In just over five years I will turn 60, which is a daunting prospect. I already have one age-related disease – hypertension – and, given the odds, will be lucky not to have been diagnosed with at least one more by then. After that, age-related conditions are likely to pile up until the inevitable end. It will be a similar story, no doubt, for many of you. We are living longer than before, but those extra years aren’t necessarily healthy ones.
Yet if recent developments are anything to go by, my sons may be luckier. Rather than face a laundry list of common ailments in their 70s and 80s, they may be able to immunise themselves against them. They could celebrate middle age with a vaccination that will make them immune to Alzheimer’s, cancer or hypertension. They might even get an anti-ageing panacea that will vaccinate them against all of the above and more, helping them face their later years in a healthier state than most of us can hope for today.
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In the battle against the diseases of old age, an age-old medical technology suddenly looks like a game changer. Vaccines, the injections that we most commonly associate with infectious diseases such as covid-19 and measles, are now showing promise in treating non-infectious diseases – particularly those associated with advancing years. So rapidly is this field progressing that, given a fair wind, there are hints that I – and others my age – may even benefit from some of these vaccinations ourselves. It sounds too good to be true, but vaccinating against the worst aspects of ageing is looking more like a question of when, not if.
The first successful vaccine was for smallpox, invented in 1796 by Edward Jenner. Such jabs now exist for most infectious diseases and are arguably one of the most effective medical interventions to date. A found that, since 1974, vaccines have averted 154 million deaths worldwide, including 146 million among children under 5.
The rationale of vaccination is to present the immune system with small chunks – called antigens – of an infectious organism to provoke an immune response and lay down an immune memory so that subsequent contact with the real pathogen is quickly dealt with.
It is fairly easy to elicit a useful response from the immune system in reaction to an infectious agent because the body recognises it as being “non-self”. Non-infectious diseases, on the other hand, arise from a person’s own cells, which makes it more challenging to spark such a response – but not impossible.
Cancer vaccine
The first non-infectious disease to be targeted by vaccination was cancer. In the early 1980s, a team at Johns Hopkins University in Maryland injected 20 people who had colorectal cancer mixed with the BCG vaccine, originally developed against tuberculosis but known to also be a general immune-system stimulator. The idea was to raise an immune response to the participants’ own tumours.
Just over two years later and all 20 were still alive, whereas four of the 20 people in a control group had died, a statistically significant difference. Other trials using the same technique found .
Cancer vaccines are different from traditional vaccines: they are therapeutic rather than prophylactic. But they still qualify as vaccines. “A vaccine is anything that stimulates the immune system in a way that benefits the host,” says at Harvard Medical School, who is working on their use as treatments, including for Alzheimer’s disease.
Progress on cancer vaccines has been slow, though. Cancer cells are exceptional at hiding from the immune system, not least because they are cells that originate from the person’s own body. So far, there have been more than 600 clinical trials for cancer vaccines. As yet, however, only one has made the grade and its impact has been moderate. Provenge for prostate cancer was approved in the US in 2010 but hasn’t set the world on fire, according to at Harvard University. It is relatively expensive, has only a modest benefit and .
But hope springs eternal. Many cancer cells turn out to be studded with antigens not normally present in the human body. These “neoantigens” often arise through genetic mutations within the cancer cell and can present a juicy target for the immune system. The discovery of neoantigens has helped to rejuvenate the field, says at Icahn School of Medicine at Mount Sinai in New York. A recent human trial using a molecule called mRNA to stimulate the production of neoantigens to the immune system, for example.
The stuttering progress of this approach for cancer hasn’t dampened the belief that non-infectious diseases can be targeted by vaccination. Many age-related conditions, in particular, are characterised by the excessive accumulation of specific proteins, which can be exploited by vaccines to evoke an immune response.
Alzheimer’s disease, for instance, has long been associated with the build-up of certain forms of two proteins, beta-amyloid and tau, in and around brain cells. The exact role these play in the disease is controversial, but they remain two of the strongest candidates we have as causative agents.
