Science

Breakthrough study finds age-related cognitive decline may be reversible

Breakthrough study finds age-r...
Stanford researchers suggest that if their findings are transferable to humans they could lead to new therapies that battle age-related cognitive decline
Stanford researchers suggest that if their findings are transferable to humans they could lead to new therapies that battle age-related cognitive decline
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Stanford researchers suggest that if their findings are transferable to humans they could lead to new therapies that battle age-related cognitive decline
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Stanford researchers suggest that if their findings are transferable to humans they could lead to new therapies that battle age-related cognitive decline

A breakthrough study from a team of neurologists at Stanford University claims to have discovered one way immune cells become dysfunctional as we age, leading to the inflammatory hyperdrive that plays a role in most age-related disease from cancer to cognitive decline. Preliminary study suggests this immune dysfunction can be reversed, pointing to compelling future anti-aging therapies.

As we age, our immune system slowly grows increasingly dysfunctional. For some that means the immune system can be slower to respond to infection, and for others it means defective immune cells begin to consistently attack healthy cells, causing chronic low-grade inflammation. Some researchers hypothesize this chronic inflammation plays a major role in many age-related diseases, particularly in the brain.

So this new research started out with some general questions. What could be causing this age-related immune dysfunction? Does this chronic inflammatory activity play a role in age-related cognitive decline? And, perhaps most importantly, can this mechanism be either slowed, or reversed?

The specific focus of the new study, published in the journal Nature, was a hormone called prostaglandin E2 (PGE2). Levels of this particular hormone have previously been found to rise with aging. PGE2 is also known to promote inflammatory activity in immune cells.

The first part of the research unpacked exactly how PGE2 initiates inflammatory activity in macrophages, a fundamental immune white blood cell. Across animal experiments and in vitro human cell tests the researchers uncovered a comprehensive chain of events showing how PGE2 directly triggers dysfunctional inflammatory activity in macrophages.

The researchers then confirmed, again in both mouse and human cells, that older macrophages produce significantly more PGE2 than their younger counterparts. Alongside that, these aging macrophages present with greater surface numbers of EP2 receptors, the receptors that bind PGE2.

Katrin Andreasson, senior author on the new study, calls this age-induced inflammatory mechanism, “a double-whammy – a positive feedback loop.”

The final part of the research explored what happens when you inhibit this PGE2-EP2 mechanism. Initial in vitro experiments revealed old macrophage cells transforming when this mechanism was disrupted. Inflammatory characteristics disappeared and the old cells were effectively rejuvenated.

Inhibiting this mechanism in aged mouse models of cognitive decline resulted in even more impressive results. The old mice, receiving an experimental drug that blocks PGE2-EP2 binding, displayed a reversal of cognitive decline, ultimately performing as well as young mice across a series of cognitive tests.

Andreasson suggests this mechanism of modulating the immune system can essentially “de-age the brain.” Even when PGE2-EP2 binding was isolated to cells outside of the brain, using a compound that cannot cross the blood-brain barrier, cognitive improvements and reductions in neural inflammation were still detected.

Researchers not involved with the new study have variously described the novel research as “well-conducted”, “intriguing”, and “important”. But they also suggest it is a very preliminary finding and needs validation in humans before we can even consider being close to an anti-aging or anti-dementia therapy.

“This study is important because it shows that in mice, age-related memory decline can be reversed,” explains Tara Spires-Jones from the University of Edinburgh, “however, it is important to note that this research was in small groups of mice and more work will need to be done to determine whether the same effects will be possible in people.”

Andreasson is clear in noting the long research path that lies ahead. The experimental drugs used in the study to block PGE2-EP2 binding, for example, are not at all ready for human clinical use. In fact, they may not even be safe for humans, Andreasson suggests.

Instead, the study offers researchers new directions for developing novel compounds that can disrupt this dysfunctional age-related inflammatory activity. It may be a long time before a tangible anti-aging clinical therapy arises from these findings but, if validated, these foundational discoveries offer an exciting road map for producing therapies that could battle a broad array of age-related diseases.

“Our study suggests that cognitive aging is not a static or irrevocable condition but can be reversed by reprogramming myeloid glucose metabolism to restore youthful immune functions,” the researchers conclude in the new study.

The new study was published in the journal Nature.

Source: Stanford University

15 comments
15 comments
Nobody
This will probably be released right after the cure for cancer, the common cold and controlled nuclear fusion. Take your flying car to the nearest pharmacy to get your $2 prescription.
guzmanchinky
Given that my mother just died of dementia at 80 and I'm 50, this is important science for me...
Nobody
@guzmanchinky, I'm sorry for your loss. My sarcastic comment was aimed at all the so called scientific break throughs we read about every week that are just hype and will never come to pass.
Nick Arrizza
Has anyone heard of the work of Drs Dean and Ayesha Sherzai who have shown that up to 90% of Alzheimer's cases can be prevented and even reversed (in early stages) with a 100% whole food plant based diet? This information has been around for at least a decade yet the medical establishment focused on pharmacological treatments is blinded by their own inadequate training in the major impact of nutrition and lifestyle on the prevention and reversal of up to 80% of all chronic diseases (which we have known for over 100 years from evidence based research that has essentially bee ignored)!
Catweazle
Put me down for a double dose!
Y_Contributor
Metformin, a drug approved by the Food and Drug Administration used for the treatment of type 2 diabetes, inhibits PGE2 production, and reduces both inflammation and the potential for cancer.
buzzclick
@guzmanchinky, I too recently lost my mom who had developed some dementia. I only just discovered that this disease happens mostly to women. This could be because they generally live longer, watch more TV and perhaps exercise less. It's been some years now that all this attention is paid towards inflammation and its consequences.

It may be some time before drugs are developed to control prostaglandin levels but my personal approach is to eat more fruit, vegetables and legumes and less meat, exercise your body to oxygenate your blood better and mental workouts to challenge your brain and keep it on its toes. There are no guarantees, but that should improve the odds.
Nobody
@Y_Contributor, metformin is not as safe as you might think. I know two older folks who nearly died from using it because they had limited kidney function and the doctor prescribed it anyway. It has also been connected to heart disease, Alzheimer's disease and Parkinson's disease. This is a drug that has many possible serious side effects and should be used with extreme caution especially if you are elderly.
@Nick Arrizza, you are absolutely correct about nutrition. Modern medical research has just recently awakened to the fact that nutrition and our own gut bacteria are critical to our health and immune system. Yet, many if not most doctors are woefully ignorant of recent research. They just push pills. Unfortunately, many snake oil salesmen have jumped on the supplement bandwagon and are promoting many unproven natural cures some of which may actually be very unhealthy. Do your research and don't believe everything you read. Another problem is that we all are different. What works for one person may not work for another.
George Cernigliaro
Given that this possible fix is quite specific in metabolic pathway, is there any way of knowing, a priori, how altering this pathway may effect other unwanted side effects? I'm sure it's too early to answer this. Also, as the article mentions, age-related cognitive decline seems to be auto-immune related; is this also a gut microbiome issue?
Signguy
It seems to me, if you exsersize, instead of being "dormant", eat a well balanced diet, stay away from doctors and their drug "fixes", and stay active, you should live well. Having good Genes helps too.
Still playing Racquetball at 71 and play with some in their 80's! (except for this Covid curse)
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