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Cells Across the Body Talk to Each Other About Aging

News Agency nabakhabar — Tue, 16 Jan 2024 18:04:23 +0000

Aging can seem like an unregulated process: As time marches along, our cells and bodies inevitably accumulate dings and dents that cause dysfunctions, failures and ultimately death. However, in 1993 a discovery upended that interpretation of events.

Researchers found a mutation in a single gene that doubled a worm’s life span; subsequent work showed that related genes, all involved in the response to insulin, are key regulators of aging in a host of animals, from worms and flies to humans. The discovery suggested that aging is not a random process — indeed, specific genes regulate it — and opened the door to further research into how aging proceeds at a molecular level.

Recently, a set of papers documented a new biochemical pathway that regulates aging, one based on signals passed between mitochondria, the organelles best known as the powerhouse of the cell. Working with worms, the researchers found that damage to mitochondria in brain cells triggered a repair response that was then amplified, setting off similar reactions in mitochondria throughout the worm’s body. The effect of this repair activity was to extend the organism’s life span: The worms with repaired mitochondrial damage lived 50% longer.

What’s more, cells in the germline — the cells that produce eggs and sperm — were central to this anti-aging communication system. It’s a finding that adds new dimensions to the fertility concerns implied when people talk about aging and their “biological clock.” Some of the findings were reported in Science Advances and others were posted on the scientific preprint server biorxiv.org in the fall.

The research builds on a recent body of work that suggests that mitochondria are social organelles that can talk to one another even when they are in different tissues. In essence, the mitochondria function as cellular walkie-talkies, sending messages throughout the body that influence the survival and life span of the entire organism.

“The important thing here is that in addition to genetic programs, there is also a very important factor to regulate aging, which is the communication between tissues,” said David Vilchez, who studies aging at the University of Cologne and was not involved in the new research.

The cell biologist Andrew Dillin discovered the first hints of this novel pathway that regulates life span about a decade ago. He was hunting for life-extending genes in Caenorhabditis elegans worms when he found that genetically damaging the mitochondria extended the worms’ lives by 50%.

That was unexpected. Dillin had assumed that defective mitochondria would hasten death rather than prolong life — after all, mitochondria are central to cell functioning. Yet for some reason, gumming up the smooth functioning of the mitochondria compelled the worms to live longer.

More intriguing was the fact that damaged mitochondria in the worms’ nervous system seemed to be driving the effect. “It really says that some mitochondria are more important than others,” said Dillin, who is now a professor at the University of California, Berkeley. “The neurons dictate this over the rest of the organism, and that was really surprising.”

Now, Dillin and his team have expanded that finding by discovering new details about how mitochondria in the brain communicate with cells across the worm’s body to extend life.

First, he had to understand why damage to the brain’s mitochondria could possibly have a beneficial effect on the organism. A mitochondrion’s process for generating energy requires exceedingly complex molecular machinery with dozens of different protein parts. When things go awry, such as when some components are missing or misfolded, mitochondria activate a stress response, known as the unfolded protein response, which delivers repair enzymes to help the complexes assemble properly and restore mitochondrial function. In this way, the unfolded protein response keeps cells healthy.

Dillin expected this process to unfold only inside the neurons with damaged mitochondria. Yet he observed that cells in other tissues of the worm’s body also turned on repair responses even though their mitochondria were intact.

It’s this repair activity that helped the worms live longer. Like taking a car to a mechanic regularly, the unfolded protein response seemed to keep cells in good running order and function as anti-aging detailing. What remained mysterious was how this unfolded protein response was communicated to the rest of the organism.

After some investigation, Dillin’s team discovered that the mitochondria in stressed neurons were using vesicles — bubblelike containers that move materials around the cell or between cells — to carry a signal called Wnt beyond the nerve cells to other cells in the body. Biologists already knew that Wnt plays a role in setting up the body pattern during early embryonic development, during which it also triggers repair processes like the unfolded protein response. Still, how could Wnt signaling, when turned on in an adult, avoid activating the embryonic program?

Dillin suspected that there had to be another signal that Wnt interacted with. After further work, the researchers discovered that a gene expressed in the mitochondria of the germline — and in no other mitochondria — can interrupt Wnt’s developmental processes. That result suggested to him that germline cells play critical roles in relaying the Wnt signal between the nervous system and tissues throughout the rest of the body.

