How To Fine-Tune Bacterial Metabolism To Boost Longevity

Studies have shown that gut microbes can influence several aspects of the host’s life, including aging. Given the complexity and heterogeneity of the human gut environment, elucidating how a specific microbial species contributes to longevity has been challenging.

To explore the influence of bacterial products on the aging process, scientists at Baylor College of Medicine and Rice University developed a method that uses light to directly control gene expression and metabolite production from bacteria residing in the gut of the laboratory worm Caenorhabditis elegans.

The team reports (“Optogenetic control of gut bacterial metabolism to promote longevity”) in eLife that green-light-induced production of colanic acid by resident Escherichia coli bacteria protected gut cells against stress-induced cellular damage and extended the worm’s lifespan. The researchers indicate that this method can be applied to study other bacteria and propose that it also might provide in the future a new way to fine-tune bacterial metabolism in the host gut to deliver health benefits with minimal side effects.

Illustration of bacteria in the intestine.

Gut microbial metabolism is associated with host longevity. However, because it requires direct manipulation of microbial metabolism in situ, establishing a causal link between these two processes remains challenging. We demonstrate an optogenetic method to control gene expression and metabolite production from bacteria residing in the host gut. We genetically engineer an E. coli strain that secretes colanic acid (CA) under the quantitative control of light,” the investigators wrote.

Using this optogenetically-controlled strain to induce CA production directly in the C. elegans gut, we reveal the local effect of CA in protecting intestinal mitochondria from stress-induced hyper-fragmentation. We also demonstrate that the lifespan-extending effect of this strain is positively correlated with the intensity of green light, indicating a dose-dependent CA benefit on the host.

“Thus, optogenetics can be used to achieve quantitative and temporal control of [the microbiome] metabolism in order to reveal its local and systemic effects on host health and aging. “We used optogenetics, a method that combines light and genetically engineered light-sensitive proteins to regulate molecular events in a targeted manner in living cells or organisms,” said co-corresponding author Meng Wang, PhD, professor of molecular and human genetics at the Huffington Center on Aging at Baylor.

Source: https://www.genengnews.com/

Blood Iron Levels Are Key To Slowing Ageing

Genes that could help explain why some people age at different rates to others have been identified by scientists. The international study using genetic data from more than a million people suggests that maintaining healthy levels of iron in the blood could be a key to ageing better and living longer. The findings could accelerate the development of drugs to reduce age-related diseases, extend healthy years of life and increase the chances of living to old age free of disease, the researchers say.

Scientists from the University of Edinburgh and the Max Planck Institute for Biology of Ageing in Germany focused on three measures linked to biological ageinglifespan, years of life lived free of disease (healthspan), and being extremely long–lived (longevity). Biological ageing – the rate at which our bodies decline over time – varies between people and drives the world’s most fatal diseases, including heart disease, dementia and cancers. The researchers pooled information from three public datasets to enable an analysis in unprecedented detail. The combined dataset was equivalent to studying 1.75 million lifespans or more than 60,000 extremely long-lived people. The team pinpointed ten regions of the genome linked to long lifespan, healthspan and longevity. They also found that gene sets linked to iron were overrepresented in their analysis of all three measures of ageing. The researchers confirmed this using a statistical method – known as Mendelian randomisation – that suggested that genes involved in metabolising iron in the blood are partly responsible for a healthy long life.

Blood iron is affected by diet and abnormally high or low levels are linked to age-related conditions such as Parkinson’s disease, liver disease and a decline in the body’s ability to fight infection in older age. The researchers say that designing a drug that could mimic the influence of genetic variation on iron metabolism could be a future step to overcome some of the effects of ageing, but caution that more work is required.

Anonymised datasets linking genetic variation to healthspan, lifespan, and longevity were downloaded from the publicly available Zenodo, Edinburgh DataShare and Longevity Genomics servers.

We are very excited by these findings as they strongly suggest that high levels of iron in the blood reduces our healthy years of life, and keeping these levels in check could prevent age-related damage. We speculate that our findings on iron metabolism might also start to explain why very high levels of iron-rich red meat in the diet has been linked to age-related conditions such as heart disease”, said Dr Paul Timmers from the Usher Institute.

The study was funded by the Medical Research Council and is published in the journal Nature Communications.

Source: https://www.ed.ac.uk/