Tag: ageing

Gut Microbiome Changes are Linked to Ageing and Longevity

Ageing in humans is marked by compositional changes in the gut microbiome that become more unique later in life.

Researchers from the Institute for Systems Biology (ISB) analysed gut microbiome, phenotypic and clinical data from over 9000 people across three independent cohorts. Health and survival outcomes were tracked from longitudinal data from a cohort of over 900 community-dwelling older individuals (78-98 years old).

The researchers found that, starting in mid-to-late adulthood, gut microbiomes became increasingly unique as individuals aged, corresponding with a steady decline in the abundance of core bacterial genera common across humans.

Strikingly, while microbiomes became increasingly unique to each individual in healthy aging, the metabolic functions the microbiomes were carrying out shared common traits. Gut microbiome uniqueness was highly correlated with several microbially-derived metabolites in blood plasma. One of them, tryptophan-derived indole, has been shown to extend lifespan in mice. Another metabolite, phenylacetylglutamine, showed the strongest association with uniqueness, and is known to be highly elevated in the blood of people over 100.

“This uniqueness signature can predict patient survival in the latest decades of life,” said study leader Dr Tomasz Wilmanski, who led the study. Healthy individuals aged around 80 showed continued microbial drift toward a uniqueness, but this drift was not seen in less healthy individuals of the same age.

“Interestingly, this uniqueness pattern appears to start in mid-life—40-50 years old—and is associated with a clear blood metabolomic signature, suggesting that these microbiome changes may not simply be diagnostic of healthy aging, but that they may also contribute directly to health as we age,” Wilmanski said. Indoles are known to reduce inflammation in the gut, for example, and chronic inflammation is believed to drive age-related morbidities.

“Prior results in microbiome-aging research appear inconsistent, with some reports showing a decline in core gut genera in centenarian populations, while others show relative stability of the microbiome up until the onset of aging-related declines in health,” said co-corresponding author, microbiome specialist Dr Sean Gibbons. “Our work, which is the first to incorporate a detailed analysis of health and survival, may resolve these inconsistencies. Specifically, we show two distinct aging trajectories: (1) a decline in core microbes and an accompanying rise in uniqueness in healthier individuals, consistent with prior results in community-dwelling centenarians, and (2) the maintenance of core microbes in less healthy individuals.”

This analysis highlights the fact that the adult gut microbiome continues to develop with advanced age in healthy individuals, but not in unhealthy ones, and that microbiome compositions associated with health in early-to-mid adulthood may not be compatible with health in late adulthood.

Source: Medical Xpress

Journal information: Gut microbiome pattern reflects healthy ageing and predicts survival in humans, Nature Metabolism (2021). DOI: 10.1038/s42255-021-00348-0

Europe’s Oldest Living Person, 116, Survives COVID

A 116 year old French nun who is Europe’s oldest living person has survived COVID after testing positive.

French nun Sister Andrée had tested positive for COVID in her retirement home in Toulon, but had remained symptom-free. Most of the 88 residents at the home contracted the virus, 10 of whom died. 

Sister Andrée, who is blind and in a wheelchair, said that her main complaint was the solitude necessitated by being confined to her room.
“I didn’t even realise I had it,” she told Var-Matin newspaper:

David Tavella, a spokesperson for the nursing home, told the newspaper that she had no fear of the virus.

“She didn’t ask me about her health but about her routine. She wanted to know for example if the meal and bed times were going to change. She showed no fear of the illness, in fact she was more worried about the other residents,” Mr Tavella said.

When asked by France’s BFM Television if she had been scared of having COVID, she responded: “No, I wasn’t scared because I wasn’t scared to die … I’m happy to be with you, but I would wish to be somewhere else – join my big brother and my grandfather and my grandmother.”

In addition to being Europest oldest living person, she is also the world’s second oldest living person. The oldest living person in the world is Kane Tanaka in Japan, who turned 118 on January 2. Having lived through the First World War as a child, Sister Andrée will turn 117 on Thursday.

