Catégorie : Blog

Recent research confirms the relatively minor role that genetics plays in our health, with the ‘exposome’, defined as the totality of exposures individuals experience over their lives affecting their health, responsible for 10 times more variation in mortality risk than genetic predisposition [1].

A paper published in Nature Medicine today, ‘Cities, communities and clinics can be testbeds for human exposome and aging research’ [2], sets out ways to start measuring how humans are affected by the exposome and furnish long-overdue evidence to design environments that enhance healthy life expectancy while reducing health and wellbeing inequalities.

The publication of the paper coincides with a tipping point for an international movement behind the ‘Human Exposome Project’, a generation on from the Human Genome Project, to understand how external exposures (including social, behavioural and geo-physical factors) and their interaction with internal factors (such as genetics and physiology), affect an individual’s health and overall resilience.

The Exposome Moonshot Forum is meeting for the first time in Washington, DC, 12-15 May 2025, to launch an unprecedented international scientific endeavour to map the combined impact of environmental factors that impact human health from conception to death.

Specific environmental factors can activate pathological pathways that contribute to disease and accelerate aging. The ability to capture, analyse and link individual data outside the medical record can show how external exposures affect a person’s health across their lifetime. These interactions can now be much better understood at an individual level and traced with unprecedented precision using artificial intelligence, representing a significant leap forward in determining the impact of the exposome at an aggregated, population health level.

This work is crucial to define new ways to address the chronic disease epidemic and ageing demographic now creating an economic drag in many nations around the world. The evidence will shape more effective public health interventions urgently needed to shift investment and policy away from an unsustainable healthcare model to one more rooted in prevention.

Tina Woods, steering committee member, Exposome Moonshot Forum; CEO, Collider Health; executive director of the International Institute of Longevity, and corresponding author says: ‘The time for the Human Exposome Project has come and I am excited to be participate in the Exposome Moonshot Forum to move it from concept to reality. We need to measure the exposome to demonstrate the return on investing in health and incentivising prevention.’

Professor David Furman, Buck Institute for Research on Aging, director of the Stanford 1000 Immunomes Project, steering committee member, Exposome Moonshot Forum, and corresponding author says: ‘At a time of increasing environmental threats to human health such as air pollution and microplastics, we have the technologies like applied artificial intelligence to help us to unravel the complex interactions between environment, immunity and health at an individual level that can be aggregated up to get a true picture of the relative impact drivers of population health’.

Professor Nic Palmarini, director of the National Innovation Centre for Ageing, and author, says: ‘We have the technologies and tools to understand the human exposome with clinics, communities and cities acting as ideal real-world testbeds to understand what solutions will promote healthier behaviours and ultimately, outcomes.’

Buck Institute

The mission of the Buck Institute is to end the threat of age-related disease for this and future generations. It is the first biomedical research institution devoted solely to research on ageing revolving around our commitment to helping people live better longer.

Media contact:

Kris Rebillot, Senior Director of Communications

415-209-2080

krebillot@buckinstitute.org

National Innovation Centre for Ageing

The UK’s National Innovation Centre for Ageing is a world-leading organisation to help co-develop and bring to market products and services which create a world in which we people live better, for longer.

Media contact:

Lynne Corner

+44 (0) 7713 245780

lynne.corner@ncl.ac.uk

International Institute for Longevity

The International Institute of Longevity (IIOL) is focused on driving global excellence, industry standards and best practice in the real-world application of longevity science into ‘longevity clinics’ as well as scientific and medical innovation to extend human healthspan, resilience and flourishing in the wider context of corporate and urban health and wellness.

Media contact:

Tina Woods

+44 (0) 7808 402032

t.woods@l-institute.com

Exposome Moonshot Forum

The Exposome Moonshot Forum on 12-15 May in Washington DC is intended to define and accelerate the future of the Human Exposome Project (HEP). The central aim of the Forum is to identify the resources, policies, and collaboration necessary to drive the successful implementation of the HEP, ensuring longevity and impact. Outcomes will centre around:

Defining clear, actionable steps toward the scalable implementation of the HEP.
Building consensus on the essential policy changes needed to support and expand research.
Establishing long-term collaborative partnerships that will bring together diverse sectors, including academia, industry, government agencies, and non-profit organizations, and divert critical funds toward this project and toward successful integration of active working groups

Media contact:

Eliza Cole, Communications Specialist

ecole28@jh.edu

Literature

[1] Argentieri, M.A., Amin, N., Nevado-Holgado, A.J. et al. Integrating the environmental and genetic architectures of aging and mortality. Nat Med (2025).
[2] Woods, T., Furman D., Palmarini N. et al. Cities, communities and clinics can be testbeds for human exposome and aging research. Nat Med (2025).

