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Comment by Dr. Krishna Kumari Challa on August 19, 2024 at 11:16am

The two peaks of aging in humans
The progress of a human being through life might be thought of as a mostly gradual succession of changes from the ovum to the grave.
But according to new research into the molecular changes associated with aging, humans experience two drastic lurches forward, one at the average age of 44 and the other at the average age of 60.
We're not just changing gradually over time; there are some really dramatic changes at these peaks. 
It turns out the mid-40s is a time of dramatic change, as is the early 60s. And that's true no matter what class of molecules you look at.
Researchers noticed that in some conditions, such as Alzheimer's and cardiovascular disease, risk doesn't rise gradually with time, it escalates sharply after a certain age.
 Using the samples from their cohort, the researchers have been tracking different kinds of biomolecules. The different molecules studied include RNA, proteins, lipids, and gut, skin, nasal, and oral microbiome taxa, for a total of 135,239 biological features.
Scientists now noticed that there's a very clear change in the abundances of many different kinds of molecules in the human body at two distinct stages.
Around 81 percent of all the molecules they studied showed changes during one or both of these stages. Changes peaked in the mid-40s, and again in the early 60s, with slightly different profiles.

The mid-40s peak showed changes in molecules related to the metabolism of lipids, caffeine, and alcohol, as well as cardiovascular disease, and dysfunctions in skin and muscle. The early 60s peak was associated with carbohydrate and caffeine metabolism, cardiovascular disease, skin and muscle, immune regulation, and kidney function.

The first peak, the mid-40s, is typically when women start undergoing menopause or perimenopause, but the researchers ruled this out as a main factor: men, too, also underwent significant molecular changes at the same age.

This suggests that while menopause or perimenopause may contribute to the changes observed in women in their mid-40s, there are likely other, more significant factors influencing these changes in both men and women

https://www.nature.com/articles/s43587-024-00692-2

Part 1

Comment by Dr. Krishna Kumari Challa on August 19, 2024 at 11:11am

First Major Study Links Cannabis Use Disorder to Deadly Cancers

A new investigation from the American Head and Neck Society finds that excessive cannabis use disorder may increase the risk of developing any head or neck cancer, including oral, oropharyngeal, nasopharyngeal, salivary gland, and laryngeal cancer.

However, the  results should be "interpreted cautiously", as there is a chance they did not fully control for alcohol and tobacco use, as well as HPV status – all of which can contribute to the risk of developing head or neck cancers.

What's more, the study did not measure the amount or the potency of the cannabis participants consumed, how often it was consumed, or how the cannabis was consumed (whether it be vaped, smoked, or ingested).

But this is one of the first studies – and the largest that we know of to date – to associate head and neck cancer with cannabis use. The detection of this risk factor is important because head and neck cancer may be preventable once people know which behaviors increase their risk.

The research relied on 20 years of clinical records belonging to 116,076 individuals diagnosed with a cannabis-related disorder that was "substantial enough to cause physical or emotional symptoms with the inability to cease cannabis use."

This group was then compared to a cohort of nearly 4 million individuals who did not have cannabis use disorder.

In the end, the relative risk of developing head and neck cancer was 3.5 to 5 times greater for those with cannabis use disorder than those without.

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/282...

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Comment by Dr. Krishna Kumari Challa on August 19, 2024 at 11:03am

Spinal cerebrospinal fluid (CSF) leak and  an upright headache

Comment by Dr. Krishna Kumari Challa on August 19, 2024 at 9:44am

Study of fasting and ketogenic diet reveals a new vulnerability of pancreatic tumors

Scientists  have discovered a way to get rid of pancreatic cancer in mice by putting them on a high fat, or ketogenic, diet and giving them cancer therapy.

The cancer therapy blocks fat metabolism, which is the cancer's only source of fuel for as long as the mice remain on the ketogenic diet, and the tumors stop growing.

A scientific team made the discovery, which appears August 14 in Nature, while they were trying to figure out how the body manages to subsist on fat while fasting.

The research team first uncovered how a protein known as eukaryotic translation initiation factor (eIF4E) changes the body's metabolism to switch to fat consumption during fasting. The same switch also occurs, thanks to eIF4E, when an animal is on a ketogenic diet.

They found that a new cancer drug called eFT508, currently in clinical trials, blocks eIF4E and the ketogenic pathway, preventing the body from metabolizing fat. When the scientists combined the drug with a ketogenic diet in an animal model of pancreatic cancer, the cancer cells starved.

