Study offers insight into how long-term inflammation may contribute to cognitive decline

Is your competent? doctor testing for this AND HAS EXACT PROTOCOLS TO STOP THE INFLAMMATION? NO? So, escaping responsibility and just blaming the stroke for your cognitive decline! I'd suggest screaming and talking to the president to get this person fired! 

 Study offers insight into how long-term inflammation may contribute to cognitive decline

The King's College London study, published in Nature Communications, offers insight into how long-term inflammation may contribute to cognitive decline in disorders such as Alzheimer's disease, aging, depression, and the lingering neurological effects of viral infections.

The scientists discovered that adding a molecule, that is involved in the inflammatory response, to stem cells from the hippocampus prevents the development of new neurons. The formation of new neurons in this region, known as hippocampal neurogenesis, is essential for learning, memory and mood regulation. It is one of the few parts of the human brain where new neurons are made in adults. Altered adult hippocampal neurogenesis is associated with aging, neurodegeneration, and mood disorders such as depression.

The study focused on cytokines, which are chemical signals that are released by the body in response to a threat, such as a viral infection. Cytokines ultimately act as triggers for the rest of the immune response, which helps the body fight the infection. High cytokine levels are also a hallmark of chronic inflammation.

Viral infection has previously been linked to changes in the ability to create new neurons in part of the hippocampus. However, how exactly infection and inflammatory cytokines affect creation of new neurons was previously unknown.

When researchers added one particular cytokine, called TNF‑α, to human hippocampal stem cells, it prevented them from developing into neurons. Instead, they switched into an "immune alert" state, releasing signals that can attract key immune cells, known as T cells, that drive inflammation, while simultaneously reducing the production of new nerve cells.

First author Dr Tinne A. D. Nissen, who completed the research as part of her PhD at King's College London, said: "What surprised us most was that the stem cells were not simply impaired by inflammation, they actively adopted behaviors that could potentially sustain immune responses in the brain."

Our findings reveal a new link between chronic inflammation and the brain's reduced ability to generate new neurons.

Inflammatory signals can effectively redirect hippocampal stem cells away from their normal role of producing neurons and toward supporting immune activity instead."

Professor Sandrine Thuret, co-corresponding author, Professor of Neuroscience, King's College London

The researchers also identified an unexpected signalling pathway behind this effect involving type I interferons, molecules typically associated with the body's antiviral defense. By blocking interferon signalling with an existing therapeutic antibody, some of the effects of inflammation were reversed – by restoring production of new neurons and preventing the attraction of T cells involved in the immune response.

Co-corresponding author Professor Linda S. Klavinskis, Professor of Viral Immunology, King's College London, added: "Our work uncovers a new mechanism that may help explain why ongoing inflammation is so damaging to brain health. Importantly, it also points to possible treatments to protect or restore the brain's regenerative capacity."

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This research was a collaboration between the Department of Infectious Diseases at the Faculty of Life Sciences & Medicine and the Department of Basic and Clinical Neuroscience at the Institute of Psychiatry, Psychology & Neuroscience, King's College London.

This research was funded by the Wellcome Trust as part of the "Neuro-Immune Interactions in Health & Disease Wellcome Trust PhD Programme, the Medical Research Council UK, a Medical Research Council Discovery Award, a PhD Studentship awarded by the Medical Research Council UK, The Galen and Hilary Weston Foundation, the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London.

Source:

King's College London

Journal reference:

Nissen, T. A. D., et al. (2026) TNF-α induces type I IFN signalling to suppress neurogenesis and recruit T cells. Nature Communications. DOI: 10.1038/s41467-026-74104-x. https://www.nature.com/articles/s41467-026-74104-x

Inflammation Forces Brain Stem Cells to Halt Neurogenesis

 How EXACTLY  will your competent? doctor prevent this inflammation? You need neurogenesis to recover according to your doctor; SO THERE BETTER BE A SOLUTION!