Vaccines are in development against both, and they are badly needed. This debilitating and ultimately fatal condition is the most common form of dementia. In 2023, an estimated , and that number could grow to 13.8 million by 2060 without a swift medical breakthrough. Current treatments are extremely limited.
Alzheimer’s vaccines
According to at the Chinese Academy of Sciences in Beijing, there are six ongoing clinical trials of vaccines against beta-amyloid or tau. The idea behind them is fairly straightforward: the vaccine contains an active ingredient designed to stimulate the immune system to produce antibodies against the proteins. The antibodies cross the blood-brain barrier, bind to the proteins and trigger white blood cells to clear them out in the hope that this slows the progression of the disease.
But there was a challenge: both beta-amyloid and tau are normal proteins expressed in the brain, and hence tolerated by the immune system. However, in their pathogenic form, these proteins are misfolded. This difference presented a novel target, says Liu. The trick is to turbocharge the natural immune response to these misfolded versions of the proteins with vaccine additives called adjuvants, which alert the immune system to danger.
Swiss biopharmaceutical company AC Immune has doing just this in early-stage human trials, one against . The ultimate goal, says company spokesperson Gary Waanders, is to vaccinate people at the very earliest stages of Alzheimer’s to slow or halt disease progression. That may mean people who have yet to develop any symptoms at all. A recently developed blood test can spot the stirrings of tau-related pathology before any cognitive deterioration appears. “The vaccines will ultimately be given not only to treat Alzheimer’s, but to help prevent it,” says Weiner.
My hope while researching this article was that my sons may have the opportunity to try such vaccines, but Waanders hints that I might also be in with a chance of receiving it. He says that AC Immune’s beta-amyloid vaccine might make it on the market as soon as 2029 if everything goes smoothly.
Meanwhile, the US Food and Drug Administration recently granted another amyloid-busting vaccine – in Cape Canaveral, Florida – a fast-track designation, so that it can be expedited through its review process. It has shown promise in human trials, says Vaxxinity CEO , with 98 per cent of people responding to the vaccine. “They developed antibodies. These antibodies crossed the blood-brain barrier. They engaged the target. We slowed cognitive decline by about 50 per cent.” UB-311 is currently on track for a larger trial that will include around 3000 people.
There are other ways of leveraging the immune system to clear out beta-amyloid. Scientists at the Ann Romney Center for Neurologic Diseases in Boston, Massachusetts, led by Weiner, are testing a vaccine that is in the neck and from there send immune cells called monocytes into the brain. “The monocytes go and clear amyloid,” says Weiner. The vaccine has been shown to remove beta-amyloid in mouse models of Alzheimer’s and is heading into early human trials.
Which anti-ageing methods actually work?
Clearly, there is no guarantee that any of these Alzheimer’s vaccines will make it into use. Numerous experimental ones have already fallen by the wayside, either due to lack of efficacy or adverse reactions.
Regardless, hopes remain high that these obstacles can be overcome. “One day, we will be treating and preventing Alzheimer’s with vaccines,” says Weiner. “Of course, it doesn’t happen overnight. But we’re doing it.”
Something else my sons may be interested in following is the progress of vaccines for vascular system diseases. Like hundreds of millions of others around the world, I have hypertension, or high blood pressure, and, as it tends to run in families, they are both at higher risk of developing it too.
Current first-choice therapies – drugs known as calcium-channel blockers and ACE inhibitors that prevent blood vessel narrowing – are effective, but don’t tackle the root cause, according to at Huazhong University of Science and Technology in Wuhan, China.
The primary regulator of blood pressure is a receptor in the arteries. When activated, it causes blood vessels to constrict and blood pressure to rise. The receptor can be deactivated with drugs called alpha-1 blockers, but they lack specificity and have a short lifetime in the blood, so they aren’t prescribed as front-line drugs. To solve this problem, in 2019, Liao and colleagues that elicited antibodies that blocked the arterial receptor in mice, with promising results.
