Mois : septembre 2024

A new study analyzed how being an elite athlete in various sports affects human lifespan. Some of the results were surprising [1].

Elite sports and aging

Longevity enthusiasts have long wondered if professional athletes live longer than the general population and what sports show stronger associations with lifespan. In a new study published in the journal GeroScience, a group of scientists from Holland attempted to research this using data on tens of thousands of elite athletes born between 1862 and 2002. The sample encompassed 183 countries and 44 sports disciplines.

The data was collected by the researchers themselves using public sources. The effect on lifespan was determined by comparing the ages of athletes with those of the corresponding reference populations, and the results were adjusted for sex, year of death, and country. The vast majority of the athletes were males, which limited the study’s applicability to the female population.

Volleyball, what’s wrong with you?

The study yielded both expected and intriguing results. In males, the highest life extension was observed for pole vaulting and gymnastics (8.4 and 8.2 years, respectively). Racquet sports and mixed track and field were not far behind (5.7 years both). In general, most sports were associated with statistically significant life extension, with soccer and wrestling showing some of the smallest positive effect sizes.

However, there were several outliers. Sumo was associated with a massive 9.8-year negative effect on lifespan. Surprisingly, volleyball came in second (-5.4 years), followed by mountaineering (-3.8 years), martial arts (-2.5 years), and handball (-2.2 years). Other notable sports with negative, albeit smaller, effect sizes, were ice hockey (-0.8 years) and boxing (-0.6 years).

Since the sample contained much fewer female athletes, associations for them were not as clear-cut. From the limited list of sports in the female subset, only golf and racquet sports showed significant positive effects on lifespan (3.2 and 2.8 years, respectively).

Interestingly, contrary to what was observed in males, most sports seemed to have negative effects on female lifespan. Those with significant effect sizes included basketball (-6.7 years), table tennis (-4.8 years), cricket (-4.2 years), mixed track and field (-2.4 years), sprinting (-2.1 years), and skiing (-2 years).

Interpreting the results

Populational studies like this one can only show correlations and not causative effects, and interpreting their results can be notoriously difficult due to the abundance of confounding factors. The researchers discuss, at length, possible explanations for their findings but admit that those are mere speculations.

One hypothesis that seems plausible is that sports that combine aerobic and anaerobic activity, both of which are associated with health and longevity [2], produce the largest positive effect. However, this was not the case for martial arts and boxing, most probably because of the high risk of injuries.

Sumo is a great illustration of the deleterious effects of a high-calorie diet and obesity that cannot be offset even by high levels of exercise. That said, the length of a professional career in sports usually does not exceed two or three decades, and in later life, the amount of physical activity is expected to decline.

The origins of the sex gap observed in this study are unclear. The researchers note that the male population, especially in earlier cohorts, is more prone to unhealthy habits, and “participation in sports may prompt males to minimize such habits, leading to a more profound impact of sports on their lifespan.”

Females, on the other hand, lead healthier lives on average, which decreases the populational effect of giving up unhealthy habits. Differences in aging processes in men and women, such as menopause, might account for some of the effect, too.

Various studies have tried to understand the health impact of extremely strenuous exercise, which elite athletes routinely engage in. The results are largely inconclusive, but some evidence suggests that too much exercise can be harmful.

The researchers were surprised by the large negative effect on lifespan associated with volleyball in both sexes and with handball in men. “We hypothesize,” they write, “that the physical trauma that volleyball players are exposed to [3] may instigate severe skeletomuscular stress, which impacts healthspan, and, in the long term, lifespan.”

In summary, this study established an association between various types of sports and the lifespan of a diverse cohort of international athletes. The impact on lifespan varies across sports, with notable differences between male and female athletes. While male athletes experienced a mostly favorable lifespan extension, with an increment of up to 8 years across different sports, female athletes had limited and scarce data, thus limiting our ability to draw definitive conclusions regarding this association.

Literature

[1] Altulea, A., Rutten, M. G., Verdijk, L. B., & Demaria, M. (2024). Sport and longevity: an observational study of international athletes. GeroScience, 1-13.

[2] Patel, H., Alkhawam, H., Madanieh, R., Shah, N., Kosmas, C. E., & Vittorio, T. J. (2017). Aerobic vs anaerobic exercise training effects on the cardiovascular system. World journal of cardiology, 9(2), 134.

