By surgically joining together the circulatory systems of a young and old mouse, scientists were able to slow the aging process at the cellular level and lengthens the lifespan of the older animal by up to 10%. Published in Nature Aging, the Duke Health-led team also found that that the longer the animals shared circulation, the longer the anti-aging benefits lasted once the two were separated.
The findings suggest a cocktail of components and chemicals in the blood of the young contributes to vitality, and these factors could potentially be isolated as therapies to speed healing, rejuvenate the body and add years to an older individual’s life. (Joining up the circulatory systems of young and old humans should hopefully remain the stuff of dystopian science fiction novels).
“This is the first evidence that the process, called heterochronic parabiosis, can slow the pace of aging, which is coupled with the extension in lifespan and health,” said senior author James White, PhD, assistant professor at Duke University School of Medicine.
White and colleagues set out to determine whether the benefits of heterochronic parabiosis, surgically fusing two animals of different ages to enable a shared circulatory system, were fleeting, or more long-lasting.
Earlier studies at Duke and elsewhere documented anti-aging benefits in tissues and cells of the older mice after three weeks of parabiosis. These studies found that the older mice became more active and animated, and their tissue showed evidence of rejuvenation.
“Our thought was, if we see these anti-aging effects in three weeks of parabiosis, what happens if you bring that out to 12 weeks,” White said. “That’s about 10% of a mouse’s lifespan of three years.”
White said the ages of the mice were also important, with the young mouse aged four months, and the older mouse aged two years.
With follow-up during a two-month detachment period, the older animals exhibited improved physiological abilities and lived 10% longer than animals that had not undergone the procedure.
At the cellular level, parabiosis drastically reduced the epigenetic age of blood and liver tissue, and showed gene expression changes opposite to aging, but akin to several lifespan-extending interventions such as calorie restriction.
The rejuvenation effect persisted even after two months of detachment.
In human terms, the parabiosis exposure would be the equivalent of pairing a 50 year-old with an 18-year-old for about eight years, with the effects adding eight years to the person’s lifespan.
White said the experiment was designed to study if long-term exposure of young blood will cause lasting effects in the old mouse. Pairing humans for heterochronic parabiosis is obviously not practical or even ethical, he said. He also noted that other anti-aging strategies, such as calorie restriction, work better to extend longevity in mice.
“Our work points to a need to explore what factors in the circulation of youthful blood cause this anti-aging phenomenon” White said. “We have demonstrated that this shared circulation extends life and health for the older mouse, and the longer the exposure, the more permanent the changes.
“The elements that are driving this are what’s important, and they are not yet known,” White said. “Are they proteins or metabolites? Is it new cells that the young mouse is providing, or does the young mouse simply buffer the old, pro-aging blood? This is what we hope to learn next.”
Conventional wisdom holds that abdominal fat accumulation increases the risk for type 2 diabetes. But surprising new findings from the University of Virginia School of Medicine suggest that naturally occurring genetic variations in our genes can lead some people to store fat at the waist but also protect them from diabetes.
The unexpected discovery, which is published in eLife, provides a more nuanced view of the role of obesity in diabetes and related health conditions. It also could pave the way for more personalised medicine, such as prioritising weight loss for patients whose genes put them at increased risk but place less emphasis on it for patients with protective gene variants, the researchers say.
“There is a growing body of evidence for metabolically healthy obesity. In this condition, people who would normally be at risk for cardiovascular diseases and diabetes because they are obese are actually protected from adverse effects of their obesity. In our study, we found a genetic link that may explain how this occurs in certain individuals,” said researcher Mete Civelek, PhD, of UVA’s Center for Public Health Genomics. “Understanding various forms of obesity is important to tailor treatments for individuals who are at high risk for adverse effects of obesity.”
As medicine grows more sophisticated, understanding the role of naturally occurring gene variations will play an important role in ensuring patients get the best, most tailored treatments. The new work by Civelek and his team, for example, indicates that variants can simultaneously predispose some people to store fat at the abdomen, thought to put them at increased risk for metabolic syndrome, while also protecting them from type 2 diabetes. (Metabolic syndrome raises the risk for diabetes, stroke and other serious health issues.)
