LongeCityNews Last Updated: 11 April 2026 - 12:19 AM

In the US alone, new strains of influenza reliably emerge to kill tens of thousands of older people every year, hundreds of thousands in a bad year. The research and development community has yet to fully develop and deploy any of the possible approaches that might effectively shut down viral infections, such as descendants of the DRACO technology, and the aged immune system becomes ever less able to resist and control infections of all sorts. In later life, the immune system also becomes more inflammatory, more vulnerable to runaway inflammation during infection that leads to sepsis. Further, other aspects of aging make organs and tissues less able to resist the stresses that result from severe infection and accompanying inflammation.

One of the ways in which influenza infection and accompanying inflammation kills older people is by provoking what is known as a major adverse cardiovascular event, meaning a heart attack or stroke, that would otherwise not have occurred. One of the ways that influenza vaccination can help to reduce mortality is by preventing evident infection and all of its consequences. Another, as shown in today's open access paper, is by reducing the severity of the infection, the stress placed upon organ systems, and thus the risk of fatal heart attack and stroke. There are many good reasons to maintain a vaccination schedule in late life, even given the reduced capacity of the aged immune system, and this is one of them.

Influenza vaccination attenuates acute myocardial infarction and stroke risk following influenza infection: a register-based, self-controlled case series study, Denmark, 2014 to 2025

Influenza infection can trigger acute cardiovascular events through short-lived systemic inflammation that favours a pro-thrombotic state and destabilises vulnerable atherosclerotic plaques. Self-controlled case series studies, which compare event rates within individuals during prespecified risk time windows against their own baseline time, have consistently shown transient increases in cardiovascular risk after laboratory-confirmed influenza. A Canadian study reported a sixfold increase in acute myocardial infarction risk during the first 7 days after positive test results (incidence rate ratio (IRR) = 6.05); estimates from Spain and the Netherlands are similar. Studies employing finer temporal resolution have further characterised the risk profile, indicating that peak incidence increases within 3 days, then tapers back within 2-4 weeks.

Among mounting evidence suggesting that influenza vaccination reduces cardiovascular risk, a recent meta-analysis of randomised controlled trials estimated 32% lower risk. Two successive self-controlled case-series studies in the United Kingdom demonstrated a 20-23% reduced incidence for both acute myocardial infarction and stroke. In particular, the second study reported no evidence of sex-specific differences, and effects were slightly stronger among people vaccinated early in the influenza season. A meta-analysis including these same two studies provided further evidence of the protective effect of vaccination (pooled IRR = 0.84 for acute myocardial infarction).

In this self-controlled case series study in Denmark spanning 2014 to 2025, PCR-confirmed influenza was followed by a sharp, transient rise in the first-ever hospitalisations for acute myocardial infarction and stroke. Risk concentrated in the first week, peaking within 3 days, and declined back to baseline by 2 weeks. Prior influenza vaccination was associated with a significantly lower excess risk. This temporal profile aligns with studied mechanisms. Influenza infection has been shown to precipitate atherogenesis and has been epidemiologically linked to acute myocardial infarction and stroke in adults 40 years and older.

Vaccination can plausibly mitigate these effects by priming adaptive immunity and reducing viral replication, thereby dampening systemic inflammatory peaks. By vaccination status, the adjusted IRRs for cardiovascular events in this study were 4.7 and 2.4 for unvaccinated and vaccinated episodes, respectively. To our knowledge, this is the first study to show statistically significant attenuation of post-influenza cardiovascular risk by vaccination. A Canadian study observed similar results but possibly lacked statistical power to confirm them.

A new study shows that the overexpression of somatostatin (SST), a neuropeptide produced in neurons and acting mostly on microglia, lowers inflammation and amyloid β burden, improving cognitive abilities in a mouse model of Alzheimer’s. Drugs affecting this pathway are already available [1].

The unusual suspect

In Alzheimer’s disease, many signaling pathways in the brain become dysregulated. Since going after the main hallmarks of the disease (amyloid β and tau protein accumulation) has only yielded modest results so far, scientists are exploring various secondary targets whose levels correlate with the disease.

One such molecule is SST, a small signaling protein (a neuropeptide) released by a specific class of inhibitory neurons in the brain, which help regulate brain activity, mostly by calming it. SST binds to a family of five receptors called somatostatin receptors (SSTR1-5), and those are preferentially expressed by microglia, the brain’s resident immune cells. Microglia hyperactivation leads to chronic inflammatory states and has been linked to Alzheimer’s and other dementias [2].