[3] Reitmayer, H. E. (2017). A review on volleyball injuries. Timisoara Physical Education and Rehabilitation Journal, 10(19), 189-194.

The longevity advocacy and lobbying group has submitted detailed feedback to the congressional proposal to replace NIA with the National Institute on Dementia – and now you can sign the petition.

No, dementia doesn’t equal aging

Back in June, the longevity community was rattled by the news that representative Cathy McMorris-Rogers (R-WA), Chair of the Energy and Commerce Committee, proposed a transformation of the National Institute on Aging (NIA) into the National Institute on Dementia. While the proposal, part of a sprawling reform of the National Institutes of Health (NIH), simultaneously called for increasing the institute’s budget by 47 million dollars, it was slammed as misguided and dangerous by many aging experts.

Dementia, of course, is just one age-related disease. Others include cancer, cardiovascular diseases, type 2 diabetes, osteoporosis and osteoarthritis, and so on. The geroscience hypothesis postulates that by influencing common upstream causes of those diseases, such as age-related inflammation (“inflammaging”), immunosenescence, and epigenetic dysregulation, we can exert a much larger effect on healthspan and lifespan than by fighting diseases one by one as they appear.

Cramming the vast realm of aging into the confines of a single age-related disease reveals a fundamental lack of understanding of what aging is and how it relates to human health. Were this proposal to go through, it would cripple aging research.

One of its critics, longevity advocate and author Andrew Steele, quipped on X: “This would be a health research disaster—aging causes 85% of American deaths, but we wouldn’t have an NIH institute?!”

NILAR: a vision for the future

The committee asked the public to submit feedback on the proposal. One organization that answered the call was the Alliance for Longevity Initiatives (A4LI), a DC-based non-profit focused on lobbying and educating politicians on the topic of longevity. A4LI was instrumental in the creation of the congressional Caucus for Longevity Research and has organized numerous high-profile events.

Going beyond critique of the E&C committee’s proposal, A4LI put together its own counterproposal calling for the creation of NILAR: a new National Institute for Longevity and Aging Research. In stark contrast to the committee’s proposal, the one by A4LI is crafted with deep knowledge of the longevity field. It identifies NIH’s lack of focus on longevity research and calls it “a profound misallocation of federal resources.”

“Today, less than 0.5% of NIH funding is allocated toward investigating and treating the biology of aging, despite the fact that biological aging is the primary risk factor for 9 out of 10 leading causes of death in the U.S.,” the proposal says.

The proposed list of NILAR divisions is impressive: Aging Biology; Biomarkers of Health, Function and Aging; Translational Geroscience; and Economic and Societal Impact of Aging. All of these correspond to central problems and subfields in aging research.

“As the urgency of our aging population crisis grows day by day,” the proposal concludes, “the time has come for Congress to establish an agency focused directly on researching and developing therapeutics that target the biology of aging to ameliorate multiple age-related diseases at once.”

Sign to move forward

A4LI also started a petition that you can sign here. It was already signed by about 700 influential academics, biotech executives, and policy leaders. “We aim to reach 1,000 signatures by the end of the year,” A4LI founder Dylan Livingston told Lifespan.io.

“When I started A4LI in early 2021,” he added, “my first priority was to speak with as many industry experts as possible to identify the most critical policy initiatives. Refocusing and increasing funding for aging biology research and development emerged as the top priority. NILAR is the first step toward making that a reality.”

Lifespan.io President Keith Comito assisted with the creation of the proposal in his role as an A4LI board member and was one of the initial group of signatories. While Keith unequivocally supports the NILAR proposal, he has thoughts on how to upgrade it.

“Rather than the agency only passively receiving grant submissions to general grant calls, it would benefit from being more targeted and prescriptive, upregulating certain areas of funding based on tactical analysis of the field,” he said. “This could be assisted by leveraging a network or council of top-class experts with diverse opinions in a model akin to bounties in IT. Instead of just a grant call looking to fund dementia-related therapies, for example, the grant call could already have a very specifically identified research target.” The well-defined NILAR proposal has a context-independent value and can inform any future administration, regardless of the results of the November elections.

“Next, we’ll monitor the upcoming E&C proposal,” Dylan said. “Given the political developments since June 14th, when the E&C Committee first proposed this, I wouldn’t be surprised if we don’t hear anything until after the election. My hope is that NILAR is included in the next proposal, but if not, we have a strong foundation to build on.”