A recent country-level analysis of life expectancy among several European nations shows changes in life expectancy trends and how well-designed national policies can reduce or minimize exposure to risk factors, thus improving life expectancy [1].

Slowdown in life expectancy increase

Life expectancy has grown in high-income countries since at least 1900, except during the two World Wars and the 1918 influenza pandemic [2]. However, the speed of the growth differed; for example, since 2011, Europe’s trend towards life expectancy increases was reduced, and this was followed by a decline in life expectancy in most European countries due to the COVID-19 pandemic [3, 4].

The authors of this recent study used the data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 to compare changes in life expectancy and exposure to risk factors in the 16 founding European Economic Area countries and four UK nations.

The life expectancy at birth was defined as “the mean number of years that a newborn infant could expect to live, if he or she were to pass through life exposed to the sex-specific and age-specific death rates prevailing at the time of his or her birth, in a given country.”

They compared periods of 1990 to 2011 (pre-slowdown in life expectancy), 2011 to 2019 (slowdown in life expectancy to pre-COVID-19 pandemic), and 2019 to 2021 (COVID-19 pandemic).

Country-level analysis

When analyzed separately, all countries showed improved life expectancy from 1990 to 2011 and 2011 to 2019; however, the rate varied. Confirming the observations of bulk data analysis reported previously, the rate of life expectancy improvement was higher in the 1990-to-2011 period than the 2011-to-2019 period.

Norway was the only exception from that observation. In Norway, the trend of life expectancy increased more during the 2011-to-2019 period compared to the 1990-to-2011 period.

During the COVID-19 pandemic and post-pandemic period, all countries but Ireland, Iceland, Sweden, Norway, Denmark, and Belgium experienced an absolute fall in life expectancy, with Greece and England observing the most significant decrease.

Cardiovascular diseases, cancers, and COVID-19

The life expectancy improvements seen in the 1990-to-2011 period stem from improvements related to causes of death attributed to cardiovascular diseases and neoplasms, which are tissue masses that result from abnormal growth, whether benign or cancerous.

Unsurprisingly, the decrease in life expectancy in years 2019–21 can be attributed to the deaths from respiratory infections and other COVID-19-related health problems. However, before the COVID-19 pandemic period, reductions in improvements in life expectancy were primarily driven by cardiovascular diseases.

The researchers also made an interesting observation: “among the studied countries, those with the greatest slowdown in life expectancy improvements before the COVID-19 pandemic were generally most severely affected by COVID-19 and had some of the largest decreases in life expectancy in 2019-21.”

Avoiding risk

The researchers analyzed risk factors, attributed to different causes of death, for both sexes in all countries combined in 2019. The top three risk factors for cardiovascular disease were high systolic blood pressure, dietary risks, and high LDL cholesterol. For neoplasms, the top risk factors included tobacco smoke, dietary risks, and occupational risks.

The levels of different risk factors changed with time, such as exposure to tobacco smoke; even though it is still a high population risk, it has decreased over time. On the other hand, BMI has increased in all countries, and dietary risks, high alcohol use, and low physical activity remain high in most.

The authors also point to high LDL cholesterol and systolic blood pressure, which declined until before 2011; however, this trend reversed after 2011 in many countries.

The danger of a risk factor varies by the time between exposure to it and the start of the disease that it causes, the length of exposure, and its interactions with other risk factors. Unfortunately, this dataset doesn’t provide some of that information.

Funding healthcare

Following their analysis, the authors discuss governmental policies and their impact on life expectancy. For example, they mention national fiscal and healthcare policies that impact the population’s life expectancy, especially for people in the worst socioeconomic situations.

An example of policies aimed at increase access to healthcare are Belgian, French, and Norwegian national policies, which, in recent years, have focused on increasing cancer diagnosis and treatment. The authors hold that these policies improved life expectancy related to neoplasms between 1990 and 2019. Additionally, some research has suggested that funding cuts to health, social care, and welfare since 2010 contributed to the slowdown in life expectancy improvement [5, 6].

Diet and physical activity are the foundation of health and longevity

Diagnosis and treatment happen after a person suffers from a disease. Preventing diseases from occurring through proper diet and physical activity might be more effective at increasing life expectancy.

The authors give examples of how healthy food consumption can be influenced by effective policy. An example is Norway, which had implemented a sugar tax as early as 1922. Similarly, starting in the 1980s, the Norwegian government talked with the industry about reducing the amount of salt in food products. This was complemented by Norway’s ‘Action Plan on Nutrition 2007–2011’, which, apart from education, also focused on other nutritional aspects, such as increasing focus on nutrition in a health care setting.

