Fight Aging!

Autoimmunity is the name given to a very large class of conditions in which the immune system malfunctions and attacks the body's own cells and machinery. Each different inappropriate target produces a different autoimmune condition, ranging from demyelination diseases like multiple sclerosis, in which the immune system attacks processes and molecules necessary for maintenance of the sheath of myelin that coats nerves, to inflammatory diseases such as rheumatoid arthritis, in which the most obvious damage occurs at the joints. In between lie autoimmune conditions for near every important aspect of our biochemistry. While it is true that the best known autoimmune conditions are not all that age-related - rheumatoid arthritis is noted as "a disease of young women" by some sources, for example - autoimmunity in the general sense does grow with age. The immune system is immensely complex even when working correctly, but the dark forest of the aged, dsyfunctional immune system is especially poorly mapped. New forms of autoimmunity and other immune system malfunctions are discovered on a regular basis. Look at the recent unveiling of type 4 diabetes as a more esoteric example of the age-damaged immune system causing issues in important tissues. It is a condition that is probably quite prevalent in the old, yet missed until now. There are no doubt a great many forms of autoimmune disease presently hiding in the margins of age-related frailty and medical conditions, yet to be cataloged and understood.

Given that the mapping of the immune system and the catalog of autoimmunity is so far from being complete, I would argue that we should devote more attention and funding towards shortcut therapies based on immune ablation and reconstruction. Researchers have in recent years cured known forms autoimmunity with very high dose immunosuppressant or chemotherapy regimes, wiping out the overwhelming majority of immunity cells, then allowing the body to repopulate its immune system naturally. Since the configuration of the immune system, including any mistaken tendency to attack the body's own tissues, is stored in its varied cell populations, this is roughly equivalent to wiping the slate and starting over. Though the cell and tissue damage of aging isn't addressed, only the harmful alterations to immune system configuration that have accumulated over the years, there is the potential to turn back some of the clock here. Unfortunately, while successful, the processes currently used to destroy immune cells with the necessary degree of completeness are dangerous enough, both in immediate risk of death and in long-term damage to health, to only be worth it when the autoimmune condition is very harmful. That is changing, however, with the advent of side-effect-free approaches to targeted cell killing such as the c-kit and CD47 method demonstrated earlier this year, or the approach that Oisin Biotechnologies uses to destroy senescent cells.

The important point here is that clearing and recreating the immune system doesn't just deal with the autoimmunity known to the research community. It also deals with the autoimmunity that isn't known, and scientists have good reason to believe that there is quite a lot of that still hiding in the woodwork. As an example of the type, I'll point out the research linked below, in which the authors find a correlation between (a) a form of autoimmunity targeting components of the angiotensin system, which is responsible for managing blood pressure and sodium levels, and (b) the risk and degree of age-related frailty and hypertension, or raised blood pressure. The more that your own immune system is actively sabotaging the machinery, the worse off you are, in other words, and this is just one of the more subtle cases in which this is shown to be the case. It is interesting to observe that the harmful effects of this form of autoimmunity are modestly reduced by one of the classes of drug that has come into use to lower blood pressure, angiotensin receptor blockers. Thus the benefits of this type of medicine may turn out to result in part from effects that were not at all intentional. Hypertension, of course, is tremendously damaging, and it is absolutely correct to try to reduce age-related increases in blood pressure. It drives numerous forms of cardiovascular disease, from harmful remodeling and weakening of heart tissue, to increased breakage of small blood vessels in the brain, to structural failure of large blood vessels weakened by atherosclerosis. It isn't good at all.

