As we age, our body loses its ability to clear out zombie-like cells that have stopped dividing, instead dripping out poison and turning other cells rogue. Restoring the ability to remove these 鈥渟enescent鈥� cells prevented signs of cognitive decline and frailty in older mice, with hints that the same outcomes could occur in people.

鈥淲hat鈥檚 attractive about this study is that it is not trying to kill [senescent] cells directly,鈥� says at University College London, who wasn鈥檛 involved in the research. 鈥淚t is repairing the body鈥檚 own waste-disposal system that should have removed them in the first place.鈥�

To better understand why this system goes awry, at Stanford University, California, and her colleagues compared mice aged 6 to 8 months (roughly equivalent to people in their 20s) with mice aged 23 to 25 months (equivalent to people in their late 60s or 70s). They found that the older mice had more of these senescent cells in their organs, including the liver and spleen, as well as in their bone marrow.

Specifically, the senescent cells were neutrophils, immune cells that are normally the body鈥檚 first line of defence against infection. These would normally be cleared away by macrophages residing in tissue, which remove damaged cells and debris, but this ability .

Andreasson and her colleagues traced this decline to prostaglandin E2, a signalling molecule that increases with age. They found that higher prostaglandin E2 activity overstimulates a receptor called EP2 on tissue-resident macrophages, which leaves them less able to remove senescent cells.

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Next, the team tested whether blocking this overstimulation could improve signs of ageing by genetically modifying the EP2 gene from tissue-resident macrophages in older mice. These animals went on to clear more senescent neutrophils and showed signs of healthier ageing, including lower levels of inflammation, reduced muscle loss, less visceral fat and better mobility, compared with unmodified mice of the same age. They also performed almost as well as young mice in memory tests.

鈥淲e were very surprised at the magnitude of the effect,鈥� says Andreasson. 鈥淭he paradox is that we had only reduced the level of [the receptor protein] EP2 by 50 per cent.鈥�

The researchers also tested an experimental drug that blocks the EP2 receptor protein. When given orally to older mice for two months, this caused similar age-related improvements to those experienced by the genetically modified mice.

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鈥淭his is a very promising study, but we need to be careful,鈥� says Gilroy. 鈥淸The聽EP2 receptor]聽is part of a normal signalling system, and blocking it throughout the body could have unwanted effects.鈥� The mice experienced no known side effects, but Gilroy says it may be safer to target the EP2 receptor in ageing macrophages specifically.

Finally, the team found similar patterns in human tissue, with liver samples from older people showing higher EP2 receptor activity and more senescent neutrophils. 鈥淭he human data are supportive, but still correlative,鈥� says Gilroy. 鈥淲e haven鈥檛 yet shown that blocking [the EP2 receptor] can restore neutrophil clearance in aged human tissue.鈥澛�

The researchers are now planning to study whether this process affects the onset of conditions such as Alzheimer鈥檚 disease.

A living organism is made from components that aren鈥檛 themselves living. This simple statement has profound implications. For one, it means that there is no mystical force that animates us and other life forms. For another, it means that it should be possible to build a life form from scratch 鈥� and we are now a step closer to doing so.

Artificial life has been the guiding light of synthetic biology for some time. In 2010, biologists at the J. Craig Venter Institute in California synthesised the stripped-down genome of a bacterium and inserted it into the chassis of another cell, emptied of its own DNA. The resulting organism, with a record-low number of genes (473) was able to grow and reproduce. But even then, scientists didn鈥檛 understand what a third of those genes were doing, or whether they were even needed. Instead of rebooting an existing cell with a synthetic genome, we need to build an organism from the ground up.

That is what scientists at the University of Missouri are now attempting. The SpudCell 鈥� named both to evoke Sputnik and the dawn of the space age, and for its resemblance to a potato 鈥� is an entity based on just 36 genes. It self-assembled when the genes were supplied with all the building blocks necessary for life, forming cell-like bubbles and making proteins.