Importantly, SST levels are lower in Alzheimer’s patients than in healthy people [3]. However, whether SST actually talks to microglia directly and whether the loss of SST in AD could be making microglial activation worse had never been systematically tested.

In a new study from Daegu Gyeongbuk Institute of Science and Technology in South Korea, published in Brain, Behavior, and Immunity, the authors hypothesized that SST normally keeps microglia in a healthier, more controlled state, and that its loss in Alzheimer’s contributes to the harmful microglial hyperactivation seen in the disease. They tested their idea first in isolated cells, and then in living mice.

Reduced microglial activation and inflammation

First, the researchers grew separate cultures of neurons, astrocytes (supportive brain cells), and microglia, and confirmed that microglia indeed express SSTR2, but not SST, which was expressed exclusively in neurons. Essentially, neurons have the key, and microglia have the lock.

They then treated primary microglia, isolated directly from mouse brains, with SST at various doses and time periods. Measurements of phagocytosis, the process when cells engulf and digest particles and the primary mechanism by which microglia clear amyloid β and debris, found that SST treatment indeed boosted phagocytosis in a dose-dependent manner, while blocking SST abolished the effect.

The researchers then treated microglia with SST for 48 hours and measured mRNA levels of a panel of signaling proteins that coordinate inflammatory responses (cytokines). They found that the treatment dampened the levels of the pro-inflammatory cytokine IL-12 and, conversely, elevated the levels of TGF-β1, a broadly immunosuppressive and tissue-remodeling cytokine associated with microglial homeostasis. Together, these shifts suggest that SST nudges microglia toward a less inflammatory state, hinting at a neuroprotective effect. However, the effect sizes were modest, and several cytokines tested showed no significant change.

What would happen to microglia if we manipulated SST levels in living animals? The researchers delivered an SST overexpression gene into the dentate gyrus neurons, the hippocampal region associated with memory and learning and heavily affected in Alzheimer’s, of healthy mice. Overexpressing SST did not affect microglial morphology and function, as the mice’s microglia were also mostly healthy and stayed that way following the treatment. Still, the treatment reduced markers of microglia activation. Conversely, knocking down endogenous SST led to microglia acquiring activation-associated morphology.

The team then moved to a mouse model of Alzheimer’s: 5xFAD, which shows extremely rapid Aβ plaque accumulation. The authors first confirmed that microglial activation in these mice is age-dependent and becomes pronounced around 5 months.

Overall microglial density was significantly reduced in SST-overexpressing 5xFAD mice compared to controls (a good sign), and microglial morphology was partially preserved. PCR analysis showed reversal of several activation-associated markers. Importantly, even at this early stage of the disease, there were positive signs with regard to Aβ accumulation, but overall plaque burden was not one of them.

Cognitive benefits in vivo

Two weeks after injection, the mice underwent a battery of cognitive and behavioral tests. Anxiety and recognition memory were unaffected, but SST-overexpressing 5xFAD mice eventually started showing significant improvements in spatial memory.

Finally, the researchers repeated the overexpression experiment in 10-month-old 5xFAD mice – a late-disease timepoint with extensive, well-established plaque burden. At this point, two weeks of SST overexpression clearly reduced microglial activation, Aβ plaque density, and average plaque size. This suggests that SST’s effects on overall plaque burden become evident when plaques are more established.

Importantly, approved drugs targeting SST receptors already exist, such as for treating acromegaly. This raises the possibility of repurposing them to treat Alzheimer’s patients, who currently have very few options.

Professor Jiwon Um from the Center for Synapse Diversity and Specificity at DGIST, the study’s lead author, said: “This study demonstrates for the first time that somatostatin, a brain neurotransmitter, can directly regulate the state of immune cells to alleviate dementia pathology and improve memory function. Previous clinical trials for dementia faced significant limitations. However, drugs already approved and used to treat other conditions now show new potential for application in treating dementia and neuroinflammation based on this newly discovered mechanism.”

Literature

[1] Jung, H., Hyun, G., Kim, S., Jeon, Y., Han, K. A., Lee, K. J., … & Um, J. W. (2026). Somatostatin-induced modulation of microglial activity contributes to mitigating Alzheimer’s disease pathology. Brain, Behavior, and Immunity, 106563.