“The germline is absolutely essential for this,” Dillin said. It isn’t clear, however, whether the germline mitochondria act as amplifiers, receiving the signal from the brain’s mitochondria and transmitting it to other tissues, or if the receiving tissues are “listening” for signals from both sources.

Either way, the strength of the germline signal regulates the organism’s life span, Dillin said. As a worm ages, the quality of its eggs or sperm declines — what we refer to as the ticking of a biological clock. The decline is also reflected in the germ cells’ changing ability to transmit signals from the brain’s mitochondria, he suggested. As the worm grows older, its germline transmits the repair signal less effectively, and so its body declines, too.

Scientists don’t yet know whether these findings apply to humans and how we age. Still, the hypothesis makes sense from a broader evolutionary standpoint, Dillin said. As long as the germ cells are healthy, they send pro-survival signals to ensure that their host organism survives to reproduce. But as the quality of the germ cells declines, there is no evolutionary reason to keep extending life span further; from evolution’s perspective, life exists to reproduce itself.

The fact that mitochondria can talk among themselves might seem somewhat alarming, but there is an explanation. Long ago, mitochondria were free-living bacteria that joined forces with another type of primitive cell to work together in what became our modern complex cells. So, their ability to communicate is probably a relic from the free-living bacterial ancestor of mitochondria.

“This little thing that’s been ticking inside of cells for billions of years still retains its bacterial origins,” Dillin said. And if his research in worms holds up in more complex organisms like humans, it’s possible that your mitochondria are talking right now about your age.

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Are Different Races Incompatible? Far From It.

News Agency nabakhabar — Sat, 04 Nov 2023 10:31:17 +0000

Our family has two cats, and I’ve often found myself wondering what it’s like to be them. I imagined them driven by a host of competing innate instincts—desire for food, affection, sleep, etc.—and ultimately following the ones that are the strongest at the moment. Humans, on the other hand, can intentionally regulate and suppress instincts that we find unproductive or harmful. But in the end, I’ve concluded that humans and cats are so deeply different that I can’t accurately imagine their experience, so I’ve given up trying.

Are white and Black people like this? That is, are they so different that they should give up trying to understand each other? If this question sounds absurd to you, we’re on the same page. Still, this is a question worth asking because unfortunately, it is a relatively common sentiment that Black and white people are so fundamentally different that it’s futile for the two to even try to genuinely relate to each other. And it feels a lot like racial groups are being treated like different species—as if there’s little shared ground that can be identified. The negative implications of adopting such an outlook are severe for the relationships that hold society together. But the good news is that we can do something about it if we take this seriously enough.

Are Interracial Connections Futile?

The most recent example of the bleak racial relational outlook I’ve seen involved an interview with Kehinde Andrews about his new book, “The Psychosis of Whiteness.” In fairness, Andrews says his intent is not to generalize psychosis to all white people and that whiteness has less to do with skin color than an acceptance of a Eurocentric worldview. But it’s worth noting that psychosis is a condition characterized by a break from reality, and at its worst, it literally renders people suffering from it unrelatable. So to the extent that people hold this view, he argues, they’re impossible to reason and connect with. And it stands to reason that most of these people would be white.

This view of the futility of meaningful interracial relationships is becoming more mainstream and is well-represented in several top-selling books on race. For example, in his bestselling “Between the World and Me,” Ta-Nehisi Coates said he “will teach [his] boys to have profound doubts that friendship with white people is possible.” In her bestselling “White Fragility,” Robin DiAngelo famously recommended that white women should not cry in front of Black people because it triggers traumatic historical memories of distressed white women as the cause for many Black men’s torture and murder. I contend that if you feel forbidden to cry in front of someone, you do not and cannot have a close relationship with that person.

I’m also reminded of one psychiatrist’s talk at the Yale Child Study Center a couple of years back. Her lecture, entitled “The Psychopathic Problem of the White Mind,” consisted of a litany of opinions about the deep dysfunction of white people (not whiteness as a concept). Her expressed fantasy of shooting white people captured headlines. But as disturbing as this was, what concerned me even more was something she did. Claiming that when it came to white people, there were “no good apples,” she said she had “ghosted” her white friends a few years earlier.

Now, I’m Black, and most of my closest friends are also Black, but I couldn’t imagine thinking about or treating my white friends in that way because to me friendship means a connection that is deep, durable and very personal, not group- or identity-based. The thought that “I need to purge my white/Black friends” is inconceivable, especially when the characteristic under consideration is an immutable physical characteristic, not something any of us choose.

