LongeCityNews Last Updated: 02 April 2026 - 04:02 PM

Cartilage is one of the least regenerative tissues in the body, and thus damage and aging leads to osteoarthritis, disability, and joint pain. There is considerable interest in finding ways to effectively repair or replace cartilage, provoke existing tissue into greater regenerative capacity, or adjust cellular biochemistry to make cartilage more resilient to damage and cell death. Here, researchers report on the manipulation of a regulatory protein in cartilage cells, NR0B2, also known as SHP, that is reduced in expression as osteoarthritis progresses, and appears to be protective. It might prove to be a useful target to slow the progression of cartilage loss and osteoarthritis.

Osteoarthritis (OA), characterised by cartilage destruction, is the most common degenerative joint disease. However, no effective disease-modifying OA therapy is currently available. Herein, we report orphan nuclear receptor small heterodimer partner (SHP, NR0B2) as a novel catabolic regulator of OA pathogenesis. NR0B2 expression was markedly downregulated in cartilage from patients with OA.

Global or chondrocyte-specific Nr0b2 deletion in male mice exacerbated OA-related pain and structural changes following surgical destabilization of the medial meniscus, accompanied by increased matrix metalloproteinase (MMP)-3 and MMP-13 expression in chondrocytes. Conversely, adeno-associated virus-mediated Nr0b2 overexpression in knee joints of male mice protected against accelerated knee OA caused by Nr0b2 deficiency. Mechanistically, NR0B2 inhibited IKKβ kinase activity via IKK complex interaction, downregulating NF-κB signalling.

Our results demonstrate that NR0B2 has a chondroprotective role in OA progression by regulating matrix-degrading enzymes in an IKKβ/NF-κB-dependent manner, and gene therapy targeting Nr0b2 may be a promising therapeutic strategy for OA.

Link: https://doi.org/10.1038/s41467-026-69864-5

A range of evidence suggests that severe infection causes lasting damage that accelerates degenerative aging. That damage includes an increased burden of senescent cells and their inflammatory signaling, and changes to the immune system that reduce capacity and increase chronic inflammation. Here, researchers process epidemiological data to show that weathering a severe infection is associated with an increased risk of later dementia. Neurodegeneration is accelerated by the chronic inflammation of aging, as are most of the common, ultimately fatal age-related diseases. Unresolved, constant inflammatory signaling is disruptive to tissue structure and function.

Severe infections have been linked to an increased risk of dementia, but both conditions often coexist with other illnesses that may confound this association. Using nationwide Finnish health registry data, we examined the role of noninfectious mental and physical illnesses in the association between severe infections and dementia. This register-based study included 62,555 individuals aged 65 or older in Finland in 2016 who were diagnosed with late-onset dementia between 2017 and 2020 and 312,772 dementia-free controls matched for year of birth, sex, and the follow-up period. Analyses were adjusted for education, marital status, employment, and area of residence, with age and sex accounted for through the matched conditional design and analysis.

Applying a 1-year lag period, we identified 29 hospital-treated diseases that occurred 1-21 years before dementia diagnosis in cases (or index date in controls), had a prevalence of ≥ 1% prior to dementia, and were robustly associated with increased dementia risk (confounder-adjusted rate ratio ≥ 1.20). In addition to 2 infectious diseases (cystitis and bacterial infection of an unspecified site), these included 27 mental, behavioural, digestive, endocrine, cardiometabolic, neurological, and eye diseases, as well as injuries. 29,376 (47%) of the dementia cases had at least one of these diseases diagnosed before dementia.

The associations between the two infectious diseases and dementia risk were not attributable to the 27 comorbid dementia-related diseases diagnosed before infections. The adjusted rate ratio for cystitis was 1.22 before and 1.19 after adjustment for comorbidities, while for bacterial infections of an unspecified site, the rate ratios were 1.21 and 1.19, respectively. The findings were comparable across subgroups defined by sex and education, and stronger for cases of early onset dementia.

Link: https://doi.org/10.1371/journal.pmed.1004688

A recent study suggests that the transition of king penguins from the wild to a zoo environment, which resembles a sedentary, well-fed Western lifestyle, results in accelerated aging and changes in metabolic pathways [1].

A unique model system

A sedentary lifestyle and obesity are linked to accelerated aging in humans and, at the molecular level, negatively impact the hallmarks of aging [2, 3]. On the other hand, such interventions as increasing physical activity [4], caloric restriction [5], and manipulation of nutrient-sensing pathways [6] are reported to have a positive impact on the rate of aging. However, much of the data on this topic comes from mouse models, which have limitations, and whether these findings will translate to humans and provide lifelong improvements remains debated [7], creating the need for alternative model systems.