SpudCell represents a significant breakthrough in the creation of artificial life

But that鈥檚 it. The SpudCell can only make proteins because it is supplied with ribosomes, the crucial cell components that make proteins. It can鈥檛 metabolise food, supply itself with energy or reliably divide and reproduce. It isn鈥檛 alive, and it needs intensive care just to perform its basic functions. Nevertheless, the SpudCell represents a significant breakthrough in the creation of artificial life. If a modern living cell is a jet airliner, the SpudCell is the rickety wooden-and-cotton proto-airplane made by the Wright brothers.

Better versions will soon follow, with potentially transformative applications. The hope is that synthetic cells will one day be able to supply materials that are currently derived from fossil fuels, such as plastics, fuels and fertiliser. That is keenly needed. But the work in understanding how a living entity operates will shed light on what life needs, and how it emerges from dead materials. If we crack this ultimate mystery, synthetic biology will have really delivered.

The 鈥淪pudCell鈥� is being proclaimed by its creators as a major advance in synthetic biology. Some of this hype is justified 鈥� yes, it鈥檚 a cell, but perhaps not quite what you could call a living cell. It has 36 genes that allow it to copy DNA and replicate in a primitive way, but it needs a lot of outside help and fails after five or so divisions. That is, however, much more than any other team has achieved, so it is arguably the greatest feat of bioengineering to date.

Created by at the University of Minnesota and her colleagues, the team is now making the SpudCell project open source so it can be developed further and even made capable of dividing indefinitely. Here鈥檚 what you need to know:

What is the SpudCell?

It鈥檚 a step towards creating a minimal life form whose functions are fully understood. Previous attempts involved deleting genes from bacterial cells whose genomes are small to start with. For instance, in 2016, a bacterium with 901 genes was stripped down so it had just 473 genes. Adamala鈥檚 team did things the other way round, starting with just 36 genes. These mostly come from E. coli bacteria, but there are also some from phage viruses that infect bacteria and one for a fluorescent protein from jellyfish to help make the cells visible.

So, is it alive?

No. It can do some of the things that living cells do, such as replicating its genes and dividing, but it doesn鈥檛 do them well and it needs a lot of outside help just to do them badly. For instance, the researchers have demonstrated evolution in the sense that when they introduced a beneficial mutation, those cells did better. But the mutation had to be introduced deliberately rather than occurring spontaneously. 鈥淚 think I would be satisfied with calling it living if it鈥檚 replicating indefinitely and if it鈥檚 capable of Darwinian evolution,鈥� says Adamala.

Can we really call it a synthetic cell, then?

That depends on how you define things. It is a synthetic cell in the sense that it has been put together in a lab and does some of the things a cell does. But it鈥檚 been made using parts of existing cells 鈥� mainly those 36 genes 鈥� rather than being created entirely from scratch. It could be thought of as an extremely stripped-down E. coli bacterium with a few additions from other viruses, bacteria and jellyfish.

How was it assembled?

The researchers engineered the 36 genes into seven circular pieces of DNA. They made lots of copies of them and put them into a solution containing all the other things the cells need, like the building blocks of DNA and proteins, and fatty molecules that spontaneously form cell-like bubbles. Some of these bubbles ended up with all seven parts of the genome.

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The cells are then kept alive by two of the genes coding for proteins that form pores in the membrane, allowing some small molecules to enter. Larger molecules are supplied in the form of small bubbles that fuse with the cells. So the cell is supplied with all the building blocks of life, because it can鈥檛 make any itself.

How do the cells divide?

The team added large proteins to the solution that bind to one of the protein pores that protrude from the membrane. These jostle for space and cause the membrane to bend, says Adamala, which can result in part of the SpudCell budding off and forming a separate bubble of its own. It isn鈥檛 an equal division into two parts, and the resulting 鈥渄aughter鈥� cells have a random selection of the circular bits of DNA, so many lack the full sets of genes.

Why not just put all the genes on one piece of DNA?