The scientists first treated pancreatic cancer with a cancer drug called eFT508 that disables eIF4E, intending to block tumor growth. Yet, the pancreatic tumors continued to grow, sustained by other sources of fuel like glucose and carbohydrates. Knowing that pancreatic cancer can thrive on fat, and that eIF4E is more active during fat burning, the scientists first placed the animals on a ketogenic diet, forcing the tumors to consume fats alone, and then put them on the cancer drug. In this context, the drug cut off the cancer cells' only sustenance—and the tumors shrank.

This method is to treat cancer after knowing its vulnerability and attaining success.

Davide Ruggero, Remodeling of the translatome controls diet and its impact on tumorigenesis, Nature (2024). DOI: 10.1038/s41586-024-07781-7. www.nature.com/articles/s41586-024-07781-7

Comment by Dr. Krishna Kumari Challa on August 18, 2024 at 12:29pm

Bacteria Put on an Invisibility Cloak to Cause Asymptomatic Infections 

Biofilms prevent Pseudomonas aeruginosa toxins from being detected by sensory neurons, tricking the body into not looking sick.

When someone catches a lung infection, be it viral or bacterial, they usually show tell-tale symptoms, such as weakness, breathing difficulties, or brain fog. These indicators signal others to keep a safe distance from the contagious individual. But Pseudomonas aeruginosa can cause a range of lung infections, from mild bronchitis to life-threatening pneumonia, that are acutely asymptomatic yet cause inflammation and destruction of tissue.

In chronic infections, these bacteria form a biofilm of extracellular polymer matrix around themselves that shields them from antimicrobials, enzymes, and neutrophils.² Now, in a paper published in Cell, a group of scientists investigated the underlying mechanism and reported that the biofilm hides Pseudomonas bacteria from sensory neurons in mice, preventing signals from reaching the brain and reducing sickness symptoms. These findings provide a deeper understanding of how biofilm-forming bacteria evade the lung-to-brain communication channel, a potentially crucial tactic in persistent infections. 

https://www.cell.com/cell/abstract/S0092-8674(24)00249-6#%20

Comment by Dr. Krishna Kumari Challa on August 17, 2024 at 11:23am

Cell death types and their relations to host immune pathways

A new review was published as the cover paper of Aging, titled "Types of cell death and their relations to host immunological pathways."

Various immune pathways in the host, such as TH1, TH2, TH3, TH9, TH17, TH22, TH1-like, and THαβ, have been identified. While TH2 and TH9 responses primarily target multicellular parasites, host immune pathways against viruses, intracellular microorganisms (like bacteria, protozoa, and fungi), and extracellular microorganisms utilize programmed cell death mechanisms to initiate immune responses and effectively eliminate pathogens.

These relationships can help us understand the host defense mechanisms against invading pathogens and provide new insights for developing better therapeutic strategies against infections or autoimmune disorders.

Types of Cell Death and Relations to Host Immunological Pathways | Aging-US

Kuo-Cheng Lu et al, Types of cell death and their relations to host immunological pathways, Aging (2024). DOI: 10.18632/aging.206035

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Comment by Dr. Krishna Kumari Challa on August 17, 2024 at 11:06am

Risk for developing type 1 diabetes doubled with paternal link

Individuals are less likely to have type 1 diabetes if their mother has the condition than if their father is affected, according to a study scheduled to be presented at the annual meeting of the European Association for the Study of Diabetes, being held from Sept. 9 to 13 in Madrid.

Researchers conducted a meta-analysis across five cohorts of individuals with type 1 diabetes (total, 11,475 individuals) to compare the proportion of individuals with affected fathers versus mothers.

The researchers found that almost twice as many individuals had an affected father versus mother (overall odds ratio [OR], 1.79). The proportion of individuals with an affected father was higher both among individuals diagnosed with type 1 diabetes older than 18 years (OR, 1.64) and those 18 years or younger (OR, 1.80). There was an excess of individuals with affected fathers only if parental diagnosis was before offspring birth compared with diagnosis after birth. Age at diagnosis and type 1 diabetes-free survival curves were similar among offspring of affected fathers and mothers.

Comment by Dr. Krishna Kumari Challa on August 17, 2024 at 10:58am

A South Asian person with a BMI of around 22 kg/m²—well within the "normal" weight range—has an equivalent risk of type 2 diabetes as a white European person with a BMI of 30 kg/m² (the conventional threshold for obesity).

The adverse metabolic consequences of weight gain in the South Asian men appeared to be related to the size of fat cells at baseline, and the change in the amount of fat in small fat cells.

