That trend has prompted researchers to investigate a provocative possibility: Are younger generations accumulating biological damage more quickly, causing their bodies to age faster than expected?

A study led by researchers at Washington University School of Medicine in St. Louis offers evidence that this may be happening. The team found signs that younger generations are aging more rapidly on a biological level than older generations did at comparable ages.

Scientists are still working to understand what is driving these changes. The question is being investigated through international efforts involving research members of Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, and Cancer Grand Challenges, a global initiative co-founded by the National Cancer Institute and Cancer Research U.K.

Importantly, the researchers also found that accelerated biological aging was associated with a greater risk of early-onset cancers among younger generations. In general, early-onset cancers are those diagnosed at age 55 or younger.

A Gap Between Biological Age and Actual Age

Chronological age simply measures how many years a person has been alive. Biological age, by contrast, reflects how old the body appears based on measurable changes in cells, organs, metabolism, and other physiological systems.

According to the researchers, cancer risk increased as the difference between biological age and chronological age grew. People from more recent generations tended to have larger gaps than those born earlier, suggesting their bodies appeared biologically older at the same chronological age.

That generational shift could help explain at least part of the rise in cancer among younger adults.

The team also found that aging did not appear to affect every organ system in the same way. Faster aging in specific parts of the body was associated with particular cancers. An immune system that appeared biologically older, for example, was linked to early-onset lung cancer. Older-appearing fat tissue was associated with early-onset colorectal cancer.

The findings were published in the journal Nature Medicine.

Researchers say measurements of accelerated aging could eventually help doctors identify younger people who face unusually high cancer risks, potentially allowing prevention or screening to begin earlier.

“Our ultimate goal is to decode how modern environments become biologically embedded to drive cancer risk, transforming prevention from broad recommendations to personalized interventions,” said Yin Cao, ScD, a molecular epidemiologist and an associate professor of surgery and of medicine at WashU Medicine. “This brings us closer to identifying risk earlier and developing prevention strategies that are tailored to an individual’s biology.”

Looking Beyond Individual Cancer Risk Factors

Cao’s team has previously studied numerous factors that can shape cancer risk over a person’s lifetime, including obesity, metabolic dysregulation, alcohol consumption, sedentary behavior, poor diet quality and cesarean delivery.

Each of these factors can provide clues about why cancer develops at younger ages. However, no single factor appears to explain very much of the overall trend on its own.

That led Cao, who is also a research member of Siteman, and her colleagues to look for a broader way of measuring how many different influences may work together over time to increase cancer susceptibility.

Support from Cancer Grand Challenges has allowed Cao, as co-lead of Team PROSPECT, to investigate this question on a much larger scale.

For the new study, the researchers examined data from more than 154,000 young adults enrolled in the UK Biobank, which contains extensive biological, health, and lifestyle information.

They also analyzed more than 10,000 participants in the United States who are part of the National Institutes of Health’s (NIH) All of Us Research Program, an initiative designed to create a comprehensive health database involving more than 1 million people living in the U.S.

Measuring How Fast the Body Is Aging

To determine biological aging, the researchers, including first author Ruiyi Tian, a doctoral student in the Cao lab, looked at two different scales.

One was systemic aging, which measures aging across the body as a whole. The other was organ-specific aging, which estimates how rapidly individual organs or biological systems are aging.

For systemic aging, the researchers relied on established approaches that use clinical biomarkers, including PhenoAge and the Klemera-Doubal Method. They also used a metabolomic age score designed to capture age-related patterns in a person’s metabolism.

PhenoAge, for example, uses nine blood biochemistry markers to estimate biological aging. These include albumin, made by the liver, and creatinine, a waste product removed by the kidneys.

For organ-specific aging, the researchers analyzed blood proteomic data, which measure levels of numerous proteins associated with specific organ systems. Those protein patterns were then used to estimate the biological age of individual organs.

The team calculated the average difference between biological and chronological age within each birth cohort. They then used standard deviation to measure how far each group differed from the overall study average. Standard deviation is a measure of how spread out data points are around the average.

Younger Generations Show Older Biological Profiles

The generational differences were apparent in both the UK and U.S. populations.

Among UK participants, people born between 1965 and 1974 had systemic aging that was 23% of one standard deviation higher than people born between 1950 and 1954, even after chronological age was taken into account.