A Race-Based ‘Relational Pessimism’

What all these examples reflect is what I think of as a race-specific case of relational pessimism. This is the idea that forming genuine, mutually caring relationships across the color line is hopeless, either because white and Black experiences are too different from each other or because white people are too attached to the advantages of their whiteness to care enough for Black people. Admittedly, sometimes relational pessimism is warranted: For example, a relationship between a Christian fundamentalist and a staunch atheist is not likely to work out. The same is true for a relationship between an ardent follower of Black Lives Matter and a vehement supporter of Donald Trump. But these represent extremes, not the norm, and one’s race is certainly not a viewpoint.

The central claim of this type of relational pessimism is obviously false. To be true, it would mean that the countless interracial friendships and romantic relationships are dysfunctional or fake, despite the fact that such relationships have experienced rapid growth in the U.S. over the last 50 years. But more importantly, it pollutes and cheapens interpersonal dynamics by reducing individuals in “other” groups to group representatives you can only relate to by way of cultural brokers or allyship—never as true colleagues, friends, or life partners.

In the worst of cases, race-based relational pessimism encourages some white people to acquire and flaunt vanity interracial “friendships,” where the goal is to convince themselves and their social groups of their good progressive values. Under these circumstances, interracial relationships become a means for self-congratulation or boosting social status—tokenism on steroids. When some white people on the right take race-based relational pessimism seriously, it can result in what we’ve seen from the likes of Scott Adams, the “Dilbert” comic strip creator, who implored other white people “to get the hell away from Black people” after learning that 47% of Black people indicated that they either disagreed or were unsure in response to the statement “It’s OK to be white.”

For Black people, race-based relational pessimism encourages attributing all unpleasant interracial interactions to white people’s whiteness, like the “Victoria’s Secret Karen” incident, where a white woman aggressively asked a Black woman to give her space in line at Victoria’s Secret during the pandemic. When the offended Black woman started recording her, the white woman had an emotional outburst—a “Karen” moment—that seems more realistically explained by her developmental disability than her race.

Additionally, this kind of race-based relational pessimism can pervert group cohesiveness in ways that lead to supporting others with superficial similarities even when they commit acts of inhumanity. This happened when Chicago’s Black Lives Matter chapter celebrated, and then backtracked from, Hamas’ slaughter of innocent people.

Societal Consequences

Commitment to race-based relational pessimism also has big societal implications. A functional democracy depends on its people having some trust in their ability to find common ground. But this can’t happen if we believe that entire groups of individuals can’t relate to each other at all. This is a disaster in the making, as a natural consequence of this is for people to harden their in-group boundaries and position themselves against out-groups. It perfectly sets the stage for intense culture wars and potentially real wars, consisting of allies and enemies—and that’s essentially where we find ourselves today.

Before we can start cleaning up this mess, we must first become clear on one of the big drivers of the problem. It’s common for movements attempting to correct an injustice to go too far, and this is what’s happening now. In a reasonable and well-intentioned effort to correct racism and appreciate diversity, we’ve gone to the extreme of overemphasizing difference and identity to the point that we’ve lost sight of our deeper common humanity. Yascha Mounk does an excellent job of tracing the ideological roots of this overcorrection in his new book, “The Identity Trap.”

I point to these liberal failures precisely because I am a liberal. Certainly, the far right has contributed in its own ways to the race-based relational pessimism we see in America. For example, some on the right would rather resort to censorship than do the hard work of changing hearts and minds. But as a liberal myself, I’m especially concerned about liberals abandoning liberalism—in particular, abandoning values of tolerance and individualism. Furthermore, there is no shortage of critiques from liberals against the far right, but there is a shortage of liberal self-reflection.

What to Do?

Although there are good reasons for us to be pessimistic about relationships between races, it’s not the end of the road yet. There are some things we can all do to improve the situation, and schools and parents play crucial roles.

Teach dialogue and debate. It certainly seems that our ability to engage people with different viewpoints has atrophied over the past decade or so. Anecdotal evidence is everywhere, from polarized politics to increased racial and gender tensions to social media mobbing, doxxing and other forms of cyberbullying. If the adults are too far gone, the least we can do is endow our youth with the necessary skills to engage others with different views and to learn something in the process. This can happen through actively incorporating skill development in dialogue and debate in schools. Organizations like The Mill Institute and Braver Angels are doing fantastic work in this area, and aspects of social and emotional learning programs are also relevant for developing these abilities.

