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The Sinclair group's NAD paper drew attention partly because it showed a novel way that NAD and sirtuins work together. The researchers discovered that cells' nuclei send signals to mitochondria that are needed to maintain their normal operation. SIRT1 helps insure the signals get through. When NAD levels drop, as they do with aging, SIRT1 activity falls off, which in turn makes the crucial signals fade, leading to mitochondrial dysfunction and all the ill effects that go with it.

Test-tube and rodent studies also suggest that pterostilbene is more potent than resveratrol when it comes to improving brain function, warding off various kinds of cancer and preventing heart disease.

researchers were also able to activate the mitochondrial UPR via pharmacological means. Dosing worms with the antibiotic doxycyline, which inhibits bacterial and mitochondrial protein translation, also activated the mitochondrial UPR and extended worm lifespans. Rapamycin, shown to enhance longevity in mice, also extended worm lifespan and induced mitonuclear protein imbalance and the mitochondrial UPR in mouse hepatocytes.

mitochondrial ribosomal proteins are not to be trifled with. “There are a number of well-defined severe disorders in humans, including neonatal lethality, due to defects in those exact proteins,”

is beginning to cast a wider net, looking to see whether mitonuclear protein imbalance could explain longevity induced by other means, such as caloric restriction. Auwerx hopes that the work will aid in designing a drug intervention “to pump up this response via pharmacological tools.”

he’s optimistic that his team has identified a “common thread” demonstrating that longevity is not affected so much by inhibiting or stimulating mitochondria, but how the organelles “deal with proteins.”

Maybe not, according to an admonitory new study of the molecular effects of high-intensity interval training

suggesting that the benefits of extremely vigorous exercise may depend on just how much we do.

for example, that intense bursts of exercise increase the number of mitochondria in our muscle cells, and more mitochondria are thought to contribute to better cellular and metabolic health.

HIIT also may have unexpected downsides. In a study I wrote about in January, people who worked out with HIIT routines three times a week for six weeks did not improve their blood pressure or body fat as much as people who exercised far more moderately five times a week.

by being sedentary for four days each week, the intense exercisers in the study may have undermined the otherwise potent effects of their HIIT sessions.

These volunteers visited the researchers’ lab for tests of their current fitness and metabolic health, including blood-sugar levels over the course of a day.

Then they compared how people’s bodies had changed week over week.

At first, the findings were encouraging. By the end of week two, the riders were pedaling harder and appeared to be getting fitter, with better daily blood-sugar control and more total mitochondria in their muscle cells.

But something began to go wrong during week three. The volunteers’ ability to generate power while cycling flattened, and their subsequent muscle biopsies showed sputtering mitochondria, each of which was now producing only about 60 percent as much energy as during the previous week. The riders’ blood-sugar control also slipped, with se

The researchers are not sure precisely what changes within their volunteers’ bodies and muscles precipitated the negative results in week three.

Even so, the findings strongly suggest that anyone interested in high-intensity interval training start small, Mr. Flockhart says. Train a few times a week and on the remaining days, maybe take a walk.

In support of that idea, half a dozen Nobel laureates and other prominent scientists are working with two small companies offering NR supplements.

This time his lab made headlines by reporting that the mitochondria in muscles of elderly mice were restored to a youthful state after just a week of injections with NMN (nicotinamide mononucleotide), a molecule that naturally occurs in cells and, like NR, boosts levels of NAD.

NAD boosters might work synergistically with supplements like resveratrol to help reinvigorate mitochondria and ward off diseases of aging

a single dose of NR resulted in statistically significant increases” in NAD in humans—the first evidence that supplements could really boost NAD levels in people.

When NAD levels drop, as they do with aging, SIRT1 activity falls off, which in turn makes the crucial signals fade, leading to mitochondrial dysfunction and all the ill effects that go with it.

It should be noted, however, that muscle strength was not improved in the NMN-treated mice

Test-tube and rodent studies also suggest that pterostilbene is more potent than resveratrol when it comes to improving brain function, warding off various kinds of cancer and preventing heart disease.

Even before Sinclair's paper, researchers had shown in 2012 that when given doses of NR, mice on high-fat diets gained 60 percent less weight than they did on the same diets without NR. Further, none of the mice on NR showed signs of diabetes, and their energy levels improved. The scientists reportedly characterized NR's effects on metabolism as "nothing short of astonishing."