Put more simply, members of the younger generation tended to have slightly older biological profiles than members of the older generation when researchers compared them at the same chronological age.

An even larger difference appeared in the U.S. data.

Participants born between 1990 and 1999 had systemic aging that was 92% of one standard deviation higher than those born between 1965 and 1969.

The researchers then examined whether these biological aging differences were connected to cancer.

Faster Aging Linked to Early-Onset Cancer

Greater systemic aging in the younger group was associated with an 8% increased risk of early-onset solid cancers. The strongest associations involved lung, gastrointestinal, and uterine cancers.

When the participants were separated into three groups according to their level of systemic aging, another pattern emerged.

People with the most advanced systemic aging had a 15% increased risk of early-onset solid cancer compared with participants showing the least advanced aging.

The association remained even after researchers accounted for inherited genetic cancer risks and genetic susceptibility to accelerated aging.

Looking at individual biological systems revealed more specific connections.

Advanced immune system aging was associated with a higher risk of early-onset lung cancer. Advanced adipose (fat) tissue aging was linked to a higher risk of early-onset colorectal cancer.

“If we can identify younger people with the highest cancer risk when they are still healthy, we can focus on prevention and early-detection strategies for the individuals who will benefit most from early interventions,” Cao said.

Searching for the Causes of Cancer in Younger Adults

The research is part of Team PROSPECT, a Cancer Grand Challenges team co-led by Cao.

Cancer Grand Challenges is an international research funding initiative co-founded by Cancer Research UK and the National Cancer Institute (NCI). It brings together scientists from different specialties and countries to investigate some of the most difficult problems in cancer research.

One of those problems is explaining why early-onset cancers are becoming more common.

“Right now, we don’t have a definitive answer to what’s driving the rise of early-onset cancers around the world, but studies like this are helping us piece together the bigger picture, showing that cancer may be influenced not just by changes inside individual cells, but by wider changes happening across the body as a whole,” said David Scott, PhD, director of Cancer Grand Challenges. “Research on this scale is possible through Cancer Grand Challenges, which brings together scientists from different fields around the world to tackle these complex questions together.”

Cao and her colleagues are now working to better understand why cancer is increasingly affecting younger generations.

A major focus is determining how changes in the environment, lifestyle and society may leave long-lasting biological marks on the body. Those effects could include accelerated aging as well as other signs that make some people more vulnerable to disease.

By tracing how these risks accumulate throughout life, researchers hope to uncover more of the biological origins of early-onset cancers.

The ultimate goal is not simply to understand why cancer develops earlier, but to identify people at elevated risk while they are still healthy. That could make it possible to move prevention and screening earlier and tailor interventions to an individual’s biology, shifting cancer care toward stopping disease before it begins.

This work was part of the PROSPECT team supported by the Cancer Grand Challenges initiative funded by Cancer Research UK, grant numbers CGCATF-2023/100043 and CGCATF-2023/100037; the National Cancer Institute of the NIH, grant numbers OT2CA297577 and OT2CA297576; the French National Cancer Institute; and the Bowelbabe Fund for Cancer Research UK. The project was also supported by grants from NIH/National Cancer Institute, grant number R37CA246175; the NIH/National Institute of Diabetes and Digestive and Kidney Diseases, grant number P30DK052574; the Alvin J. Siteman Cancer Center through the Foundation for Barnes-Jewish Hospital. Further support was provided by a pre-doctoral fellowship in the Cancer Biology pathway supported by NIH Molecular Oncology Training Grant T32CA113275 to Washington University School of Medicine in St. Louis; the Pediatric Gastroenterology Research Training Program grant T32DK077653 to Washington University School of Medicine in St. Louis; the Washington University School of Medicine in St. Louis Institute of Clinical and Translational Sciences, grant number UL1TR002345; and the Foundation for Barnes-Jewish Hospital. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

The issue centers on the inductive effect, a fundamental idea in structural organic chemistry used to describe how atoms influence the distribution of electrons within molecules. The researchers’ 2024 research concluded that textbooks had been describing this effect incorrectly for almost 100 years.

That work has already begun to influence chemistry education. Two A-level exam boards have since announced reviews of how they teach the inductive effect and directly cited the research as part of the reason for doing so.