One of the metrics doctors use to determine if a patient has metabolic syndrome is abdominal obesity. This is often calculated by comparing the patient’s waist and hip measurements. But Civelek’s research suggest that, for at least some patients, it may not be that simple, with doctors using genetic testing to guide patients to good health.
“We found that among the hundreds of regions in our genomes which increase our propensity to accumulate excess fat in our abdomens, there are five which have an unexpected role,” said Yonathan Aberra, the lead author of the study and a PhD candidate at UVA’s Department of Biomedical Engineering, a joint program of the School of Medicine and School of Engineering. “To our surprise, these five regions decrease an individual’s risk for type 2 diabetes.”
In addition to producing surprising findings, Civelek’s research provides important new tools for his fellow researchers seeking to understand the complexities of gene variations. The sophisticated approach Civelek and his collaborators developed to identify the relevant variants and their potential effects will be useful for future research into metabolic syndrome and other conditions.
The tools could also prove invaluable in the development of new and better treatments for metabolic syndrome, the scientists say.
“We now need to expand our studies in more women and people from different genetic ancestries to identify even more genes that underlie the metabolically health obesity phenomenon,” Civelek said. “We plan to build on our findings to perform more experiments to potentially identify a therapeutic target.”
New Alzheimer’s research suggests that enhanced light sensitivity may contribute to ‘sundowning’, which is the worsening of symptoms late in the day, thereby spurring sleep disruptions thought to contribute to the disease’s progression.
Published in Frontiers in Aging Neuroscience, these new insights from UVA Health into the disruptions of the biological clock seen in Alzheimer’s could lead to new treatments and symptom management, the researchers say. For example, caregivers often struggle with the erratic sleep patterns caused by Alzheimer’s patients’ altered circadian rhythms. Light therapy, the new research suggests, might be an effective tool to help manage that.
Better understanding Alzheimer’s effects on circadian rhythms could have implications for prevention. Poor sleep quality in adulthood is a risk factor for Alzheimer’s, as brains at rest naturally cleanse themselves of amyloid beta proteins that are thought to form harmful tangles in Alzheimer’s.
“Circadian disruptions have been recognised in Alzheimer’s disease for a long time, but we’ve never had a very good understanding of what causes them,” said researcher Thaddeus Weigel, a graduate student working with Heather Ferris, MD, PhD. “This research points to changes in light sensitivity as a new, interesting possible explanation for some of those circadian symptoms.”
Alzheimer’s hallmark is progressive memory loss, to the point that patients can forget their own loved ones, but there can be many other symptoms, such as restlessness, aggression, poor judgment and endless searching. These symptoms often worsen in the evening and at night.
Ferris and her collaborators used a mouse model of Alzheimer’s to better understand what happens to the biological clock in Alzheimer’s disease. They essentially gave the mice “jet lag” by altering their exposure to light, then examined how it affected their behaviour. The Alzheimer’s mice reacted very differently to control mice.
The Alzheimer’s mice, the scientists found, adapted to a six-hour time change significantly more quickly than the control mice. This, the scientists suspect, is the result of a heightened sensitivity to changes in light. While our biological clocks normally take cues from light, this adjustment happens gradually – thus, jet lag when we travel great distances. Our bodies need time to adapt. But for the Alzheimer’s mice, this change happened abnormally fast.
The researchers initially thought this might be because of neuroinflammation. So they looked at immune cells called microglia that have become promising targets in developing better Alzheimer’s treatments. But the scientists ultimately ruled out this hypothesis, determining that microglia did not make a difference in how quickly mice adapted. (Though targeting microglia might be beneficial for other reasons.)
Notably, the UVA scientists also ruled out another potential culprit: “mutant tau,” an abnormal protein that forms tangles in the Alzheimer’s brain. The presence of these tangles also did not make a difference in how the mice adapted.