A team of researchers based in Europe decided to explore this research area using king penguins. King penguins, when living in the wild, show a unique behavior among model systems studied to date: voluntary fasting. Specifically, during their breeding cycle, king penguins undergo prolonged fasting periods (up to 8 weeks) that have been shown to involve physiological traits similar to those observed in human fasting [8]. These fasting periods are followed by periods of extreme physical activity.

While penguins are not the kind of animals routinely kept in labs, they are frequent inhabitants of zoos around the world, where researchers can study them. When penguins are moved from the wild to the zoo, the transition resembles a shift to a Western lifestyle in humans: their physical activity levels decline, and animals frequently become overweight. [9] This kind of lifestyle change creates a unique opportunity for experimentation, in which the wild environment, with high levels of physical activity and voluntary caloric restriction, serves as the control state, while the zoo environment, with continuous feeding and sedentary behavior resembling the Western lifestyle, is treated as the experimental manipulation. The researchers hypothesized that such a Western-style environment would accelerate aging in zoo-housed king penguins.

“We wanted to investigate whether turning these penguins into nonchalant, well-fed, and well-cared-for individuals would alter their aging trajectory. Since this lifestyle already occurs in zoos, the setup was ideal,” said Robin Cristofari from the University of Helsinki, first author of the study.

Faster aging but longer lives

To estimate penguins’ biological age, the researchers relied on a penguin genome-adapted methylation-based epigenetic clock, as is commonly done in other species and humans. The results showed that zoo-housed king penguins exhibit accelerated epigenetic aging compared with age-matched penguins living in the wild. The numerical value of the acceleration varied between different modeling approaches but was estimated to be between around 2.5 and 6.5 years. Such age acceleration is comparable (when adjusted for the penguin’s lifespan) to the differences seen between smokers and non-smokers in humans.

This accelerated epigenetic aging didn’t translate to faster death. The researchers reported that the median survival age was almost 21 years for zoo-housed penguins and 13.5 years for those in the wild. Those differences are caused by high mortality among young penguins in the wild and zoo animals being protected from predators and having an abundance of food and medical care that allows them to live longer.

“A 15-year-old penguin in the zoo has the body of a 20-year-old penguin in the wild. However, the interesting part is that zoo penguins also live longer, overall. They may be less physically fit, but with no natural predators or Antarctic storms to contend with and with access to veterinary care, they can survive long past the age at which they would typically die in the Southern Ocean,” explains co-researcher Céline Le Bohec, from the French CNRS. This data suggests that the Western lifestyle might increase lifespan but not healthspan, which is in line with observations in humans.

Metabolic changes

To understand age acceleration in the zoo environment, the researchers searched for differences in methylation patterns between the two groups, identifying nearly 300 genes clustered into 11 different molecular pathways. Those pathways were involved in cell growth and in linking nutrient sensing to aging and age acceleration, all supporting the hypothesis that a Western-like sedentary, well-fed lifestyle influences core metabolic processes in king penguins.

Further analysis of the specific genes identified in this study emphasizes their impact on metabolism. For example, a few identified genes are known to play a role in coping with excessive nutrient intake, while others were linked to heart function and physical activity.

The researchers report that their results suggest that zoo-housed penguins need to make significant changes in their gene expression and metabolism to compensate for shifts in diet, especially in lipid composition and food abundance, compared with their wild diet. Additional epigenetic changes are also caused by the substantial decrease in physical activity

Finding a balance

This study adds additional data supporting the detrimental role of a sedentary lifestyle combined with abundant food in age acceleration, a phenomenon that appears to be conserved across various animal species. What’s more, the conclusions drawn from these observations suggest that age acceleration results from the suppression of physical activity and periodic caloric restriction, rather than from being overweight, as the penguins in this study were not clinically obese.

The researchers plan to continue this research in the hope of identifying a lifestyle that can extend both lifespan and healthspan. “We are currently conducting a study in which we induce penguins to eat less and exercise more. It is important to find a moderate lifestyle in a world of abundance—for us humans as well,” concluded research curator Leyla Davis from Zoo Zurich.