New Link Discovered Between Class of Rogue Autoantibodies and Poor Health Outcomes

Results of a new study led offer new evidence for a strong link between angiotensin receptor autoantibodies and increased risk of frailty. The team says a large class of common blood pressure drugs that target the angiotensin receptor, called angiotensin receptor blockers (ARBs), may help patients depending on the levels of the autoantibodies. In healthy individuals, immune cells produce proteins called antibodies that attack foreign invaders to destroy them and clear them out of the system. In contrast, with autoimmune disorders, the immune cells produce autoantibodies that target the body's own tissue. "We discovered that frail older individuals have markedly higher levels of an autoantibody against its own angiotensin system. The angiotensin system is a key hormonal system that regulates blood pressure and fluid balance. The presence of these antibodies in this subset of vulnerable older adults was associated with increased inflammatory burden, and with decline in grip strength, walking speed and increased number of falls."

Individuals with higher levels of autoantibodies were also more likely to suffer from higher blood pressure. The use of ARBs in such individuals correlated with better control of their blood pressure, suggesting a possible personalized medicine approach to high blood pressure treatment in older adults.Some older adults become frail as they age, and this frailty has been associated with chronic inflammation. To examine the relationship between autoantibody levels and frailty, the research team first recruited 255 participants ages 20 to 93 in Baltimore, Maryland. Participants were separated into two categories: 169 younger adults (ages 20 to 69) and 87 older adults (70 and older). The team measured blood levels of autoantibodies and found that older adults had nearly twice the levels of autoantibodies than the younger adults - a median of 7.3 micrograms per milliliter of blood compared to the younger adult group's median level of 3.76. The researchers then used a frailty screening tool to identify frail older adults by measuring grip strength and walking speed, and asking questions about weight loss, fatigue and levels of physical activity. Older adults with high autoantibody levels were 3.9 times more likely to be frail. For every 1 microgram per milliliter of blood increase in autoantibodies, the researchers observed a decrease in hand grip strength of 5.7 pounds. Additionally, every 1 microgram per milliliter of blood increase in autoantibodies increased the odds of falling by 30 percent.

"Building off of our knowledge that these autoantibodies cause chronic inflammation, we decided to look at a class of medications, angiotensin receptor blockers, that block inflammation and are commonly prescribed to lower blood pressure." To examine the effects of autoantibodies levels on ARBs, the team collected 20-year-old data from a second patient population in Chicago and measured patients' previously collected serum for autoantibody levels. The 60 participants were 70 to 90 years old, and half had been treated with ARBs. The researchers observed similar associations between autoantibody levels and decline in grip strength and walking speed in the Chicago population. Furthermore, for every 1 microgram per milliliter increase of autoantibodies, those not receiving ARBs lived 115 days less - approximately shortened life span by 9 percent. Chronic treatment with ARBs attenuated the autoantibodies' association with decline in grip strength and increased mortality.

Discovery and Validation of Agonistic Angiotensin Receptor Autoantibodies as Biomarkers of Adverse Outcomes

Agonistic angiotensin II type I receptor autoantibodies (AT1RaAbs) have not been associated with functional measures or risk for adverse health outcomes. AT1RaAbs could be utilized to stratify patient risk and to identify patients who can benefit from angiotensin receptor blocker (ARB) treatment. Demographic and physiologic covariates were measured in a discovery set of community dwelling adults from Baltimore (N=255) and AT1RaAb associations with physical function tests and outcomes assessed. A group from Chicago (N=60) was used for validation of associations and to explore the impact of ARB treatment.

The Baltimore group had 28 subjects with falls, 32 frail subjects and 5 deaths. Higher AT1RaAbs correlated significantly with interleukin-6, systolic blood pressure, body mass index (BMI), weaker grip strength, and slower walking speed. Individuals with high AT1RaAbs were 3.9 times more likely to be at high risk after adjusting for age. Every 1 µg/ml increase in AT1RaAbs increased the odds of falling 30% after adjusting for age, gender, BMI and blood pressure. The Chicago group had 46 subjects with falls and 60 deaths. Serum AT1RaAb levels were significantly correlated with grip strength, walking speed and falls. Every 1 µg/ml increase in AT1RaAbs, decreased time to death by 9% after adjusting for age, gender, BMI and blood pressure. Chronic treatment with ARBs was associated with better control of systolic blood pressure and attenuation of decline in both grip strength and time to death.