Inflammation Forces Brain Stem Cells to Halt Neurogenesis

Summary: A new study demonstrated that introducing inflammatory signaling molecules directly into human hippocampal stem cells brings new neuron production to a dead stop. Instead of simply dying or becoming damaged, the brain’s neural stem cells actively abandon their regenerative responsibilities, transforming into an “immune alert” state that actively fuels localized neuroinflammation.

Key Facts

• The Cytokine Intrusion: The team analyzed the behavior of cytokines, specialized chemical signaling proteins released by the body during immune threats, such as severe viral infections. While transient cytokine spikes help clear out acute sickness, sustained high levels are a classic hallmark of devastating chronic inflammation.
• The TNF-α Standstill: When researchers exposed human hippocampal stem cells to a specific pro-inflammatory cytokine called Tumor Necrosis Factor alpha (TNF-α), the cellular birth pipeline froze. The stem cells completely ceased differentiating into mature, functional neurons.
• The “Immune Alert” Takeover: To the shock of the investigators, the stem cells weren’t merely passive casualties of chemical stress. Instead, they actively assumed a hostile, immune-supportive behavior, pumping out high-alert chemical signals designed to recruit inflammatory T cells straight into the brain’s delicate learning centers.
  
• The Type I Interferon Accidental Route: By mapping the molecular cascade, the team identified a highly unexpected signaling pathway driving this cellular hijack: Type I Interferons. These molecules are traditionally recognized as the body’s first-line defensive shield against viral replication, but here they inadvertently act as the executioner of neurogenesis.
• Reversing the Damage: In a major therapeutic triumph, the KCL team introduced an existing therapeutic antibody designed to block Type I Interferon signaling. The intervention successfully reversed the damage, shutting down the recruitment of inflammatory T cells and completely restoring the stem cells’ capacity to regenerate fresh, healthy neurons.
• A Diagnostic Bridge for Long-Syndromes: This discovery provides an invaluable clinical explanation for the persistent cognitive impairments, “brain fog,” and mood disorders reported by patients recovering from aggressive viral infections, navigating major depressive disorders, or entering the early stages of Alzheimer’s disease.

Source: King’s College London

The King’s College London study, published in Nature Communications, offers insight into how long-term inflammation may contribute to cognitive decline in disorders such as Alzheimer’s disease, ageing, depression, and the lingering neurological effects of viral infections.

The scientists discovered that adding a molecule, that is involved in the inflammatory response, to stem cells from the hippocampus prevents the development of new neurons. The formation of new neurons in this region, known as hippocampal neurogenesis, is essential for learning, memory and mood regulation. It is one of the few parts of the human brain where new neurons are made in adults. Altered adult hippocampal neurogenesis is associated with ageing, neurodegeneration, and mood disorders such as depression.

What Happens To Your Immune System After One Sauna Session by mindbodygreen

 

I'm just got a personal sauna from NuRecover but will use a cold shower instead of a chiller bucket for the cold shock proteins. Still to be put together.

What Happens To Your Immune System After One Sauna Session

 There’s a reason sauna use keeps showing up in longevity research. Regular exposure has been associated with lower risks of cardiovascular disease¹ ,respiratory illness²,dementia³, and even overall mortality⁴ .But those outcomes don’t tell us much about the immediate effects. What actually changes in the body during a single session? And how quickly do those changes happen? A new study⁵set out to answer that by tracking immune responses before, during, and after a 30-minute sauna session, offering a closer look at the body’s short-term reaction to heat. 

What happens to your immune system during a 30-minute sauna

Researchers studied 51 adults, both men and women, during a standard Finnish sauna session set to about 73°C (roughly 163°F). Each participant spent 30 minutes in the sauna, with blood samples taken before, immediately after, and 30 minutes post-session. The goal was to track how immune cells and inflammatory signals changed in response to heat stress. Participants were allowed to drink water throughout, which helped control for dehydration and made the setup closer to a typical real-world sauna experience. Instead of just looking at overall immune activity, the researchers zoomed in on specific white blood cells and a wide range of cytokines, which are signaling molecules involved in inflammation and immune response. This gave a more detailed picture of how the body reacts in the short term. 