Improve civics and history education. With interpersonal alienation and political polarization increasing at such a fast clip, I’ve often wondered about the possibility of another U.S. civil war. But a recent conversation with Paul Carrese, director of the School of Civic and Economic Thought and Leadership at Arizona State University, convinced me that a much more likely scenario is societal disintegration. That is, we become so cynical, disillusioned and, yes, pessimistic about the American project and our fellow citizens that we just give up trying to forge a society together and it collapses as a result.

This may not sound as tragic as a civil war. But in such a state, who is going to care enough to help the vulnerable, to improve and sustain our many institutions, and to protect us from foreign and domestic enemies? Why give so much of yourself to these projects when you feel that the out-groups are alien to you or unworthy of your effort?

Strengthening our civics and history education would not only help create a more civics- and history-literate citizenry, but it would also help diminish relational pessimism by emphasizing our shared responsibilities to each other. It also reminds us of the many times we and other societies have successfully bridged bigger divides than the ones we’re experiencing now. And of course, it’s essential that the teaching of civics and history be honest and reflective of all the diverse people and perspectives of our country. “Educating for American Democracy,” a report developed by politically diverse scholars, educators and practitioners, including Harvard’s Danielle Allen, has done a great job of this and provides a solid roadmap for what our schools can do to get us there.

Shape values and principles. When figuring out how to relate to others and their ideas, it helps to have a core set of principles and values. Otherwise, you’re more susceptible to following the next popular set of social rules that emerge, especially in the powerfully influential world of social media. Parents can play a central role in this process by shaping and guiding these value systems. For example, we use two strategies in our household to support this. To promote open-mindedness and critical thinking when relating to others, we encourage our son to respectfully ask, “How do you know?” when a claim is made to him that doesn’t make sense. This conveys that just because something doesn’t make sense, it doesn’t mean it’s wrong. So request the reasoning and hear it out. But if the person can’t offer it, you shouldn’t blindly accept that idea.

And to remind our son to be compassionate and tolerant to others, we encourage him to remember that “everyone is working on something.” This includes him, Mom and Dad, and we’re open with him about where we’re trying to grow. To maximize kids’ ability to relate to the widest range of people, the instilled values should not be overly specific to one’s identity group. That is, they need to include universal values—values like respect for diversity and curiosity about others’ views and cultures. This doesn’t require discarding culture-specific values: It just means that when it comes to navigating a diverse social world, culture-specific values aren’t sufficient by themselves unless they’re connected to broader ones.

Foster relational optimism. I want a world where people evaluate the substance of ideas, individuals and relationships, not the physical or ideological markers of them. It’s possible but requires a kind of relational optimism—a belief that it’s not only possible but desirable to form real relationships with others who are different in appearance, thought and behavior. It also requires a very different kind of “doing the work” from interrogating and acknowledging one’s group-level privilege and power and calling out microaggressions.

It means developing an ability to see an individual in front of you, rather than an abstract racial representation. Seeing a person as an individual first and foremost will enable you to engage with them as such rather than using a set of artificial predetermined rules of engagement defined by race gurus. One key civic virtue recommended by the “Educating for American Democracy” report I mentioned above is “civic friendship”—the idea that we are “in this together” and that we can respect our philosophical and partisan differences because we have a deeper respect for each other as fellow Americans. But for this to work, we need enough people committed to the idea.

At the end of the day, the health of our society depends on the strength of our social compacts. So it’s the social fabric of our society that’s at stake for us as we actively drive away from each other. We should treat this with the seriousness it deserves by committing to be weavers of a more connected social fabric.

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WHO report: COVID likely 1st jumped into humans from animals

News Agency nabakhabar — Mon, 29 Mar 2021 20:37:21 +0000

A joint World Health Organization-China study on the origins of COVID-19 says that transmission of the virus from bats to humans through another animal is the most likely scenario and that a lab leak is “extremely unlikely,” according to a draft copy obtained by The Associated Press.

The findings offer little new insight into how the virus first emerged and leave many questions unanswered. But the report does provide more detail on the reasoning behind the researchers’ conclusions.

The team proposed further research in every area except the lab leak hypothesis — a speculative theory that was promoted by former U.S. President Donald Trump among others. It also said the role played by a seafood market where human cases were first identified was uncertain.

Dr. Anthony Fauci, the top U.S. infectious diseases expert, said he would like to see the report’s raw information first before deciding about its credibility.

“I’d also would like to inquire as to the extent in which the people who were on that group had access directly to the data that they would need to make a determination,” he said. “I want to read the report first and then get a feel for what they really had access to — or did not have access to.”