A new paper in the Journal of Chemical Education now expands on those findings and examines what they could mean for the way one of chemistry’s foundational concepts is taught.

Rethinking a Core Idea in Organic Chemistry

Researchers led by Cardiff University and the University of Newcastle in Australia are proposing a simpler and more consistent explanation of the inductive effect. They believe the revised approach could make the concept easier for students to understand while giving scientists a clearer framework for interpreting how molecules behave.

“The inductive effect is a foundational concept in chemical bonding, because it is used to explain how electrons are distributed between atoms in molecules,” explains Dr. Mark Elliott, lead author of the study from Cardiff University’s School of Chemistry.

“Everyone who studies chemistry beyond GCSE, or equivalent, learns about it.”

The implications are particularly important for organic chemistry, according to the researchers. Organic chemists routinely study chains of atoms that form the molecular foundations of medicines, advanced materials, agrochemicals, polymers and many other technologies used in everyday life.

Understanding how electrons are distributed through those structures can help chemists explain why molecules have particular properties and why they undergo certain chemical reactions.

A Chemical Effect That May Stop After One Bond

For decades, organic chemistry textbooks have generally taught that the influence of certain atoms can travel through three or four bonds within a molecule. According to the traditional explanation, that influence becomes progressively weaker as it moves farther from the original atom.

The researchers say the evidence paints a different picture.

“In our latest paper, we find that the inductive effect does not behave in this way,” Dr. Elliott says.

“Instead, we show that the inductive effect in a neutral molecule does not extend beyond one bond. As a result of this, we need to refine explanations for certain types of reactivity. This can provide a more coherent framework for explaining chemical structure and reactivity.”

Rather than treating the inductive effect as an influence that gradually travels along a chain of atoms, the team’s interpretation confines it to the bond directly connected to the relevant atom in a neutral molecule.

That seemingly small change could matter because the inductive effect is commonly used to explain molecular structure and chemical reactions. If its reach has been misunderstood, other explanations built around the traditional model may also need to be reconsidered.

Evidence Hidden Across the Scientific Literature

The researchers did not arrive at the conclusion from a single experiment. They brought together evidence that was already scattered throughout scientific research and combined it with their own consistent data set.

“While some data supporting our conclusions is already available within the research literature, it is not widely known. What we have done is pull all the existing data together, supported by our own coherent data set, to show the generality and teaching implications of this approach.

“It is important to teach the basics correctly. So, if we get rid of this incorrect stuff, we can start using the correct explanation for all aspects.”

The international collaboration grew after Dr. Elliott encountered work by Dr. Edwin Johnson of the University of Newcastle and Dr. Kasimir Gregory of the University of New England. Their research examined how electronegative elements affect acidity and also produced results that did not fit conventional textbook descriptions.

“We realized that the discrepancy between modern computational data and textbooks was larger than we had anticipated.”

Modern Tools Challenge Longstanding Chemistry Ideas

Questioning such an established concept was not something the researchers initially approached lightly.

“We didn’t initially feel comfortable challenging the established wisdom. Some of the names associated with the inductive effect are ‘legends’ of our discipline. We certainly aren’t smarter than those pioneers, of course. But we have better tools nowadays and so have been able to look at things in a different way – examining molecular structures directly whereas they had to draw indirect conclusions from limited experimental data.”

Earlier generations of chemists developed many foundational ideas using the experimental techniques available at the time. Modern computational methods now allow researchers to examine molecular structures and electron distributions in ways that were not possible when many textbook explanations were first developed.

By clarifying what the inductive effect does and how far it extends, the researchers hope other influences on molecular behavior can also be understood more accurately.

Why Correcting Chemistry Textbooks Matters

The researchers argue that getting foundational concepts right is important far beyond introductory chemistry courses. Misunderstandings introduced early in a student’s education can follow them into more advanced chemistry and eventually into scientific research.

“If a foundational concept is taught inaccurately, misunderstandings can carry into more advanced science and research,” adds Dr. Edwin Johnson, Lecturer at the University of Newcastle, Australia, who co-authored the paper.

“By revisiting a long-standing textbook explanation with modern tools, our work aims to improve chemistry education and strengthen the conceptual foundations that support chemical innovation.”

The researchers hope their proposed explanation will ultimately give students a more consistent way to understand chemical bonding while providing scientists with a stronger conceptual basis for studying molecular structure and reactivity.