Sauna’s immediate effect on immune cells

The biggest shift came down to your white blood cells, which are a key part of your immune system. After the sauna session, those levels went up, including important types like neutrophils and lymphocytes. These are the cells that help your body spot and respond to anything that doesn’t belong, whether that’s a virus or another kind of threat. What stands out is how quickly this happens. The increase shows up right after the sauna, then goes back down within about 30 minutes. So this isn’t a long-lasting spike; it’s more like a short window where your immune system is a bit more alert. This pattern mirrors what happens during exercise. When you work out, immune cells move out of tissues and into your bloodstream, where they’re more ready to respond if needed. A sauna seems to trigger a comparable response, just through heat instead of movement. 

What about inflammation & body temperature?

One thing the researchers looked at closely was inflammation, since that’s often what people think of when they hear the body is under “stress.” But in this case, there weren’t big changes across most inflammatory markers. Out of dozens of signals they measured, only a few shifted in a meaningful way. That suggests your body isn’t going into a full inflammatory response during a sauna. Instead, the response seems more about mobilization than inflammation. Your immune cells are being redistributed and activated, not necessarily pushed into an inflammatory state. Body temperature did play a role, though. On average, people’s temperature rose by about 2°C (roughly 3.6°F) during the session. And the more it increased, the more certain immune-related signals shifted alongside it. 

Adding sauna use to your routine

 So what does this mean for your day-to-day routine? It doesn’t mean a single sauna session will prevent illness or replace other foundational habits. But it does suggest that sauna use can act as a short-term stimulus for your immune system, similar to a workout.If you already use a sauna, this adds another layer of context. That post-sauna feeling isn’t just relaxation. Your body is actively responding, mobilizing immune cells in a way that may support overall immune surveillance over time. 

If you’re considering adding it in, consistency matters more than intensity. This study looked at one session, but previous research has linked regular sauna use to broader health benefits, including a lower risk of certain chronic conditions.

It’s also worth paying attention to how you personally respond. Hydration, heat tolerance, and recovery all play a role in how beneficial the experience feels.

The takeaway

This study doesn’t suggest that sauna use is a cure-all. But it does offer a clearer picture of what’s happening in the body during a session. Your immune system isn’t passive in that environment. It’s responding, adapting, and briefly shifting into a more active state.

Art, peanuts and Dick Van Dyke: ageing well at Christmas

 I try to see lots of museums when I travel, next up.

Heading to Italy April 21-30 with Michigan Public Radio;3 nights at the Cardinal Hotel St. Peter in Rome;4 nights at Hotel Mary, Sorrento Coast; 1 night at Isola Sara Rome Airport Hotel.
Pompei and Naples here I come. The tiles in Pompeii probably qualify as original art

Art, peanuts and Dick Van Dyke: ageing well at Christmas

And all of a sudden – it’s almost Christmas! Another year of ageing well, for us all, we hope. The festive photo of Annabel and I above shows us flanking a Christmas tree decorated by our friend, artist Amy Robson. She handmade the dolls that decorate the tree. Making by hand, crafting in any form, is one of the greatest gifts we can give ourselves. Working with your hands lights up an extraordinary number of neural circuits at once: the combination of fine motor control, spatial feedback, decision making and flow builds cognitive reserve, protecting the brain long-term. 2026 will be the year I make something. Just not sure what yet. I’d gladly welcome your suggestions in the comments below.

The joy of art

Talking of art, if getting out and about to an art gallery is on your to-do list over the festive period, then you’ll also be reducing stress. Research by Kings College London, part-sponsored by the Art Fund, compared the physiological impact of viewing original artworks in a gallery, versus looking at reprints in a non-gallery setting.

