How Hidden Infections May Be Quietly Accelerating Human Ageing
New research uncovers how lifelong microbes reshape immunity, metabolism, and the brain.
For decades, scientists studying ageing have largely focused on internal wear-and-tear: cellular senescence, DNA damage, and epigenetic drift. These biological processes—measured today through popular “biological age” tests—are often assumed to happen in a sterile, microbe-free body. But what if a major driver of ageing has been hiding in plain sight?
A new review by researchers Amy D. Proal and Michael B. VanElzakker argues that persistent and chronic infections may be one of the most overlooked contributors to human ageing. From herpesviruses to intracellular bacteria and parasites, many microbes quietly persist in tissues and nerves for decades, subtly distorting cellular signaling, metabolism, and immune function. The authors propose that pathogens can accelerate nearly every hallmark of ageing—and may even help initiate neurodegenerative diseases like Alzheimer’s.
A Lifetime of Microbial Hitchhikers
Humans acquire microbes throughout life—viruses, bacteria, fungi, and parasites. Some infections occur before birth, others in childhood, and still more through adulthood. Many of these pathogens never fully disappear.
- Over 90% of people carry at least one herpesvirus, capable of long-term latency.
- Up to 50% of people globally carry the parasite Toxoplasma gondii.
- Persistent SARS-CoV-2 RNA has been detected in tissues months after infection.
These organisms don’t simply sit idle. Even when “latent,” they express proteins that can alter human gene expression, mitochondrial function, and immune signaling.
How Pathogens Mimic and Hijack Ageing Pathways
1. Inflammaging: Slow-Burn Inflammation
Chronic low-grade inflammation—known as inflammaging—is a hallmark of getting older. Persistent pathogens directly fuel this process. Viral proteins and bacterial components like LPS continuously activate immune pathways.
In animal studies, ageing magnifies the impact of infection: an E. coli infection caused far more cognitive dysfunction in older rats than in young ones due to “primed” microglia.
2. Cellular Senescence: Pathogens Push Cells Into Permanent Arrest
Several microbes can directly induce senescence.
- Salmonella Typhi produces a toxin that damages mitochondrial DNA, triggering senescence-related inflammation.
- Senescent cells become easier for viruses like influenza or varicella-zoster to infect—creating a harmful loop.
3. Mitochondrial Hijacking and the Warburg Shift
Viruses and intracellular bacteria rely on host metabolism for replication. To fuel their growth, they reprogram cells into a Warburg-like state, favoring glycolysis over normal mitochondrial respiration.
- Cytomegalovirus increases glucose consumption and lactate production.
- Borrelia burgdorferi (Lyme disease bacteria) pushes immune cells into glycolysis through the mTOR pathway.
Over decades, such metabolic rewiring can resemble age-associated mitochondrial dysfunction.
4. Protein Mimicry and Signaling Distortion
Many pathogens produce proteins that closely mimic human molecules.
A striking example: viruses from the Iridoviridae family produce insulin-like peptides that bind human insulin receptors, altering metabolism.
A massive analysis found 122 viruses interacting with 69 human proteins linked to longevity pathways, including mTOR—one of the most important regulators of ageing.
5. Telomere and Epigenetic Damage
Some pathogens directly affect telomeres and epigenetic patterns:
- HHV-6 can integrate into telomeres, shortening them.
- COVID-19 survivors showed accelerated epigenetic ageing by ~10 years on average and significant telomere shortening.
- Cytomegalovirus seropositivity correlates with faster epigenetic ageing.
Ageing Brains, Hidden Microbes
The review highlights mounting evidence that infections may contribute to diseases such as Alzheimer’s and Parkinson’s.
- A Swedish registry study found that infections treated over 10 years before diagnosis increased the risk of Alzheimer’s and Parkinson’s.
- COVID-19 boosted the 1-year risk of Alzheimer’s by 1.69-fold in older adults.
- In Alzheimer’s brain tissue, researchers have identified viral proteins, fungal markers, and oral bacteria toxins, often near amyloid plaques.
Compellingly, amyloid-β—long considered pathological—acts as an antimicrobial peptide, trapping viruses like HSV-1 or HHV-6. This suggests amyloid plaques may form because of infection, not merely ageing.
Therapies That Slow Ageing May Work by Controlling Infection
Some popular longevity interventions appear to reduce pathogen activity:
- Rapamycin, an mTOR inhibitor, improves immunity and reduces infections in older adults; it also slows some viral replication.
- Metformin activates AMPK, depriving viruses of energy and reducing oxidative stress needed for viral replication.
- Glutathione disrupts bacterial biofilms and reduces viral ROS signalling.
- NAD+ boosters enhance antiviral gene expression.
- Herpes antivirals have been linked to an ~90% reduction in dementia risk among infected individuals.
This perspective reframes longevity medicine: treating persistent infections may extend healthspan.
The Missing Tools: We Can’t Yet Measure These Microbes Well
A major barrier is diagnostic. Most chronic infections hide in tissues, not blood, making them difficult to detect. New tools—ultrasensitive protein assays, cell-free RNA metagenomics, immune-repertoire profiling—may eventually allow clinicians to track persistent pathogens just as they track cholesterol.
A New Paradigm for Understanding Ageing
The authors argue that ageing cannot be fully understood without incorporating infection into the model. Persistent pathogens interact with metabolism, immunity, and gene regulation in ways that mirror—and may drive—the hallmarks of ageing.
If this paradigm is correct, addressing hidden infections could become as essential to healthy ageing as diet, exercise, and genetics.
The study is published in the journal Ageing Research Reviews . It was led by Amy D. Proal from PolyBio Research Foundation, USA.