The upshot is that there is solid progress with single-target vaccines of this sort, and the list of potential conditions of older age that could be treated this way goes on. There are versions in trials that attempt to fight , and even . But while vaccines for individual conditions are indeed a welcome addition to our armoury, there is one more vaccine candidate that I have been following particularly closely.
Cell senescence
It is a general-purpose anti-ageing vaccine and its target is senescent cells. These cells have suffered some sort of irreparable damage and stopped dividing, but they don’t die. They are usually cleared out by the immune system, but this process falters with age and senescent cells build up in tissues, secreting a potent cocktail of inflammatory molecules in a vain attempt to summon an executioner. Left unchecked, these secretions are highly toxic, damaging surrounding tissues and leaching into the bloodstream. Recent research suggests that a build up of senescent cells is a contributing cause of several diseases of older age.
Numerous drugs that appear able to destroy senescent cells are already being tested and have shown early promise in more than 40 different age-related diseases, according to at the Mayo Clinic in Rochester, Minnesota. Multiple , but, as yet, only two have reached the stage at which a large number of people have been given the drug or a placebo to test effectiveness and, according to at pharmaceutical company StarkAge Therapeutics in Lille, France, their benefits have thus far proved limited. The classical drug approach has “probably reached its limits in term of clinical development”, he says.
A big problem is that most of these “senolytic compounds” work by reversing senescent cells’ steely refusal to activate a self-destruct mechanism called apoptosis. But the drugs can also push healthy cells down the same pathway, which raises the possibility that they will damage non-target tissues.
That is where vaccines come in. Senescent cells commonly express very high levels of antigens that are absent or scarce in non-senescent cells. These “seno-antigens” are a cry for help to the immune system, which rounds up troops to dispose of them. The belief is that vaccines that target seno-antigens can help boost the immune system’s response, destroying senescent cells while leaving healthy ones alone.
The end of ageing?
In 2020, a team led by at Osaka University Graduate School of Medicine in Japan created a , which is present on the senescent cells that accumulate in the visceral fat that is found on and around organs. Mice given the vaccine, then fed an obesity-inducing diet, had much lower levels of these senescent cells than regular obese mice and had improved glucose metabolism and reduced insulin resistance. This seminal study not only shows that senescent cells can be eliminated by vaccination, but also that this improves important physiological functions, says Liu.
A year later, a team led by at Juntendo University Graduate School of Medicine in Tokyo, Japan, did something similar. This time, the work involved aged mice and senescent cells in the lining of their blood vessels, which are a known risk factor for atherosclerosis, the process by which arteries narrow and stiffen. The vaccinated mice had a – a measure of how long they remained in good health – and a longer lifespan than those that received a placebo.
This is all encouraging. “What’s clear is that harnessing the immune system represents a new and potentially powerful strategy to clear senescent cells,” says at the University of Pittsburgh in Pennsylvania.
While there is progress on various fronts in the fight against senescent cells, the first area where such vaccines might actually make an impact is cancer, neatly bringing the promise of anti-ageing vaccines full circle. Senescent cells are much more visible to the immune system than cancer cells. Combine the two, and bingo. Cancer cells sometimes become senescent naturally. This can be induced artificially by extracting and irradiating them. have shown that injecting such cells back into the animals – or doing the same with immune cells exposed to the senescent cells – can evoke a strong anti-tumour immune response.
In one recent experiment, for example, a team at Seoul National University in South Korea took cells from tumours in mice, induced them to become senescent and then extruded them through a tiny, sieve-like membrane to create minuscule particles. Injecting the particles back from whence they came elicited a strong immune response and inhibited the growth and spread of the tumour. The researchers say the procedure is straightforward and could be developed to make personalised cancer vaccines.
As yet there are no senescent-cell vaccines in clinical trials, but efforts to test them in people are expected, according to Liu, and their potential is clear. “Further advancements are necessary, but senolytic vaccines offer a promising strategy to alleviate morbidity, ultimately improving the overall health and well-being of individuals in their later years,” he says. That is good news for my sons – and maybe I too will live long enough to benefit, helped on my way by other anti-ageing vaccines.
Graham Lawton is a staff writer at New Scientist
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