This broader approach has proven more effective than focusing only on education and voluntary dietary changes. Apart from diet, physical activity is the cornerstone of health and reducing premature mortality. Unfortunately, accordingly to this analysis, at the population level, there were no improvements in the levels of even low physical activity across the studied countries. The authors believe that systematic strategies and incentives are necessary to change that.

Ultimately, the authors intend for policymakers to utilize this analysis as a guide to reverse their countries’ slowdown in life expectancy improvement. They also hold that countries that implement successful policies can be used as examples for others to follow.

Literature

[1] GBD 2021 Europe Life Expectancy Collaborators (2025). Changing life expectancy in European countries 1990-2021: a subanalysis of causes and risk factors from the Global Burden of Disease Study 2021. The Lancet. Public health, 10(3), e172–e188.

[2] Roser M. (2020) The Spanish flu: the global impact of the largest influenza pandemic in history. https://ourworldindata.org/spanish-flu-largest-influenza-pandemic-in-history

[3] Raleigh VS. (2019) Trends in life expectancy in EU and other OECD countries. OECD Health Working Papers 108. https://www.oecd.org/en/publications/trends-in-life-expectancy-ineu-and-other-oecd-countries_223159ab-en.html

[4] Organisation for Economic Co-operation and Development, EU. (2018) Health at a glance: Europe 2018: state of health in the EU Cycle. https://www.oecd.org/en/publications/health-at-aglance-europe-2018_health_glance_eur-2018-en.html

[5] Alexiou, A., Fahy, K., Mason, K., Bennett, D., Brown, H., Bambra, C., Taylor-Robinson, D., & Barr, B. (2021). Local government funding and life expectancy in England: a longitudinal ecological study. The Lancet. Public health, 6(9), e641–e647.

[6] McCartney, G., McMaster, R., Popham, F., Dundas, R., & Walsh, D. (2022). Is austerity a cause of slower improvements in mortality in high-income countries? A panel analysis. Social science & medicine (1982), 313, 115397.

Applying statistical methods to a large dataset spanning almost 300 species, scientists found a positive correlation between body size and cancer prevalence [1]. Other researchers dispute that these findings invalidate the famous paradox.

A paradox of size

Cancer has forever been a mortal enemy of multicellular life. Sometimes, the cell’s “program” malfunctions, causing it to divide uncontrollably, until its progeny takes over the organism and kills it. This can happen to almost any cell, and one cell is enough.

A logical conclusion is that the more cells an animal has, the greater its risk of developing cancer. Hence, larger animals with many times more cells should be getting cancer much more frequently, but this does not appear to occur in nature. Instead, lifespan is positively correlated with body size (barring a few outliers), and small animals often get more cancer, not less. For instance, cancer is a highly prevalent cause of death in lab mice.

This became known as Peto’s paradox, after Sir Richard Peto, a British epidemiologist and statistician, who first articulated the idea in 1977 while studying cancer risks in different species. Of course, there’s nothing mystical about it: many large, long-lived species have developed superior anti-cancer defenses, such as DNA repair mechanisms, robust immune systems, and enhanced methods of removing cancerous cells through apoptosis. A lower cell division rate in some large species might also explain a part of the paradox.

For example, elephants have at least 20 copies of the TP53 gene, which plays crucial roles in detecting and repairing DNA damage and in triggering cell death in potentially cancerous cells, while humans have just one. Studying those mechanisms is a rapidly growing field in geroscience.

The correlation between body size and cancer

Since Peto’s original observation, several studies have investigated this question. Some of them found no correlation between cancer prevalence and body sizes, seemingly confirming the paradox [2]. However, those earlier studies were plagued by low data availability; after all, it’s hard to amass enough necropsies for multiple species.

Enter this new paper by scientists from the University of Reading, University College London and the Johns Hopkins University School of Medicine. This paper was published in Proceedings of the National Academy of Sciences (PNAS) and ambitiously titled “No evidence for Peto’s paradox in terrestrial vertebrates.”

The paper is based on a dataset created for a slightly earlier study by Compton et al. [3] The unprecedentedly large dataset consists of 16,049 necropsy records for 292 species, which made better statistical analysis possible. Interestingly, that paper did not reach the same definitive conclusion but instead highlighted “limitations to Peto’s paradox, by showing that large animals do tend to get somewhat more neoplasms and malignancies when compared with smaller animals.”

