The Early Onset of Cancer in Young Adults is linked to ‘Accelerated Aging’– Modifiable by a Healthy Lifestyle

The widely publicized cancer of Kate, Princess of Wales, sheds light on a very worrisome trend: the rising incidence rate of certain early-onset cancers, especially solid tumors, in young adults.

According to recent studies, the incidence of early-onset cancers – defined as those diagnosed in people under the age of 50 – is on the rise, not only in the United States but worldwide. A study published in the British Medical Journal in 2023 found that between 1990 and 2019, this incidence rose by almost 80% from 1.82 million to 3.26 million, while the number of deaths attributable to early forms jumped by almost 30% over the same period.

In their 2022 research findings, leading scientists at Harvard Medical School went so far as to call early-onset cancers an 'emerging global epidemic'.

A new study by Tian et al, presented at the annual meeting 2024 of the American Association for Cancer Research (AACR), showed an uptick in new cases of various cancers, in particular lung (42%), uterine (36%) and gastrointestinal (22%). Looking for new clues as to why some types of cancer are on the rise in young adults, Tian et al discovered a close connection to accelerated aging.

They hypothesized that accelerated aging – when biological age surpasses chronological age –may be a major risk factor for the development of early-onset cancers in young adults.

What’s the difference between biological age and chronological age?

A growing number of experts agree that age is not just the number of candles on a birthday cake, but also the degree of wear and tear on the body due to lifestyle, stress, and genetics, often referred to as a person's biological age.

The notion of chronological age reflects how many years a person has been alive. It is the main risk factor for chronic disease, cancer, and death. Although age correlates with and presumably acts through the accumulation of biological changes*, every individual undergoes these changes at different rates. Therefore, the notion of chronological age serves only as an imperfect surrogate for time-related biological changes.

Unlike chronological age, biological age refers to a person's physical condition and physiological processes; as such, it is considered to be modifiable. Biological aging is influenced by diet, physical activity, mental health, and environmental stress factors. A growing body of evidence suggests that younger generations may age faster than expected, probably due to earlier exposure to various risk factors and environmental insults.

*Increasing age correlates with a variety of molecular changes, including telomere shortening, differential gene expression, and mitochondrial decline, which have in turn been investigated as potential biomarkers for the prediction of disease onset and mortality.

Faster biological aging may be driving early-onset cancer in young adults.

The new study by Tian et al, presented at the annual meeting 2024 of the American Association for Cancer Research (AACR), prospectively investigated the association between accelerated aging – when biological age surpasses chronologic age – and the rising global incidence of early-onset cancers among recent generations. Researchers found that accelerated aging is much more common in recent birth cohorts and may emerge as a risk factor for the development of early-onset solid cancers.

To examine the association between biological age and cancer risk in younger individuals, Tian and colleagues looked at medical records of 148,724 people ages 37 to 54 who are participants in a large data registry called the U.K. Biobank.

They calculated each participant’s biological age using 9 biomarkers found in blood and shown to correlate with biological age: albumin (declines with age), alkaline phosphatase (tends to increase with age), creatinine (measure of kidney function declines with age), C-reactive protein (higher levels correlate with faster aging), glucose (tends to stay higher for longer after meals with age), mean corpuscular volume (increases with age), red cell distribution width (increases with age), white blood cell count (high end of normal range), and lymphocyte proportion (relates to immune function and decreases with age). They plugged these 9 values into an algorithm called PhenoAge that served to calculate each person’s biological age.

‘Individuals whose biological age was higher than their chronological age were defined as having accelerated aging’.

The researchers discovered a total of 3,190 cases of early-onset solid cancer. They assessed aging across different age groups and determined that people born in or after 1965 had a 17% higher risk of accelerated aging, compared to those born between 1950 and 1954.

Next, the researchers examined the link between accelerated aging and the risk of early-onset cancers. They found a direct link between accelerated aging and increased risk of early onset of lung (42%), uterine (36%) and gastrointestinal (22%) cancers.

The study's authors conclude that validation studies in diverse populations, as well as further research aimed at uncovering the mechanisms driving accelerated aging and early-onset cancers, will be needed to guide the development of new preventive and therapeutic approaches.

Accelerated aging triggered by gut microbiome, stress and lifestyle – not chronological age.

A growing body of evidence suggests that the gut microbiome – the collection of microbes such as bacteria, fungi and viruses that live naturally in the human body – may play a pivotal role in immune system dysregulation and disease susceptibility.

