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Study Finds Antioxidants Extend Nematode Lifespan Differently by Species

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A recent study by the Caenorhabditis Intervention Testing Program (CITP) has found that the antioxidants green tea extract (GTE) and nordihydroguaiaretic acid (NDGA) can extend lifespan in certain species of nematodes, though the effects vary significantly across different genetic backgrounds. This research underscores the complexity of evaluating ageing interventions and the necessity for genetic diversity in testing. The findings were published in the journal GeroScience.

The CITP, funded by the NIH, is a collaborative effort among three independent research institutions: Rutgers University, the University of Oregon, and the Buck Institute for Research on Aging. The programme aims to identify chemical interventions that reliably promote health and longevity across a genetically diverse array of Caenorhabditis species and strains.

This study focused on five compounds previously shown to affect lifespan in various organisms: 17α-estradiol, acarbose, green tea extract, nordihydroguaiaretic acid, and rapamycin. The researchers utilised both manual lifespan assays and automated Lifespan Machines (ALMs) to measure the effects of these compounds on nematode lifespan and healthspan.

The study found that GTE and NDGA were the most effective in extending lifespan, though the effects were highly species-specific. GTE extended the lifespan in two species: Caenorhabditis elegans and Caenorhabditis tropicalis. In C. elegans, two out of three strains showed a lifespan increase of more than 15% when treated with GTE, while all three tested strains of C. tropicalis displayed a small but significant increase in lifespan.

NDGA also showed species-specific effects, with the most pronounced lifespan extension observed in C. briggsae. Interestingly, the research revealed that the method of lifespan determination (manual vs. automated) could yield different outcomes, highlighting the importance of experimental protocol in such studies. For instance, NDGA increased the lifespan in C. briggsae strains using ALMs, but manual assays indicated decreased survival in certain genetic backgrounds.

In addition to lifespan, the study examined healthspan measures such as swimming ability and resistance to oxidative stress. The results showed that GTE and NDGA had strain-specific impacts on these health measures. For example, GTE reduced oxidative stress resistance in most C. briggsae strains, indicating a potential anti-hormetic effect. But C. tropicalis JU1373 showed an age-dependent increase in oxidative stress survival with GTE treatment.

Swimming ability, a measure of locomotory health, was also affected by the compounds. GTE and NDGA showed strain-specific effects on swimming ability, with some strains exhibiting improved locomotion and others showing no significant change. This variability underscores the disconnect between longevity and certain health measures.

The findings from this study highlight the challenges in translating results from model organisms to broader applications, such as human aging interventions. The genetic background of the test subjects plays a crucial role in the efficacy of the interventions, suggesting that compounds that work across a wide range of genetic backgrounds may be rare but valuable for further testing in mammalian models.

The CITP’s approach of using a genetically diverse panel of Caenorhabditis species provides a robust framework for identifying potential ageing interventions. Future research will continue to refine these methods and explore additional compounds that could extend healthspan and lifespan in a consistent manner across different genetic backgrounds.

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