The researchers’ results ultimately suggest there is an important role for the retina in the enhanced light sensitivity in Alzheimer’s, and that gives researchers a promising avenue to pursue as they work to develop new ways to treat, manage and prevent the disease.
“These data suggest that controlling the kind of light and the timing of the light could be key to reducing circadian disruptions in Alzheimer’s disease,” Ferris said. “We hope that this research will help us to develop light therapies that people can use to reduce the progression of Alzheimer’s disease.”
The hepatitis B virus is estimated to cause about 820 000 deaths a year globally. It is one of the leading causes of liver cancer. One in 20 people in South Africa is infected with hepatitis B, yet few people know about or have been tested for the virus.
During a media briefing on Friday, organised by the Gastroenterology and Hepatology Association of Sub-Saharan Africa (GHASSA), a panel of experts stressed the need for urgent interventions to eliminate hepatitis.
There are clear solutions, the experts said: increase awareness, increase access to testing, and prevent childhood transmission through birth-dose vaccination and screening and treating pregnant women.
“We are way overdue on bringing hepatitis out of the shadows and into the light,” said Professor Mark Sonderup, from the University of Cape Town’s (UCT) academic hospital at Groote Schuur.
In South Africa, an estimated 2.8 million people have chronic hepatitis B. Liver cancer caused by hepatitis B is on the increase in Africa and worldwide. Besides cancer, the virus can cause serious liver disease.
Hepatitis B is transmitted through bodily fluids, including semen and blood. Antiretroviral treatment for chronic hepatitis B is available but only 22% of cases are diagnosed.
An estimated 76 000 children in South Africa under the age of five have hepatitis B. Children infected with hepatitis B are more likely to develop a chronic infection.
Children infect each other: the virus multiplies in the body without presenting symptoms and a drop of blood shared through play between children can transfer the virus.
“They walk around like ticking timebombs, spreading infections,” said Dr Neliswa Gogela, liver disease specialist at Groote Schuur. Hepatitis B is 100 times more infectious than HIV, said Gogela.
Children born in South Africa receive a hepatitis B vaccine at six, ten, and 14 weeks old. If a vaccine dose was given at birth, it would cut out the first six weeks during which a child could become infected. Birth-dose vaccines are government policy but it has not yet been implemented. Other African countries like Namibia have introduced birth-dose vaccines.
The virus can also be transmitted from mother to child during and after birth. Pregnant women should be screened as part of prenatal and antenatal healthcare services, said Professor Wendy Spearman, head of Hepatology at UCT. Those eligible for treatment should receive antiretrovirals to prevent transmission of the virus to the child.
Hepatitis B is a silent killer, said Professor Mashiko Sechedi, head of gastroenterology at Groote Schuur. The virus stays in the body and only presents symptoms when the disease is at an advanced stage. It can cause multifocal liver cancer which renders the liver inoperable. “In South Africa, we’re seeing young patients presenting with advanced disease,” said Sechedi.
Professor Eduard Jonas, a surgeon at Groote Schuur, said that half of the patients in Sub-Saharan Africa who are diagnosed with liver cancer die within two and a half months of diagnosis. Late diagnosis and lack of treatment capacity make liver cancer particularly deadly in Southern Africa, he said.
Screening and testing for hepatitis are not easily accessible, said Professor Geoff Dusheiko, from Kings College in London. Whereas anyone wanting to do an HIV test can go to any government clinic and receive a point-of-care rapid test, they cannot do so for hepatitis B.
Rapid tests for hepatitis B are available but have not been rolled out by the government, so the only way to do a hepatitis test through public health facilities is to take blood, which is sent to a laboratory for testing.
While HIV, malaria and TB have attracted significant attention and funding, hepatitis has not. “We need people living with hepatitis B demanding access to treatment,” said Spearman.