Pro-inflammatory cytokines IL-6 and TNF-α, which are linked to stress and chronic disease,  dropped by 30% and 28% respectively for those viewing original art, with no change observed in the reproduction group. This suggests art has a potential calming effect on the body’s inflammatory responses.  I would also suggest that there’s something so uplifting about being in an art gallery – the light, the space, the calm – that must also lower stress, don’t you think?

A few other longevity-focussed stories which have crossed my desk this year, but not yet made it onto the blog:

Superagers

We know that there are an elite group of older people known as ‘superagers’: people 80 and up who have the same memory function as someone 20 to 30 years younger.  And we know that loneliness impacts cognitive function long term. So it’s not a huge surprise that superagers view social relationships as vitally important. A 25-year study by Northwestern University found this was the unifying factor among superagers – more so than diet, exercise regime or other lifestyle choices.

People with greater social connection(I have massive social connections.) experience less chronic stress, which elevates cortisol – which, in turn, leads to inflammation. That, in turn, could damage brain cells and even increase dementia risk.

The most super of agers

Talking of super-agers – or should that be supercalifragilisticexpialidocious-agers – the ineffable Dick Van Dyke turned 100 this month. He’s published a book detailing his 100 rules to living to 100. The headlines: he goes to the gym three times a week, dances, takes five lumps of sugar in his coffee, enjoys a power nap and sings every day. Sounds like a recipe for a good, long life (except, maybe, the sugar).

Peanuts

With Christmas, comes feasting, and all manner of treats. Don’t hold back from grabbing a handful of peanuts: research from The Netherlands published earlier this month linked two servings of them to improvements in both brain vascular function and verbal memory. The study focussed on skin-roasted peanuts – not the salted or dry-roasted kind – and found that eating two servings a day increased blood flow to the brain. Peanuts are rich in polyphenols and antioxidants. Berries and dark chocolate also contain these nutrients, so enjoy those this Christmas too.

Annabel on the radio

Annabel and I bonded over our love of books and reading, so it was a joy to hear her on BBC Radio 4’s  A Good Read, talking about one of her favourite books, The Living Mountain by Nan Shepherd. If you have access to BBC Sounds, you can listen there. Annabel’s episode was the last in the current series. And I can vouch that The Living Mountain is indeed a good read.

A bonus workshop on nutrition for better brain health

I’m running a bonus workshop to help you create Your 2026 Brain Food Plan on January 15th . It’s for everyone who has my course, Feed Your Brain Better. The course is digital so you can buy and access any time. It costs £37 – approx $49. The free bonus workshop is designed to help you stay consistent with nutrition for better brain health in 2026 – especially when things get busy – and will be on Zoom. Details of how to join the course – and the workshop – here

Christmas recipes from the archive

Of course, it wouldn’t be Christmas without some recipes from the Age Well archive. Here are a few of our festive favourites:

Christmas nuts

Griddled Brussel sprouts with parmesan

Spiced parsnip soup – warming and hearty

Vegetable tartlets for Christmas dinner  

Christmas granola

Beautiful-on-the-inside Christmas cake

Wishing you a very happy and healthy festive season

Susan

Targeting immune cells in the aged brain reveals that engineered cytokine IL-10 enhances neurogenesis and improves cognition

 We need both, do you have ANY CONFIDENCE AT ALL that your stroke medical 'professionals' will get human testing going?

Do you prefer your doctor, hospital and board of director's incompetence NOT KNOWING? OR NOT DOING? Your choice; let them be incompetent or demand action!