The South Asians had larger fat cells before weight gain and appeared to be unable to recruit small fat cells to grow into larger fat cells with weight gain. This suggests that, unlike white Europeans, the fat was more likely to go into other areas such as the liver, which can have adverse metabolic consequences.

 found that when young, lean white European men gained a little weight—about 5 kg—they did not experience any substantial adverse metabolic consequences; but when young, lean South Asian men gained the same amount of weight, they started to exhibit metabolic dysfunction.

"Insulin sensitivity decreased by 38% in South Asians, but only by 7% in white Europeans, indicating that South Asians were not able to buffer against the adverse effects of weight gain in the way that their white European counterparts were able to.

This appears to be related, at least in part, to differences in the size of fat cells between South Asian and white European men, and how they respond to the effects of weight gain.

The South Asian men had more large fat cells, and the very small fat cells that they had were less able to grow in size as they put on weight. Both these factors were related to the adverse metabolic changes with weight gain.

Another interesting observation was that when the European men put on weight, they put on some lean tissue as well as fat tissue, but the South Asian men essentially just put on fat tissue.

This may be important, as increasing lean tissue may help protect against some of the adverse effects of weight gain, as sugar is cleared from the blood in lean tissue, or muscle.

The study's findings reinforce the need for the prevention of weight gain in South Asian men, in order to prevent further risk of type 2 diabetes.

James McLaren et al, Weight gain leads to greater adverse metabolic responses in South Asian compared with white European men: the GlasVEGAS study, Nature Metabolism (2024). DOI: 10.1038/s42255-024-01101-z

Part 2

Comment by Dr. Krishna Kumari Challa on August 17, 2024 at 10:55am

Weight gain appears to have greater metabolic consequences in South Asian men

Gaining even a small amount of weight may lead to adverse metabolic responses in young South Asian men according to new research.

The study— published in Nature Metabolism—may shed light on why South Asians are at greater risk of developing type 2 diabetes compared with other ethnic groups, and why their risk of diabetes increases more steeply with increasing BMI.

The research—which is part of the GlasVegas (Glasgow visceral and ectopic fat with weight gain in South Asians) study—investigated 14 young normal weight men of South Asian ethnic origin and 21 men of white European ethnicity before and after an overfeeding protocol to gain approximately 5 kg in weight ( please note the small sample size).

The main finding was that this modest weight gain resulted in substantial adverse metabolic responses in the South Asian men. In contrast, the white European men appeared to exhibit a degree of "metabolic buffering capacity," such that the same weight gain led to much smaller metabolic changes. Insulin sensitivity—or how well body tissues respond to insulin—decreased by 38% in the South Asian men, but only by 7% in the white Europeans.

South Asians comprise about a quarter of the world's population and have 3–5 times the prevalence of type 2 diabetes compared to white Europeans. South Asians also develop type 2 diabetes at much lower BMIs (Body Mass Indexes) than white Europeans.

Part 1

Comment by Dr. Krishna Kumari Challa on August 17, 2024 at 10:45am

Uterus transplants are leading to healthy pregnancies

till now, that is.

Uterine transplants are relatively rare and recent—the first was performed in 2011, and to date a little more than 100 transplants have been conducted worldwide.

However, a new study finds that these procedures are often successful, leading to pregnancies and live births in 14 out of the 20 patients assessed.

"A successfully transplanted uterus is capable of functioning at least on par with a native, in situ uterus," concluded a research team who assessed the outcomes.

As the researchers explained, uterus transplants are typically needed by women with what's known as "absolute uterine infertility," a condition affecting about 1 in every 500 women where the organ is either dysfunctional or absent.

In the past, these women would have had to resort to adoption or surrogacy, but 13 years ago doctors first transplanted a donated uterus into a woman with uterine infertility.

Since then, the procedure has gained acceptance.

Just how successful are these transplants?

The Dallas team tracked outcomes for 20 women averaging 30 years of age who opted for uterus transplant at their facility between 2016 and 2019.

Organs came from 18 living donors and 2 deceased donors.

In 14 of the women who underwent uterus transplant, the operation was successful, the study found, and "all 14 recipients gave birth to at least 1 live-born infant."

Complications were common and occurred in 50% of these pregnancies, with gestational high blood pressure and preterm labor being two of the most common. However, "congenital abnormalities and developmental delays have not occurred to date in [any of] the live-born children," the researchers noted. Overall, uterus transplant was "technically feasible and was associated with a high live birth rate," the team concluded.

Giuliano Testa et al, Uterus Transplant in Women With Absolute Uterine-Factor Infertility, JAMA (2024). DOI: 10.1001/jama.2024.11679

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