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Grape seed chemical allows mice to live longer by killing aged cells

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A chemical derived from grape seeds selectively destroys worn-out cells in mice, allowing them to live 9 per cent longer than their untreated counterparts



Health



6 December 2021

Grapes cut open to reveal their seeds

Shutterstock / kholywood

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A chemical isolated from grape seed extract prolongs the lifespans of old mice by 9 per cent by clearing out their old, worn-out cells. The treatment also seems to make the mice physically fitter and reduces the size of tumours when used alongside chemotherapy to treat cancer.

The finding strengthens the case for future anti-ageing therapies that target senescent cells – aged cells that lose their ability to replicate and instead churn out substances that cause inflammation.

Senescent cells increase in number as we get older, and have been linked to various age-related conditions, including cardiovascular disease, type 2 diabetes and osteoporosis.

To find a substance that might destroy these cells, Qixia Xu at the University of Chinese Academy of Sciences in Shanghai and colleagues screened a library of chemicals linked to ageing for their effects against senescent cells. The team’s search turned up a chemical found in grape seeds called procyanidin C1 (PCC1).

At low concentrations, PCC1 appeared to prevent senescent cells in a dish from producing inflammatory substances. At high concentrations, the chemical killed the cells, while leaving younger cells intact.

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To test its effectiveness in living animals, the team injected 171 mice that were 2 years old – equivalent to around 70 in human years – with either PCC1 or a control solution twice a week for the rest of the animals’ lives. On average, PCC1 increased the lifespan of mice by 9 per cent.

The chemical also appears to improve the physical fitness of younger mice. Animals under the age of 2 years were injected with either a control solution or PCC1 every two weeks for four months, after which they underwent a range of physical tests. Mice that received the treatment had a significantly faster maximum walking speed, stronger grip strength and better endurance when running on a treadmill, compared with mice that had been given the control solution.

Chemotherapy is known to accelerate the ageing of cells within tumours. To find out if PCC1 could kill these aged tumour cells, boosting the impact of chemotherapy, the team trialled the chemical alongside mitoxantrone, a drug used to treat breast cancer, non-Hodgkin lymphoma and acute myeloblastic leukaemia, among other cancers.

The team tested this combination treatment in mice implanted with cells from human prostate tumours. Treating mice with both PCC1 and mitoxantrone shrank tumours by around 75 per cent, whereas chemotherapy alone reduced them by 44 per cent, on average.

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The fact that the chemical didn’t seem to affect healthy cells suggests it could be “a promising anti-ageing therapeutic treatment”, says Dorian Ziegler at the University of Lausanne in Switzerland. Future research will need to investigate whether PCC1 has similar effects on people, he adds.

Journal reference: Nature Metabolism, DOI: 10.1038/s42255-021-00491-8

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