised if all cells in an organism age equally. I susupect there is a statistical distribution of aging to the cells in organism, with the fraction of imperfect cells asymptotically approaching 100% as time goes on. With this in mind, I propose that it should be possible to take a large enough cell population out of the organism and find those cells in the tissue that are least aged. This of course requires the ability to somehow determine a cells biological age, an ability we currently lack (I think). Once the "youthful" cells are found, it should then be possible to culture them and inject/place them back into the organism.
I actually veiw some variant of this proposal as ultimately necessary for radical regenerative medicine to proceed. Unless you can stop the cells from aging in the first place, which given the 2nd law of thermodynamics seems to me highly unlikely.
Yes, there certainly are cells in the body that are very young overall. When some of those cells can be identified then it is likely manipulations to cause telomere-lengthening would get those cells dividing quite vigorously again.
The problem is that the telomere lengthening can't be done to all cells because some cells have mutations in genes that control cell division (e.g. in p53). So full body telomere lengthening would lead to much higher risk for cancer.
The development of cheap DNA sequencing devices is needed for testing which cell populations can safely have their telomeres lengthened.
The other imaginable alternative approach would first to be to do gene therapy to repair all genes that can mutate in ways that cause cancer or that cause some step on the road to cancer. Then do telomere lengthening.
So basically we either test cells to select cells that have no dangerous mutations or we fix all the dangerous mutations. Either way, then the telomere lengthening would be done.