This would be better to ensure daughter cells get all of the genes, but it is very hard to work with such large pieces of DNA, says Adamala. 鈥淥nce we have a genome we鈥檙e happy with, it definitely has to go on a single large [piece].鈥�

Why do the cells stop doing anything after about five rounds of division?

The team doesn鈥檛 know for sure, but the cells aren鈥檛 capable of creating their own protein-making factories, or ribosomes. They have to be supplied with them. 鈥淲e鈥檙e speculating that it is because of the failure of the ribosomes [that the cells stop dividing],鈥� says Adamala. So once the cells can make their own ribosomes, they may be able to keep dividing indefinitely. 鈥淚 think it is achievable very soon,鈥� she says.

This is all very impressive, but why create SpudCell in the first place?

鈥淲e want to be able to make all petrochemicals with living biology, so we can basically move away from oil for all the climate and societal benefits,鈥� says Adamala. Virtually all of the chemicals we depend on, from plastics to pesticides, are derived from oil and gas. Many of these chemicals are toxic, she says, and would kill normal cells that made them. But synthetic cells could be designed to tolerate them.

Could it ever be dangerous?

No. It鈥檚 a bed-ridden Frankenstein鈥檚 monster that has to be spoon-fed. There鈥檚 no danger of it running amok. And even if it really can be brought fully to life, it is unlikely to be able to survive outside a lab or factory. Existing bacteria are a far greater threat.

Human eggs seem to dispose of their waste more slowly than other cells do, which may help them avoid wear and tear 鈥� and explain why they live longer.

Every woman is born with a finite number of egg cells, or oocytes, which need to survive for about five decades. For cells, that鈥檚 an unusually long time. Although some human cells, like those in the brain and eyes, can live as long as you do, most have much shorter lifespans, in part because the natural processes that allow them to function also damage them over time.

Cells must recycle their proteins as a form of necessary housekeeping 鈥� but it comes at a cost. The energy consumed in this process can generate molecules called reactive oxygen species, or ROS, which cause random damage in the cell. 鈥淭his is damage happening in the background all the time,鈥� says at Center for Genomic Regulation in Spain. 聽鈥淭he more ROS there is, the more damage there鈥檚 going to be.鈥�

But healthy eggs seem to avoid this issue. To find out why, B枚ke and her colleagues studied harvested human eggs under a microscope. The cells were placed in a liquid with fluorescent dyes, which bind to acidic cellular components, called lysosomes, that behave as 鈥渞ecycling plants鈥�, says at the University of Cologne in Germany.

The bright dye revealed the waste-disposing lysosomes in human eggs were less active than the same components in other human cell types or those in the egg cells of smaller mammals, like mice. Zaffagnini and his colleagues say this may be a form of self preservation.

Slowing down their waste-disposal mechanism may be just one of many ways human egg cells achieve their relatively long lifespans, says Zaffagnini. B枚ke speculates to avoid damage, the human oocytes 鈥減ut a brake on everything鈥�. If all cell processes run slower in human egg cells, she says, this could result in lower levels of harmful ROS, and therefore less risk of damage.

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Since delaying the protein-recycling process seems to help egg cells maintain their health, failing to do so could explain what makes some oocytes unhealthy. 鈥淭he way I see this is, it could be a clue into why human oocytes really become dysfunctional after a certain time,鈥� says at Yale School of Medicine. 鈥淚t could be a segue into advanced assessment of all the things that go wrong in human oocytes,鈥� he says.

Assessing egg health in this way could eventually improve fertility treatments. 鈥淲e do know that protein degradation is essential for cell survival, so it 100 per cent does affect fertility,鈥� says B枚ke. She notes the study focused on healthy eggs; she says work to compare those cells with eggs from people affected by complications with fertility is ongoing. 鈥淚f there鈥檚 high ROS in the cell, there are poor IVF outcomes,鈥� she says.

Human egg cells are still not well understood, because they are difficult to study. 鈥淸They are] hard to work with, because the sample limitation is an issue,鈥� says B枚ke. Seli says this obstacle is one of 鈥渕ultiple layers鈥� to the problem, which also include regulations restricting the study of egg cells and a lack of funding.