The report, which is expected to be made public Tuesday, is being closely watched since discovering the origins of the virus could help scientists prevent future pandemics — but it’s also extremely sensitive since China bristles at any suggestion that it is to blame for the current one.

Matthew Kavanagh of Georgetown University said the report deepened the understanding of the virus’s origins, but more information was needed.

“It is clear that that the Chinese government has not provided all the data needed and, until they do, firmer conclusions will be difficult,” he said in a statement.

Last year, an AP investigation found the Chinese government was strictly controlling all research into its origins. And repeated delays in the report’s release have raised questions about whether the Chinese side was trying to skew its conclusions.

“We’ve got real concerns about the methodology and the process that went into that report, including the fact that the government in Beijing apparently helped to write it,” U.S. Secretary of State Antony Blinken said in a recent CNN interview.

China rejected that criticism Monday.

“The U.S. has been speaking out on the report. By doing this, isn’t the U.S. trying to exert political pressure on the members of the WHO expert group?” asked Foreign Ministry spokesperson Zhao Lijian.

Still, suspicion of China has helped fuel the theory that the virus escaped from a lab in Wuhan, the Chinese city where the virus was first identified. The report cited several reasons for all but dismissing that possibility.

Full Coverage: Coronavirus pandemic

It said that such laboratory accidents are rare, that the labs in Wuhan were well-managed and there is no record of viruses closely related to the coronavirus in any laboratory before December 2019.

The report is based largely on a visit by a WHO team of international experts to Wuhan. The mission was never meant to identify the exact natural source of the virus, an endeavor that typically takes years. For instance, more than 40 years of study has still failed to pinpoint the exact species of bat that are the natural reservoir of Ebola.

In the draft obtained by the AP, the researchers listed four scenarios in order of likelihood for the emergence of the new coronavirus. Topping the list was transmission from bats through another animal, which they said was likely to very likely. They evaluated direct spread from bats to humans as likely, and said that spread to humans from the packaging of “cold-chain” food products was possible but not likely.

That last possibility was previously dismissed by the WHO and the U.S. Centers for Disease Control and Prevention but researchers on this mission have taken it up again, further raising questions about the politicization of the study since China has long pushed the theory.

While it’s possible an infected animal contaminated packaging that was then brought to Wuhan and infected humans, the report said the probability is very low.

Mark Woolhouse, an epidemiologist at the University of Edinburgh, said even that “very low probability” was an overstatement. “There’s no compelling evidence of people actually being infected through packaging,” he said, calling the theory “far-fetched.”

Woolhouse said it was possible the source of COVID-19 might never be identified.

“The emergence of a new (disease) is always a sequence of unlikely events,” he said. “It’s hard to be definitive and rule anything out.” But he said most scientists agree that bats are the most likely source.

Bats are known to carry coronaviruses and, in fact, the closest relative of the virus that causes COVID-19 has been found in bats.

The report said highly similar viruses have been found in pangolins, a scaly anteater prized in traditional Chinese medicine, but scientists have yet to identify the same coronavirus in animals that has been infecting humans.

The AP received the draft copy on Monday from a Geneva-based diplomat from a WHO-member country. It wasn’t clear whether the report might still be changed prior to release, though the diplomat said it was the final version. A second diplomat confirmed getting the report too. Both refused to be identified because they were not authorized to release it ahead of publication.

WHO Director-General Tedros Adhanom Ghebreyesus acknowledged he had received the report over the weekend and said it would be formally presented Tuesday.

“All hypotheses are on the table and warrant complete and further studies,” he said at a news conference.

The report is inconclusive on whether the outbreak started at a Wuhan seafood market that had one of the earliest clusters of human cases in December 2019. Research published last year in the journal Lancet suggested the market may have merely served to further spread the disease rather than being its source.

The market was an early suspect because some stalls sold a range of unusual animals — and some wondered if they had brought the new virus to Wuhan. The report noted that animal products — including everything from bamboo rats to deer, often frozen — were sold at the market, as were live crocodiles.

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Ken Moritsugu reported from Beijing. Associated Press writers Maria Cheng in London, Victoria Milko in Jakarta, Indonesia, Zeke Miller in Washington, and Frank Jordans in Berlin, contributed to this report.

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The AP Health and Science Department receives support from the Howard Hughes Medical Institute’s Department of Science Education. The AP is solely responsible for all content.

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