Circumcision rates in South Africa have increased dramatically over the last decade with 62.5% of males aged 15 to 49 who were circumcised as of 2022. PHOTO: Rodger Bosch
There is compelling scientific evidence that Voluntary Male Medical Circumcision (VMMC) is both safe and significantly reduces a man’s risk of becoming infected with HIV. While there can also be some protection from traditional circumcision, the protective effect of medical circumcision is thought to be much greater. The World Health Organization (WHO) has recommended medical circumcision for HIV prevention since 2007.
Circumcision rates in South Africa have increased dramatically over the last decade. According to estimates from Thembisa, the leading mathematical model of HIV in South Africa, 62.5% of males aged 15 to 49 were circumcised as of 2022. In 2012, this number stood at 38.8%. Experts ascribe some of the reduction in the country’s rate of new HIV infections to the massive circumcision drive over the last decade.
But the choice between medical, traditional, or no circumcision is often about much more than HIV risk. For one thing, traditional circumcision has great cultural meaning for some groups.
‘From boyhood to manhood’
Spotlight visited Lwazi Mfeka* at his ibhoma (traditional hut) during his last week at an initiate school in the Eastern Cape this winter. The first-year Walter Sisulu University student asked to remain anonymous for fear of victimisation, as talking openly about initiation is taboo in many rural communities.
He said leaving his ibhoma on the last day of his tenure as an initiate is a moment that will forever be etched in his mind. Not only did this signal the end of a “challenging” three-week period at the school, but it was also a symbolic moment where he says he has graduated from boyhood to manhood.
Mfeka said he was supposed to have undergone the ritual in December last year, but due to a bereavement in his family, he couldn’t. “At varsity, I was often mocked and isolated because I was still a ‘boy’. This bothered me a lot and I couldn’t wait to come here (to the mountain) and finally become a man,” he said.
He admits he was gripped by fear in the months leading up to his initiation.
“For starters, many young boys die while undergoing the custom and I didn’t want to add to the numbers. But, fortunately, my dad chose an ingcibi (traditional surgeon) with a good track record. I first had to go and get tested by a doctor for chronic illnesses such as HIV and TB as I had to present a medical certificate to the ingcibi before being circumcised. At the initiation school, everything was done according to the rules. After each cut, the spear gets sanitised to avoid any spread of infections,” Mfeka said.
Botched circumcisions
Mfeka’s fears are not without merit. In recent years, traditional male circumcision has often made headlines for all the wrong reasons, with the lives of young men lost due to botched or unhygienic circumcisions.
According to Mamnkeli Ngam, spokesperson for the Eastern Cape Department of Cooperative Governance and Traditional Affairs, in the 2022 winter initiation season, 11 of 10 794 boys who underwent traditional circumcision in the province died, while in the summer initiation season, 23 of 51 601 died. Ngam says around 20 000 boys went into the mountains to undergo traditional circumcision this winter (2023).
He told Spotlight that some fly-by-night ingcibis, desperate to make a quick buck, are the ones giving the custom a bad name. He says that assisted by the local chiefs and the police, they have been clamping down on illegal initiation schools and arresting bogus traditional surgeons.
“During the period between 1 June to 20 July, nine bogus traditional surgeons have been arrested in the Eastern Cape,” Ngam said.” We have been conducting safety campaigns ahead of the winter circumcision season to educate communities. Circumcising boys without parental consent [and] not having undergone medical examination to perform the procedure is against the law.”
Nkosi Mpumalanga Gwadiso, the Eastern Cape House of Traditional and Khoisan Leaders’ chair, told Spotlight that parents need to be involved throughout the process. “Often, parents leave everything to the amakhankatha (traditional nurses). That’s where things go wrong. As chiefs, we always emphasise the importance of parental involvement from day one until the initiates come back home safely. Some traditional nurses are the reason things go wrong because they neglect the initiates and go drinking. It is therefore the responsibility of the fathers to ensure that they visit the initiation schools regularly and monitor everything,” Gwadiso said.
While numbers vary widely and we haven’t been able to get a full picture, we understand that initiation schools can admit around 100 initiates during each of the winter and summer circumcision seasons. Our informal survey of several initiation camps in the former Transkei suggests the cost is typically around R300.