The paper, ‘Rethinking the Nature and Extent of Inductive Effects in Organic Compounds’, is published in the Journal of Chemical Education.

The findings suggest that breast cancer patients with vitamin D deficiency (below 30 nmol/L) could potentially benefit from supplementation before undergoing a radical mastectomy, a major operation in which an entire breast is surgically removed.

Vitamin D May Play a Role in Pain

Vitamin D is best known for its role in bone health, but growing evidence suggests it may also influence how the body senses and processes pain. Researchers believe this could be related to vitamin D’s effects on inflammation and the immune system, both of which can influence pain responses.

Vitamin D deficiency is also frequently reported among people with breast cancer, prompting researchers to investigate whether low levels might affect pain following surgery.

To explore that possibility, researchers conducted a prospective observational study at Fayoum University Hospital in Egypt between September 2024 and April 2025. A prospective study follows patients forward in time, while an observational study tracks what happens without assigning participants to different treatments.

The study included 184 breast cancer patients scheduled to have one entire breast surgically removed.

Comparing Patients With High and Low Vitamin D

Half of the participants were classified as vitamin D deficient (below 30 nmol/L), while the other half had vitamin D levels considered sufficient (above 30 nmol/L).

The two groups were broadly similar. Patients in the vitamin D deficient group had an average age of 44, compared with 42 in the vitamin D sufficient group.

Everyone received the hospital’s standard treatment during and after surgery. Importantly, the doctors and other clinical staff caring for the patients did not know their vitamin D status, reducing the chance that this information could influence pain treatment.

During surgery, patients received fentanyl, a powerful opioid used to control acute pain. After surgery, every patient received paracetamol through an intravenous drip every 8 hours.

Patients could also give themselves tramadol (another opioid analgesic) by pressing a button connected to a patient-controlled pain relief system. This allowed researchers to track how much additional opioid medication each person needed.

Low Vitamin D Linked to More Pain

Patients rated their pain immediately after surgery and again at 6 hours, 12 hours, 18 hours and 24 hours. Researchers also recorded nausea, vomiting, sedation levels, and how long patients remained in the hospital.

A clear difference emerged during the first day of recovery.

Patients with vitamin D deficiency were three times more likely to report moderate to severe postoperative pain at any point during the first 24 hours compared with patients who had sufficient vitamin D levels.

However, none of the patients in either group experienced what researchers classified as severe pain (7 or over on a scale of 0 to 10). The difference between the groups came entirely from moderate pain (4-6 on the pain scale).

Patients With Low Vitamin D Used More Opioids

The difference also appeared in the amount of pain medication patients required.

Those with vitamin D deficiency received an average of 8 μg more fentanyl during surgery. Researchers described that difference as modest.

The gap was much larger after surgery.

Patients in the vitamin D-deficient group used substantially more tramadol (112mg) than patients with sufficient vitamin D. Patients controlled the medication themselves, up to a maximum dose of 50mg per hour.

Greater opioid use matters because these drugs can cause side effects such as nausea, vomiting, drowsiness, and confusion. They also carry risks of dependency and addiction.

Postoperative nausea was more common among patients with vitamin D deficiency. Vomiting occurred only in the deficient group, although the difference was small and was not statistically significant, meaning researchers could not confidently rule out chance as the explanation.

The Study Cannot Prove Cause and Effect

The findings point to a potentially important connection between vitamin D and surgical pain, but the researchers emphasized several limitations.

Because the study was observational and conducted at a single center, it cannot show that vitamin D deficiency directly caused patients to experience more pain or use more opioids.

Researchers also did not measure inflammatory markers, so they could not investigate the biological mechanisms that might explain the relationship between vitamin D and pain.

The study also lacked information on several factors that could potentially influence postoperative pain, including anxiety, depression, cancer stage, cancer treatment, and sleep disturbance before surgery.

Despite those limitations, the researchers conclude, “Vitamin D deficiency is associated with a higher occurrence of moderate to severe postoperative pain and increased opioid consumption in patients undergoing unilateral modified radical mastectomy.”

They suggest, “Preoperative vitamin D supplementation in breast cancer patients with vitamin D levels below 30 nmol/L may have a role in modulating postoperative pain.”