If these hurdles can be surpassed, Zaffagnini says, there may be 鈥渞eally surprising鈥� results. 鈥淚t鈥檚 really worth it,鈥� he says.

Whether or not we grow new brain cells as adults has been the subject of an ongoing and often contentious debate. Now, evidence suggests that we can. This could help answer one of neuroscience鈥檚 most controversial questions and has sparked some speculation that the process could be exploited to treat conditions like depression and Alzheimer鈥檚 disease.

New neurons form via a process called neurogenesis in children, as well as in adult and . This involves stem cells repeatedly giving rise to so-called progenitor cells that proliferate to form immature neurons that later become fully developed.

Prior studies on human adults have identified and in the hippocampus. This brain region, which is crucial for learning and memory, is a prime spot for neurogenesis in children and some adult animals, but progenitor cells have yet to be seen here in adult humans. 鈥淲e were missing this link, and that鈥檚 one of the main arguments against new neurons forming in the adult human brain,鈥� says at the Netherlands Institute for Neuroscience, who wasn鈥檛 involved in the new research.

To find this link, at the Karolinska Institute in Sweden and his colleagues first set about creating machine learning models that can accurately identify progenitor cells. This involved collecting hippocampus samples from six young children whose brains were donated by their parents for research when they died.

The researchers trained the artificial intelligence models to identify progenitor cells based on the activity of around 10,000 genes, using data extracted from the samples. 鈥淚n childhood, progenitor cells look similar to what they do in mice, so we can easily identify these,鈥� says Fris茅n. 鈥淸The idea is] we can take the molecular fingerprints of childhood progenitors and use that to identify these cells in adults.鈥�

To put the models to the test, the team had them identify progenitor cells in hippocampus samples from young mice. The models correctly pinpointed 83 per cent of the progenitor cells and incorrectly classed another type of cell as a progenitor less than 1 per cent of the time. In another test, the models correctly predicted an almost complete absence of progenitor cells in samples of an adult human cortex, a brain region where there is no evidence to suggest neurogenesis occurs in people.

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鈥淭hey really nicely validate their model by going from human child data, to mouse data and then adult human data,鈥� says at King鈥檚 College London.

Once this validation was complete, the researchers could test if neurogenesis occurs in human adults, by using the models to pinpoint progenitor cells in the hippocampus of 14 people who were aged between 20 and 78 when they died.

Crucially, they first carried out a step that increased their odds of catching progenitor cells, which The team used an antibody to select for brain cells that were dividing at the time of death, including non-neuronal cells such as immune cells and any progenitors. This helped to exclude common non-dividing neuronal cells, such as mature neurons, making it easier to find rare ones.

They then fed data that related to the genetic activity from those dividing cells into the models. 鈥淭hey enriched for the dividing cells, this allowed them to find those very rare cells which are missed if you put all the cells in,鈥� says at the University of Pennsylvania. Prior studies didn鈥檛 do this, he says.

The team found progenitor cells in nine donors. 鈥淚n rodents, it鈥檚 very well known that environmental and genetic factors affect how much neurogenesis there is, so my guess is that differences among humans is due to genetic and environmental factors as well,鈥� says Fris茅n.

The results strongly suggest to Thuret, Song and Salta that adult neurogenesis is real. 鈥淚t really helps the field make a significant step forward, because it鈥檚 adding this missing link,鈥� says Salta.

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鈥淣eurons really are born from cell division that is present during adulthood 鈥� that鈥檚 really what this paper nails down,鈥� says Thuret.

It may one day be possible to study differences in neurogenesis in adults with and without conditions that affect the brain, such as depression and Alzheimer鈥檚, says Thuret. Perhaps drugs that boost this process could lessen symptoms, she wonders.

But at Yale University says that even if new brain cells do form in adults, there may be too few of them to be of therapeutic use. Yet Thuret thinks this is unlikely to be a problem. 鈥淚n mice we see you only need a very small amount to be important for learning [and] memory,鈥� she says.