Targeting immune cells in the aged brain reveals that engineered cytokine IL-10 enhances neurogenesis and improves cognition

Author links open overlay panel, , , , , , , , , , , , , , , , , , , …

https://doi.org/10.1016/j.immuni.2026.01.016Get rights and content

Under a Creative Commons license

Open access

Highlights

• •
  The old brain contains exhausted T cells and unbalanced microglial inflammation
• •
  Delivery of engineered proteins into old mouse brains allows immune cell targeting
• •
  Checkpoint inhibition in old brains activates T cells and microglial inflammation
• •
  Engineered IL-10 restores microglial balance, neurogenesis, and cognition in old mice

Summary

The immune system could play an important role in the age-related decline in brain function, yet specific immune-based strategies to enhance brain resilience in older individuals are lacking. Here, we combined engineered proteins and direct brain delivery to target immune cell populations within the old brain. We detected T cells with an exhaustion signature in the old brain and targeted them with a potent engineered checkpoint inhibitor (RIPR-PD1). This led to T cell expansion and strong pro-inflammatory responses in many brain cell types, notably microglia. To rescue age-related inflammatory imbalances in microglia, we used the anti-inflammatory cytokine interleukin (IL)-10. IL-10 boosted anti-inflammatory responses in old microglia, but it also triggered pro-inflammatory signaling. An engineered IL-10 variant that uncouples pro- and anti-inflammatory responses positively impacted the transcriptome of multiple cell types, enhanced neurogenesis, and improved cognition in aged mice. Our findings pave the way for immunotherapies for the aged brain.

Graphical abstract

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Introduction

Brain function deteriorates with age. Additionally, age-related neurodegenerative diseases (e.g., Alzheimer’s disease and Parkinson’s disease) surge in the elderly population. While many pathways are remodeled in the brain during aging,1,2,3,4 a key feature of old brains is immune cell infiltration and inflammation. Aging leads to a pronounced increase in the number of T cells across several brain regions in mice and humans,5,6,7 including neural stem cell (NSC) niches8,9,10,11 and white matter tracts.12,13,14,15,16 T cells from old brains are clonally expanded,8,17 suggesting they have encountered antigens. T cell infiltration and clonal expansion are further accentuated in age-related neurodegenerative diseases.18,19,20,21,22,23,24,25,26 In parallel, pro-inflammatory pathways are strongly upregulated during aging in many cell types, and this is exacerbated in Alzheimer’s disease.8,13,27,28,29,30,31,32,33,34,35,36 A systematic understanding of age-related changes in brain immune cells may inform strategies to mitigate brain aging.

Could immune-based interventions be designed to counter brain aging? Modulating immune cells and inflammatory pathways can affect the old brain.12,13,28,30,37,38,39 But previous studies have relied on broad interventions, often performed in the periphery13 and in young or disease model mice.18,24,40,41,42,43,44,45 We lack strategies to target specific immune cell subsets and pathways within the old brain to determine their mode of action. Moreover, identifying such brain immune interventions could help develop “aging immunotherapies” and would be critical to counter aspects of brain aging and age-related brain diseases.

Here, we developed a platform that leverages engineered proteins and direct brain delivery to test immune cell-specific interventions in old mice. We identified T cells with an exhaustion signature and targeted them with a potent engineered checkpoint inhibitor, leading to T cell expansion and strong pro-inflammatory responses in many cell types, including microglia. To rescue age-related inflammatory balance in microglia, we used an engineered interleukin (IL)-10 variant that uncouples pro- and anti-inflammatory responses and found that it had beneficial effects on multiple cell types and cognition in aged mice. Our findings pave the way for novel immunotherapies for the aged brain.

Results

Characterization of immune cells in the aged brain

We systematically characterized immune cells in the aging brain, focusing on the subventricular zone (SVZ) neurogenic niche—a region that contains adult NSCs and declines during aging.46,47,48,49 Leveraging previously published single-cell RNA-sequencing (scRNA-seq) datasets,8,50 we found that SVZ neurogenic niches contained microglia (the brain-resident myeloid population), macrophages, CD8+ T cells, CD4+ T cells, and low numbers of other immune cells (Figures 1A and S1A). CD8+ T cells were not very numerous but significantly increased in number with age (Figure 1A, upper and middle panel). Microglia were the most abundant immune cell type and showed the largest age-related changes in gene expression (Figure 1A, lower panel). We thus focused on CD8+ T cells and microglia for further characterization and targeting in the old brain.