The intestinal microbiome is a powerful transducer of environmental signals, capable of modifying disease risk in all age groups. It can extend life expectancy by regulating metabolic processes and the immune system, but also, in the case of dysbiosis, predispose to diseases such as inflammatory bowel disease or colorectal cancer.

A study presented at the annual meeting of the American Society of Clinical Oncology in 2023 suggests that the gut microbiome may play a role in the development of colorectal cancer in young adults.

The increase in early-onset cancers is most probably linked to lifestyle. According to the American Cancer Society (ACS), nearly half of all cancers are related to lifestyle factors that impact our biological age, such as: excessive calorie consumption, lack of exercise, mental health disorders, poor diet, smoking, alcohol and stress.

Stress is part of life. However, chronic stress can weaken the immune system and lead to diseases such as cancer. Among other things, stress hormones inhibit a process known as anoikis, which kills and eliminates diseased cells to prevent them from spreading. In addition, chronic stress increases the release of a number of growth factors that stimulate blood flow, potentially accelerating the development of cancerous tumors.

Personal and economic costs

Needless to say, that being diagnosed with a cancer is a devastating experience. What's more, diagnosing younger people is more difficult, as their symptoms are usually more muted, while tumors tend to progress more aggressively.

Additionally, patients with early-onset cancer diagnoses are impacted differently, both mentally and physically, then those with average-onset, which is defined as cancer in ages 50 and up. There are considerations relating to sexual health, lifestyle, mental health, fertility, etc. that need to be taken into account. For women in particular, fertility may represent a huge differentiating factor.

The human and economic costs of cancer in adolescents and young adults (aged 15-39) are staggering: in the U.S., total healthcare costs amount to $23.5 billion, or $259,324 per person over a lifetime. This figure includes the cost of lost productivity, which amounts to $18 billion. Most of these costs are incurred by the survivors themselves, as many younger adults have no health insurance.

At a societal level, the costs associated with the burden of disease – defined as the years of healthy life lost due to morbidity, disability, and mortality – amount to $96 billion, bringing the total cost to $119.5 billion, or $1.319 million per patient over a lifetime (Journal of Clinical Oncology, 41 :3260-3268, 2023).

How can we slow premature aging and prevent early-onset cancer?

Using life years as a measure of aging simply doesn't reflect how the human body ages. In contrast, the concept of biological age, which relies on functional metrics, provides a much clearer picture of an individual's physiological state and susceptibility to disease.

This is why the distinction between 'chronological age' and 'biological age' is crucial to identify those who have a young chronological age but show signs of rapid aging, with a dual purpose:

1) Early and intensive lifestyle intervention: improve eating habits along with regular physical activity to help reduce biological aging. As it happens, today, social media dictates how people behave, including their eating habits and declining physical activity – with so much 'free time' spent staring at the screen – let alone the emotional exhaustion caused by constantly chasing the virtual world.

2) Customized screening of young people showing signs of accelerated aging or having unusual symptoms allows for early detection of cancers. At present, young adults without a family history or other risk factors are not routinely screened for most cancers.

Cancer prevention remains the best strategy for fighting the disease. While symptoms may vary for different types of cancer, a good rule of thumb is to report ‘any new or persistent symptoms’ you experience to your doctor without delay. Being aware and seeing a doctor regularly can help prevent and treat cancer when cure is still an option.

It may not be prime time yet, but PhenoAge's ability to assess accelerated aging may one day allow doctors to identify patients likely to benefit from drugs currently in development called senolytics (drugs that target and eliminate damaged, aging cells). The amazing simplicity of determining your biological age using 9 blood parameters, which are checked every time you get bloodwork done, holds promise for the future.

Final thoughts

The steady rise in the incidence of early-onset cancers in young adults is now well-documented and a reality. Ongoing research suggests that accelerated aging may be a major risk factor. The strongest correlations were observed for cancers of the lung, gastrointestinal tract and uterus.

It is important to emphasize that this accelerated aging could be curbed to a large extent by a healthier lifestyle, a balanced diet and effective stress management, along with targeted surveillance, diagnostic and treatment measures.

The sharp rise in early-onset cancers underscores the need for intensified research in all areas: population sciences, behavioral health, public health and basic sciences. Further studies of the mechanisms of accelerated aging and their link to the pathophysiology of early-onset cancers are essential to the development of new prevention and treatment strategies.