Like an ageing security system, the body’s defences falter over time, leaving gaps for illness to sneak in. New science explores why our inner guards grow inattentive and, potentially, how we can bolster their focus.
New research finds that as we age, T cells responsible for “remembering” past pathogen threats decline as the thymus gland produces fewer naive T cells to combat new bugs. An imbalance also emerges between CD4+ “intelligence gathering” cells and overzealous CD8+ “first responder” cells. This partly stems from ageing T cells paying less heed to proteins like TRIB2, which typically restrain CD8+ cells. It resembles a classroom where the teacher loses control and rambunctious students run amok.
But solutions exist to make our aged inner force sharper. Research on specially formulated vaccines, immune-boosting skin injections, compounds targeting T cell pathways, and viral vectors carrying relevant antigens is showing promising results for amplifying immune reactions. As we better understand how ageing impacts cellular energetics and DNA protection, more immunoregulatory targets may emerge.
Here is how immunity in older adults degrade over time — and the many ways researchers are exploring to keep it sharp even during our golden years.
Shedding memory
A key reason why immunity in older adults can grow weaker with age is that over time, the body sheds “memory” T cells that recognize past pathogens – a direct result of the thymus producing fewer ‘new’ T cells.Our bodies rely on new cells to combat new threats, in much the same way that antivirus programs need regular updates to combat newer computer viruses.
The growing imbalance of immune cells with age is not just about losing memory. Imbalances also emerge where CD8+ “rapid responder” T cells become overactive compared to intelligence gathering CD4+ cells. This results somewhat from ageing cells paying less attention to proteins like TRIB2 that normally restrain overzealous CD8+ activity.
The need to update vaccine regimens
Understanding how immunity in older adults degrade over time is the first step towards finding a fix. To safeguard the vulnerable, researchers are rethinking everything from vaccine boosters to the very molecules that control T-cell behavior.
The CDC recommends vaccination schedules for older adults, such as the Shingrix vaccine for those aged 50 and older and pneumococcal vaccination for those aged 65 and older. However, a study revealed concerns about the durability of the current diphtheria vaccination strategy. A significant number of participants experienced a decline in protection against diphtheria, suggesting the need for exploring alternative approaches to improve responses, such as strengthening T-cell responses or using alternative adjuvants.
Dr Claudio de Lucia, geriatrician at ASL Napoli 1 Centro in Italy, underscores the benefits of seasonal influenza vaccination for the elderly. “Due to age-related immune system alterations, specialised high-dose and adjuvanted inactivated influenza vaccines have been tailored for older populations.”
While vaccines remain important in safeguarding public health, their efficacy declines with age. Certain vaccines confer lifelong protection, whereas others offer only short-term immunity. For instance, “vaccination against infections like yellow fever may provide lifelong immunity, while vaccines like varicella zoster virus lose their effectiveness in older adults within eight years,” says Dr Abhinav Saurabh, a postdoc researcher at the United States’ National Institutes of Health,highlighting the transient nature of immunity in older adults, even with vaccinations.
Strategies to enhance vaccine response
Researchers are looking into targeted compounds, immunotherapies, and genetic techniques to enhance the immune system’s efficacy in older adults. Specific drug molecules target internal pathways, significantly boosting T-cell behaviour critical for disease defence. In trials with older adults (65+), these drugs notably amplified immune responses to flu vaccines. In phase 2 trials, an oral variant of these drugs amplified the expression of antiviral genes and reduced respiratory infections in this age group.
Another avenue of research revolves around booster doses to enhance vaccine responses in older adults. Administering booster doses every decade, and combining vaccines like tetanus, diphtheria, pertussis, and polio, has shown enhanced immune responses compared to young adults receiving single doses.
Furthermore, adjuvants—components intensifying vaccine efficiency—utilise a blend of squalene with oil and water, fostering an environment that elevates immune responses.
Going skin-deep
Administering a vaccine under the skin, rather than injecting one in to a muscle, has been shown to yield a stronger immune response for certain vaccines. For instance, using the skin for the flu vaccine resulted in a significantly enhanced immune response compared to intramuscular injection.
Viruses can also be useful vehicles for vaccines. Vector-based vaccines like MVA (Modified Vaccinia virus Ankara), have received attention for older adults’ immunisation. These vaccines, utilising viruses as carriers, deliver specific antigens, prompting the immune system to identify them as foreign entities and produce an immune response.
Vaccines that eliminate the very genes that compromise immune responses are also being researched and developed.
Understanding how T cells function is like having a recipe for developing superior vaccines for older individuals. As scientists work to enhance the immune systems of older people, understanding T-cell behaviour is crucial. This aids in better management of our health, especially as we age.
“Thymic involution affects pathogen detection by reducing the number of new T cell generations, leading to decreased diversity in the peripheral T cell pool,” adds Dr Saurabh.
Understanding how ageing affects not only the immune system but also brings about significant shifts in metabolic functions and cellular health is essential. Ageing impacts the role of mitochondria, the energy generators of cells, making them less efficient and increasing the risk of age-related diseases.
Another age-related change involves the enzyme telomerase, crucial for maintaining the length of telomeres—protective caps at the ends of chromosomes. As we age, telomerase activity decreases, leading to DNA damage in T cells. This damage makes T cells resistant to normal cell death, potentially contributing to age-related diseases.
Understanding ageing provides hope for enhanced immunity in older adults. Dr Lucia emphasised that to boost immunisation potential, “The immune system can be influenced by particular compounds, dietary supplements, probiotics, or nutraceuticals, especially recommended for frail older individuals, potentially leading to positive effects on vaccination outcomes.”
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