[2] Lue, L. F., Kuo, Y. M., Beach, T., & Walker, D. G. (2010). Microglia activation and anti-inflammatory regulation in Alzheimer’s disease. Molecular neurobiology, 41(2), 115-128.

[3] Davis, K. L., Davidson, M., Yang, R. K., Davis, B. M., Siever, L. J., Mohs, R. C., … & Targum, S. D. (1988). CSF somatostatin in Alzheimer’s disease, depressed patients, and control subjects. Biological psychiatry.

Researchers here describe a novel approach to encourage greater regeneration in heart tissue following the injury and lost function incurred during a heart attack. Their work falls into the growing category of practical gene therapies in which a small amount of easily accessible tissue, such as fat or muscle, is transfected to form a factory that generates and releases a beneficial circulating protein. Only a low dose of gene therapy vector is needed, and all of the present challenges in broader delivery of gene therapy are bypassed. The scope of possible uses is restricted to situations in which benefits can be derived from increased amounts of a specific protein in circulation, but this is still a large enough set of possibilities to support a broad industry.

During the first days of life, many mammals have a short-lived ability to regenerate heart muscle cells. A hormone called atrial natriuretic peptide (ANP) plays a key role by encouraging the growth of new blood vessels, calming inflammation, and reducing the formation of scars. As an individual ages, the amount of ANP in their bodies decreases substantially, and the regenerative capacity observed in newborn hearts largely disappears by adulthood. Researchers have understood the potential of ANP for decades, but it's difficult to use as a conventional drug because it begins breaking down after just a few minutes in the body.

Delivering a drug to the heart in a sustained and minimally invasive way is a significant challenge. Drugs aimed at organs such as the liver, lungs, or spleen can often accumulate naturally because of the unique features of their vascular systems and cellular uptake mechanisms. By contrast, the heart lacks such natural accumulation mechanisms, making efficient cardiac drug delivery more difficult. For researchers the solution was to stop trying to deliver the drug to the heart at all. Instead, they developed a two-phase approach that starts by creating a "prodrug" in skeletal muscle before transforming it into ANP within the heart itself.

The researchers designed RNA-lipid nanoparticles that encode Nppa, causing muscle cells in the thigh or arm to produce a molecule called pro-ANP. This molecule, which is not reactive in the body, circulates through the entire bloodstream. A specific enzyme, called Corin, transforms it into ANP. Corin is roughly 60 times more common in the heart than in other organs. In other words, the drug circulates until it reaches the one organ equipped to activate it. In lab experiments, a single injection significantly reduced scarring and improved heart function in small and large animals.

Link: https://www.engineering.columbia.edu/about/news/new-rna-therapy-could-help-heart-repair-itself

Researchers here review the landscape of immune aging with a particular focus on vulnerability to respiratory infections, such as influenza. As we age the immune system becomes ever less capable, the outcome of impaired manufacture of new immune cells, as well as issues that affect the internal workings of cells throughout the body, such as mitochondrial dysfunction and cellular senescence. At the same time the immune system becomes ever more active and inflammatory, a maladaptive reaction to forms of damage in cells and tissues. This creates a landscape in which infectious pathogens find it easier to overwhelm immune defenses, and in which inflammatory reactions to infection can readily become life-threatening, amplified by a dysfunctional immune system.

Every country around the globe is facing continuous growth in both the size and the proportion of older people; by 2050, the global population aged 60 years and above is projected to double, reaching approximately 2.1 billion people. As the population shifts towards older ages, new challenges are emerging, including increased healthcare demands. Among these challenges is "the destruction and remodelling of immune organ structure as well as innate and adaptive immune dysfunction with ageing", so-called immunosenescence, alongside inflammageing, a characteristic inflammatory state in which high levels of pro-inflammatory molecules are expressed. Both states predispose older adults to dysregulated immune responses and, inadvertently, to increased proportions of adverse outcomes, especially in the context of infections such as respiratory viral infections.

In this review, we examine the molecular and cellular pathophysiological mechanisms of immunosenescence and inflammageing that predispose older adults to increased morbidity and mortality from respiratory viral infections. We also outline the clinical implications of the ageing immune system, along with the most up-to-date evidence on possible biomarkers, preventative measures and treatment options aimed at mitigating the effects of immunosenescence on the vulnerability of older adults in respiratory viral infections.

Link: https://doi.org/10.1183/16000617.0248-2025