New research in Aging Cell has suggested that targeting senescent cells based on their surface proteins (surfaceome) may be effective in dealing with them.

Focusing on what’s easiest to target

Senescence and the SASP have well-known markers, such as p16, p21, and the well-known SA-β-gal [1]. However, these markers are not particularly specific. Examination of the proteins (proteome) and RNA transcriptions (transcriptome) of these cells provides more information, but that information is not readily available from the surfaces of living cells, which provide the targets of potential drugs.

While previous research has found some molecules that become more common on cells’ surfaces as they become senescent [2, 3, 4], including PD-L2, which helps cells evade the immune system [5], it has proven difficult to translate this basic science into applied biotechnologies. These researchers, therefore, sought to create a more detailed map of the surfaceome, specifically looking for compounds that appear in considerably greater numbers on senescent cells and are feasible to target with drugs.

Different cells give different results

This study was conducted on four different cell types: human lung fibroblasts (NHLFs) and umbilical cord cells (HUVECs) along with astrocytes (ASTs) and embryonic fibroblasts (MEFs) taken from mice. Multiple methods were used to induce senescence, including genotoxins, oxidative stress, and proteosome-related stress, although not all methods were used for all cells. These inducers had mostly expected effects, upregulating well-known inflammatory SASP chemokines.

The differences in method and in cell type drastically affected the surfaceomes of the induced senescent cells. Cells that were exposed to oxidative stress had transporter-related changes, while other cells had changes relating to cell adhesion. Among the three combinations of human cell types and senescence inducements that were used, only 27 surface molecules out of hundreds were changed in common between them, and among the five combinations used for the mouse cells, there was only a single one: N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase (AGA).

Cell type mattered more than the choice of senesence inducer, and the effects on human cells were much greater than on murine cells. Cell type even sometimes reversed the direction of the change in proteins (from 20% to 40% in the three head-to-head comparisons used), even when the inducer was the same. However, this also allowed these researchers to develop signatures: by examining populations of cells, researchers are able to predict what sort of stress brought them to senescence, whether through DNA damage, oxidative stress, or proteasome interference.

Towards new senotherapeutics

This information was put to use in looking for potential new drugs. Four of these proteins, PLXNA1, PLXNA3, PTK7, and CYB5R1, were found to be almost nonexistent outside of senescence and common among various populations of senescent cells, making them prime candidates for senotherapeutic targeting. Examination of 3-month-old and 20-month-old mice found that these proteins do indeed form on the surfaces of naturally senescent cells. Similarly, examining an established dataset found that expression of these proteins coincided with the well-known senescence marker p16ink4a.

These surfaceome markers are already associated with cancer. In fact, targeting PTK7 is already being explored as a cancer therapy [6]. Therapeutics that affect these surface markers, therefore, might be effective in handling some forms of both senescence and cancer: two age-related problems that are sometimes in opposition and sometimes coincide.

Literature

[1] Demaria, H. S. A. N. J. M.(2018). Hallmarks of Cellular Senescence. Trends Cel. Biol, 28, 436-453.

[2] Kim, K. M., Noh, J. H., Bodogai, M., Martindale, J. L., Pandey, P. R., Yang, X., … & Gorospe, M. (2018). SCAMP4 enhances the senescent cell secretome. Genes & development, 32(13-14), 909-914.

[3] Kim, K. M., Noh, J. H., Bodogai, M., Martindale, J. L., Yang, X., Indig, F. E., … & Gorospe, M. (2017). Identification of senescent cell surface targetable protein DPP4. Genes & development, 31(15), 1529-1534.

[4] Mrazkova, B., Dzijak, R., Imrichova, T., Kyjacova, L., Barath, P., Dzubak, P., … & Hodny, Z. (2018). Induction, regulation and roles of neural adhesion molecule L1CAM in cellular senescence. Aging (Albany NY), 10(3), 434.

[5] Chaib, S., López-Domínguez, J. A., Lalinde-Gutiérrez, M., Prats, N., Marin, I., Boix, O., … & Serrano, M. (2024). The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2. Nature cancer, 5(3), 448-462.

[6] Jie, Y., Liu, G., Feng, L., Li, Y., E, M., Wu, L., … & Gu, A. (2021). PTK7-targeting CAR T-cells for the treatment of lung cancer and other malignancies. Frontiers in Immunology, 12, 665970.