In the late 1900s, researchers discovered that mitochondria were free-living bacteria at some point in the past. Somehow they were drawn inside another cell, providing new fuel for their host. In 2015, Thijs Ettema of Uppsala University in Sweden and his colleagues discovered fragments of DNA in sediments retrieved from the Arctic Ocean. The fragments contained genes from a species of archaea that seemed to be closely related to eukaryotes.Dr. Ettema and his colleagues named them Asgard archaea. (Asgard is the home of the Norse gods.) DNA from these mystery microbes turned up in a river in North Carolina, hot springs in New Zealand and other places around the world.

Masaru K. Nobu, a microbiologist at the National Institute of Advanced Industrial Science and Technology in Tsukuba, Japan, and his colleagues managed to grow these organisms in a lab. The effort took more than a decade.The microbes, which are adapted to life in the cold seafloor, have a slow-motion existence. Prometheoarchaeum can take as long as 25 days to divide. By contrast, E. coli divides once every 20 minutes.

In the lab, the researchers mimicked the conditions in the seafloor by putting the sediment in a chamber without any oxygen. They pumped in methane and extracted deadly waste gases that might kill the resident microbes.The mud contained many kinds of microbes. But by 2015, the researchers had isolated an intriguing new species of archaea. And when Dr. Ettema and colleagues announced the discovery of Asgard archaea DNA, the Japanese researchers were shocked. Their new, living microbe belonged to that group.The researchers then undertook more painstaking research to understand the new species and link it to the evolution of eukaryotes.The researchers named the microbe Prometheoarchaeum syntrophicum, in honor of Prometheus, the Greek god who gave humans fire — after fashioning them from clay.

This finding suggests that the proteins that eukaryotes used to build complex cells started out doing other things, and only later were assigned new jobs.Dr. Nobu and his colleagues are now trying to figure out what those original jobs were. It’s possible, he said, that Prometheoarchaeum creates its tentacles with genes later used by eukaryotes to build cellular skeletons.

Before the discovery of Prometheoarchaeum, some researchers suspected that the ancestors of eukaryotes lived as predators, swallowing up smaller microbes. They might have engulfed the first mitochondria this way.

Instead of hunting prey, Prometheoarchaeum seems to make its living by slurping up fragments of proteins floating by. Its partners feed on its waste. They, in turn, provide Prometheoarchaeum with vitamins and other essential compounds.

The technique holds the power to repair or enhance any human gene. “It raises the most fundamental of issues about how we are going to view our humanity in the future and whether we are going to take the dramatic step of modifying our own germline and in a sense take control of our genetic destiny, which raises enormous peril for humanity,”

The paper’s authors, however, are concerned about countries that have less regulation in science. They urge that “scientists should avoid even attempting, in lax jurisdictions, germline genome modification for clinical application in humans” until the full implications “are discussed among scientific and governmental organizations.”

Though such a moratorium would not be legally enforceable and might seem unlikely to exert global influence, there is a precedent. In 1975, scientists worldwide were asked to refrain from using a method for manipulating genes, the recombinant DNA technique, until rules had been established.

Though highly efficient, the technique occasionally cuts the genome at unintended sites. The issue of how much mistargeting could be tolerated in a clinical setting is one that Dr. Doudna’s group wants to see thoroughly explored before any human genome is edited.

“We worry about people making changes without the knowledge of what those changes mean in terms of the overall genome,” Dr. Baltimore said. “I personally think we are just not smart enough — and won’t be for a very long time — to feel comfortable about the consequences of changing heredity, even in a single individual.”

Many ethicists have accepted the idea of gene therapy, changes that die with the patient, but draw a clear line at altering the germline, since these will extend to future generations. The British Parliament in February approved the transfer of mitochondria, small DNA-containing organelles, to human eggs whose own mitochondria are defective. But that technique is less far-reaching because no genes are edited.

There are two broad schools of thought on modifying the human germline, said R. Alta Charo, a bioethicist at the University of Wisconsin and a member of the Doudna group. One is pragmatic and seeks to balance benefit and risk. The other “sets up inherent limits on how much humankind should alter nature,” she said. Some Christian doctrines oppose the idea of playing God, whereas in Judaism and Islam there is the notion “that humankind is supposed to improve the world.” She described herself as more of a pragmatist, saying, “I would try to regulate such things rather than shut a new technology down at its beginning.

The Doudna group calls for public discussion, but is also working to develop some more formal process, such as an international meeting convened by the National Academy of Sciences, to establish guidelines for human use of the genome-editing technique.“We need some principled agreement that we want to enhance humans in this way or we don’t,” Dr. Jaenisch said. “You have to have this discussion because people are gearing up to do this.”

“coupled with the concerns about drug-resistance. . . one should only use antibiotics when you really need antibiotics.”