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Figure 1. Characterization of immune cells in the old brain

(A) Analysis of immune cell populations in the SVZ neurogenic niche of young (3–4 months, n = 7) and old (22–29 months, n = 6) male mice in two merged scRNA-seq published datasets.8,50 Top panel, quantification of the proportion of different immune cell types relative to the total number of cells. Data are mean ± SEM; each dot represents one mouse. Middle panel, age-dependent changes (log2[old/young]) in the abundance of each cell type. Bottom panel, age-dependent changes in gene expression per cell type. Dots represent differential expression MAST Z score for each gene. Genes significantly changed with age (Bonferroni-corrected p < 0.05) are in color.

(B) scRNA-seq analysis of CD8+ T cells freshly isolated from the brain and lung of old male mice (22–25 months, n = 11 mice, pooled). Uniform manifold approximation and projection (UMAP) clustering of all T cells colored by organ of origin, downsampled to 3,724 cells per organ. One independent experiment.

(C) UMAP as in (B) colored by cell type.

(D) Changes in the percentage of T cell subtypes in old brains vs. old lungs.

(E) Heatmap of top six marker genes for each T cell subtype in the old brain.

(F) FACS quantification of percent PD1+ and CD44+CD69+ of CD8+ T cells freshly isolated from the brains and lungs of old male mice (24 months, n = 6). One independent experiment.

(G) Heatmap of T cell marker genes in T cells from same dataset as (A).

(H) Left, representative images showing exhaustion scores for T cells in coronal brain sections of young (6 months) and old (28 months) male mice in a spatial transcriptomics (MERFISH) dataset.7 Right, quantification of exhaustion scores in T cells from young (3–6 months, n = 5) and old (26–34 months, n = 6) male mice across four brain regions, cortex (CTX), striatum and adjacent regions (STR), white matter tracts of the corpus callosum and anterior commissure (CC/ACO), and the ventricle (VEN). One coronal section per mouse. Boxplots of median and lower and upper quartile values.

(I) Left, representative immunofluorescence images of SVZ from young (4 months) and old (28 months) male mice. Red, CD8+ (T cells); green, PD1+ (checkpoint protein); blue, DAPI (nuclei). Scale bar, 10 μm. Right, number of CD8+ and CD8+ PD1+ T cells in the SVZ of young (3–4 months, n = 7) and old (28–32 months, n = 7) male mice. Each dot represents one mouse (average of two sections per mouse). One independent experiment.

(J) FACS quantification of the percentage of CD8+PD1+ and CD8+CD44+CD69+ T cells of live/CD45+ cells freshly isolated from the brain of young (6 months, n = 6) and old (24 months, n = 6) male mice. One independent experiment.

(K) Average changes in gene expression in microglia of the SVZ neurogenic niche of young and old male mice from three published scRNA-seq datasets.8,50,51 Red, upregulated; blue, downregulated genes.

(L) Heatmap of log-normalized counts for pro- and anti-inflammatory genes in microglia from the SVZ in a published dataset.8

(M) Log-normalized expression values of Socs3 (left) and combined genes in the IL-10 pathway in microglia from the SVZ in a published dataset.8 Horizontal lines, median.

(N) IL-10 signaling scores for microglia in spatial transcriptomics dataset.7

(O and P) FACS histograms and quantification of inflammation proteins in microglia (CD45+CD11b+) freshly isolated from the SVZ of young (3 months) and old (24 months) male mice (n = 6). Each dot represents one mouse (mean fluorescence intensity [MFI] values from ∼500 microglia per mouse). One independent experiment.

Data are mean ± SEM. p values, two-sided Wilcoxon rank-sum test. NS, not significant.

See also Figure S1.

More at link.