The authors of the PNAS paper claim to have applied more robust statistical analysis to the same dataset, which allowed them to extract a clearer signal. Professor Chris Venditti, senior author of the research at the University of Reading, said, “Everyone knows the myth that elephants are afraid of mice, but when it comes to cancer risk, mice are the ones who have less to fear. We’ve shown that larger species like elephants do face higher cancer rates—exactly what you’d expect given they have so many more cells that could go wrong.”

The researchers separately analyzed birds and mammals, which stop growing at certain points in their life, along with amphibians and reptiles, many of which never do. In the first subset, the authors controlled for body mass, while in the second, for body length (which itself might have affected the results).

They found a significant positive association between neoplasia (this included both benign and malignant tumors, which were strongly correlated) and body size. For mammals, the relationship was β = 0.129, indicating a relatively flat slope (a linear relationship would have β = 1). In amphibians and reptiles, the correlation was stronger: β = 0.433. “Across all four vertebrate classes, larger species have an increased prevalence of malignancy compared to smaller species, thus demonstrating no evidence of Peto’s paradox,” the paper concludes.

The paradox is dead, long live the paradox

However, this suggests a narrow reading of Peto’s paradox as nothing short of zero positive correlation between cancer and body size. “The conclusion of this paper is not supported by the results,” said Dr. Vera Gorbunova of the university of Rochester, a researcher of long-lived species who was not involved in this study. “Even if there is a small statistical trend towards increased cancer with increased body size, it is not proportional to the number of cells or cell divisions experienced by larger species. An elephant still has much lower cancer incidence than a mouse. The authors themselves conclude that larger species have evolved better control of the cell cycle. This means they did evolve additional anticancer defenses, which is what Peto’s paradox posits.”

Indeed, the authors point to some instances of animals clearly “outsmarting” cancer, with elephants having 56% lower cancer rates than expected for their body size, and naked mole rats, rodents famous for their longevity, performing even stronger. On the opposite side of the spectrum lie the notoriously cancer-prone ferrets and opossums. Interestingly, bats and turtles, highlighted in Compton et al. as supporting Peto’s paradox, are not mentioned in this new study.

Dr. Joanna Baker, co-author from the University of Reading, said, “When species needed to grow larger, they also evolved remarkable defenses against cancer. Elephants shouldn’t fear their size—they developed sophisticated biological tools to keep cancer in check. It’s a beautiful example of how evolution finds solutions to complex challenges.”

An important aspect of this study is that the researchers were able to count in some evolutionary differences. In particular, they found that species that evolved larger body sizes more rapidly, such as through a series of evolutionary ‘bursts’, were more likely to have stronger anti-cancer defenses.

“These studies represent a more comprehensive quantitative evaluation of some of the theories of evolution of aging and life history strategies,” said Dr. Emma Teeling of the University College Dublin, who also was not involved in this study. “Collecting these malignancy and life history studies requires decades if not centuries for long-lived species. This is why these studies are confined to captive species, where perhaps what was measured is actually the potential stress of captivity rather than true rate of malignancy. We are limited to species that we are able to maintain in captivity, which are not necessarily those that have evolved the most robust and therefore the most interesting anti-cancer mechanisms.”

“The authors detected a signal of evolution in action, where indeed with increased body size, there is a trend towards increased cancer incidence that then gets compensated by evolution of additional tumor suppressor mechanisms,” Gorbunova said. “Overall, I think the title of the paper is somewhat ‘sensationalized’. If this study found that upon certain phylogenetic comparisons larger species have slightly increased cancer risk, it does not eliminate Peto’s paradox.”

“The outliers in both of these studies, the species that were observed to have more or less than predicted cancer regardless of the methods used, are the most interesting candidates,” Teeling added. “Some of these species have been the focus of previous anti-aging research, such as the naked mole rat. Both studies will stimulate new ways to consider the evolution of cancer and anti-cancer mechanisms across the tree of life, new methods, datasets, and conclusions.”

Literature

[1] Butler, G., Baker, J., Amend, S. R., Pienta, K. J., & Venditti, C. (2025). No evidence for Peto’s paradox in terrestrial vertebrates. Proceedings of the National Academy of Sciences, 122(9), e2422861122.

[2] Boddy, A. M., Abegglen, L. M., Pessier, A. P., Aktipis, A., Schiffman, J. D., Maley, C. C., & Witte, C. (2020). Lifetime cancer prevalence and life history traits in mammals. Evolution, medicine, and public health, 2020(1), 187-195.

[3] Compton, Z. T., Mellon, W., Harris, V. K., Rupp, S., Mallo, D., Kapsetaki, S. E., … & Boddy, A. M. (2025). Cancer prevalence across vertebrates. Cancer discovery, 15(1), 227-244.