Literature

[1] Cristofari, R., Davis, L. R., Bardon, G., Nitta Fernandes, F. A., Figueroa, M. E., Franzenburg, S., Gauthier-Clerc, M., Grande, F., Heidrich, R., Hukkanen, M., Le Maho, Y., Ollikainen, M., Paciello, E., Rampal, P., Stenseth, N. C., Trucchi, E., Zahn, S., Le Bohec, C., & Meyer, B. S. (2026). Lifestyle change accelerates epigenetic ageing in King penguins. Nature communications, 10.1038/s41467-026-70527-8. Advance online publication.

[2] de Rezende, L. F., Rey-López, J. P., Matsudo, V. K., & do Carmo Luiz, O. (2014). Sedentary behavior and health outcomes among older adults: a systematic review. BMC public health, 14, 333.

[3] Tam, B. T., Morais, J. A., & Santosa, S. (2020). Obesity and ageing: Two sides of the same coin. Obesity reviews : an official journal of the International Association for the Study of Obesity, 21(4), e12991.

[4] Ekelund, U., Steene-Johannessen, J., Brown, W. J., Fagerland, M. W., Owen, N., Powell, K. E., Bauman, A., Lee, I. M., Lancet Physical Activity Series 2 Executive Committe, & Lancet Sedentary Behaviour Working Group (2016). Does physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonised meta-analysis of data from more than 1 million men and women. Lancet (London, England), 388(10051), 1302–1310.

[5] Maegawa, S., Lu, Y., Tahara, T., Lee, J. T., Madzo, J., Liang, S., Jelinek, J., Colman, R. J., & Issa, J. J. (2017). Caloric restriction delays age-related methylation drift. Nature communications, 8(1), 539.

[6] Madeo, F., Pietrocola, F., Eisenberg, T., & Kroemer, G. (2014). Caloric restriction mimetics: towards a molecular definition. Nature reviews. Drug discovery, 13(10), 727–740.

[7] Phelan, J. P., & Rose, M. R. (2005). Why dietary restriction substantially increases longevity in animal models but won’t in humans. Ageing research reviews, 4(3), 339–350.

[8] Groscolas, R., & Robin, J. P. (2001). Long-term fasting and re-feeding in penguins. Comparative biochemistry and physiology. Part A, Molecular & integrative physiology, 128(3), 645–655.

[9] Fens, A., & Clauss, M. (2024). Nutrition as an integral part of behavioural management of zoo animals. Journal of Zoo and Aquarium Research, 12(4), Epub ahead of print.

Animal studies show that ascending doses of nanoplastic particle infiltration into tissues eventually rise to the level of inducing dysfunction. Evidently harmful nanoplastic exposure doses are considerably higher than what are thought to be environmental exposure doses in the wild at the present time, but equally it is challenging, costly, and takes a long time to build a body of literature focused on subtle effects that may only emerge over the long term to affect the pace of aging. This is a work in progress.

The difference between nanoplastics and particulate air pollution is that there is a very large body of evidence to quantify the harms done by exposure to air pollution in human populations, alongside convincing mechanistic studies to show how long-term health and pace of aging can be negatively impacted. That body of evidence has yet to be constructed for nanoplastic exposure in human populations, so while there is a great deal of concern around this topic, it is unclear as to how much of that concern is justified. The level of interest in the topic means that the necessary epidemiological and supporting mechanistic data, analogous to the existing body of work covering air pollution, will almost certainly be produced in the years ahead, however.

Micro- and Nanoplastics Exposure Across the Lifespan: One Health Implications for Aging and Longevity

Microplastics and nanoplastics (MNPs) are pervasive environmental contaminants with growing relevance for human health across the lifespan. Older adults may be especially vulnerable to their effects due to cumulative lifetime exposure, age-related physiological changes, and a higher burden of chronic disease. Adopting a One Health perspective, this review synthesizes current evidence on the sources, exposure pathways, and biological effects of MNPs, integrating findings from environmental, animal, and human studies with a specific focus on aging populations.

Experimental studies consistently show that MNP exposure triggers oxidative stress, inflammation, mitochondrial dysfunction, and cellular senescence, mechanisms central to biological aging. These processes are linked to dysfunction of the cardiovascular, nervous, gastrointestinal, and immune systems, suggesting that MNPs may contribute to the development or progression of age-related diseases. Within the One Health framework, MNPs also act as carriers of chemical additives and environmental pollutants, potentially amplifying health risks through combined and cumulative exposures along food chains and ecosystems.

Despite increasing mechanistic evidence, direct epidemiological data in older adults remain limited. This review highlights key knowledge gaps and emphasizes the need for integrative, longitudinal research to clarify the role of MNPs in aging and to inform public health and environmental policy.