The medical alternative
While medical male circumcision is a generally available alternative to traditional circumcision, its provision in the Eastern Cape is influenced by cultural factors. For example, according to Eastern Cape Provincial Health Department spokesperson, Yonela Dekeda, the department does not conduct open marketing or demand creation in the communities/public “due to cultural dynamics within the province”.
“Medical Male Circumcision services are actually confined within the health facility level. Therefore, intake depends on the walk-ins, not on demand creation or promoting of the MMC services,” Dekeda said. “MMC is the choice of individual families. However, as the department, we are ensuring that all the designated MMC sites are well equipped with necessary MMC equipment, including training of clinicians such as medical doctors, clinical associates, and professional nurses to provide quality voluntary medical male circumcision services.”
Despite the lack of promotion, some young men, such as Bandile Macetywa*, have opted to go the medical route. He asked that we not use his real name for fear of victimisation from people who disapprove of his decision not to be circumcised in the traditional manner.
Speaking to Spotlight, the 20-year-old from Cofimvaba in the Eastern Cape said he pleaded with his parents, who are staunch traditionalists, to do the custom the medical way. “I know I disappointed my parents, especially my father, but at the end of the day, it was about my safety. I was happy when they respected my decision,” he said.
However, Mecatywa says he is all too aware of the discrimination that awaits him in society. “There are already naysayers. But I’m just glad the whole process went well. For Pete’s sake, we are in 2023. People are free to choose where they get circumcised. Some people had the guts to tell me to my face that I deserved to be abducted and circumcised again the traditional way?” he said.
Mecetywa believes many lives will be saved if rural communities can be educated to accept medical male circumcision. “It is much safer with [fewer] risks of getting infected while undergoing it. I am not saying traditional male circumcision is wrong. But why do initiates continue to die or have botched operations if things are done the right way,” he asked.
While the department does not actively promote medical circumcision, and while Mecetywa is clearly very aware of being in a minority, there are in fact significant numbers of medical circumcisions being conducted in the Eastern Cape. According to Dekeda, 14 637 were performed in the province in 2022, while 14 300 have been performed so far this year.
Medical male circumcision is an elective procedure that is widely available in the public sector, often provided via NGOs. The process typically involves counselling, a pre-assessment to check for anything that may hamper a client’s ability to be circumcised, post-operative care, and follow-up visits. Clients will typically also be offered an HIV test.
VMMC in the Western Cape
Meanwhile, in the Western Cape, the Department of Health and Wellness in collaboration with the City of Cape Town and the Department of Cultural Affairs and Sport has implemented an initiation consent form as a mechanism to uphold ethics. It includes medical screening that helps minimise and mitigate potential risks.
Western Cape Department of Health spokesman Mark Van der Heever told Spotlight, “The initiation consent form is further reviewed to enable alignment to developments as these emerge. Training and capacitation of traditional surgeons is a key element to strengthening partnership following a whole of government and whole of society approach.”
Van der Heever says since 2020, 274 circumcisions were performed by a Medical Officer invited by the traditional healers to perform the circumcisions. A total of 131 977 medical male circumcisions, according to Van der Heever, were performed at the Western Cape health facilities since 2013, with 13 105 performed just last year.
The rest of the stats are as follows:
2013 – 12 581
2014 – 15 990
2015 – 14 131
2016 – 11 982
2017 – 15 127
2018 – 14 557
2019 – 18 000
2020 – 5 750 (COVID)
2021 – 10 754 (COVID)
2022 – 13 105
Van der Heever adds that between April and March 2023, Medical Male Circumcision was reported at 130 public health sites and a total of 12 259 circumcisions were performed across the province.
“The province also has two Men’s Health Clinics (in Karl Bremer and Elsies River). With the intention of increasing access to services, we are in discussions to upskill clinicians to enable service provision at health facilities. Current service provision is based on roving teams in both the metro and rural districts, which limit access to availability of the team.”