Source: The Guardian

Legendary Singer Tony Bennett Diagnosed with Alzheimer’s

Music legend Tony Bennett, 94, revealed in an interview that he was diagnosed with Alzheimer’s disease 4 years ago.

The singer’s career has spanned seven decades, he had continued his initial success in the 1950s across multiple genres, becoming a hit with the MTv generation, and in more recent years collaborating with popular artists like Amy Winehouse and Lady Gaga.

Alzheimer’s disease is an age-related, irreversible neurodegenerative condition. In more than 90% of patients, it begins after age 65, although it can occur as early as in the 30s. It is marked by memory loss and confusion that seem like the normal cognitive decline of older age, but it is more rapid and severe, eventually resulting in death. As people live longer and the risks of developing this disease increase with age, the burden of this disease is expected to increase in the future. In the US, the number of people with Alzheimer’s is expected to nearly triple from 5.5 million to 14 million by 2060.

Mr Bennett has been able to work over the past four years but the toll is perceptible. He still recognises his family members but his short-term and long-term memory have drastically deteriorated. Interviewer John Colapinto noted Mr Bennett gazing at his lavishly illustrated book, “Tony Bennett Onstage and in the Studio” (2018). “He stared into its pages not with the air of warm reminiscence but like a man struggling to recall why these images seemed familiar.” His wife, Susan, added that Mr Bennett is “not always sure where he is or what is happening around him. Mundane objects as familiar as a fork or a set of house keys can be utterly mysterious to him.”

Over the past two years, Mr Bennett recorded a second album of duets with Lady Gaga, a follow-up to the hit album with Gaga in 2014. While he had been known to be a “meticulous and hard-driving perfectionist in the studio,” Mr Bennett was much more subdued. speaking rarely, his words coming haltingly and seeming lost or bewildered. Gaga, who considers Mr Bennett to be “an incredible mentor, and friend, and father figure” is seen breaking down in tears as Tony sings a solo passage of a love song.

The album is due to be released this spring, but Mr Bennett will be unable to do promotional interviews. Mr Bennett, together with his wife and son (who is also his manager) decided to break the news, in the hopes that as many fans as possible know about what will likely be his final record. The neurologist who diagnosed Bennett in 2016,  Gayatri Devi, MD, said: “He is doing so many things, at 94, that many people without dementia cannot do. He really is the symbol of hope for someone with a cognitive disorder.”

Source: MedPage Today

Cannabis can Lower Hypertension in Older Adults

Adding to a growing body of evidence as to its health benefits, medical cannabis may lower blood pressure in older adults, according to research from Ben-Gurion University of the Negev (BGU) and its affiliated Soroka University Medical Center.

This is the first such study to investigate cannabis’  effect on blood pressure, heart rate and metabolic parameters in hypertensive adults 60 and older.

“Older adults are the fastest growing group of medical cannabis users, yet evidence on cardiovascular safety for this population is scarce. This study is part of our ongoing effort to provide clinical research on the actual physiological effects of cannabis over time,” said Dr Ran Abuhasira, BGU Faculty of Health Sciences and BGU-Soroka Cannabis Clinical Research Institute

Before and three months after beginning medical cannabis therapy, patients in the study were evaluated using 24-hour ambulatory blood pressure monitoring, ECG, blood tests, and body measurements. Patients ingested cannabis either orally in the form of oil extracts or by smoking.

The findings included a significant drop in 24-hour systolic and diastolic blood pressure values, with the lowest point occurring three hours after ingesting cannabis. Both daytime and nighttime reductions in blood pressure were observed, with more greater changes at night. Higher nighttime than daytime blood pressure may also raise the risk of Alzheimer’s disease, so lowering it at night may offer that benefit.

The pain relief from taking cannabis, often a reason for prescriptions, may also have resulted in a reduction of blood pressure, the BGU researchers postulated.

“Cannabis research is in its early stages and BGU is at the forefront of evaluating clinical use based on scientific studies,” said Doug Seserman, chief executive officer of American Associates, BGU. “This new study is one of several that has been published recently by BGU on the medicinal benefits of cannabis.”

Source: News-Medical.Net

Journal information: Abuhasira, R., et al. (2021) Cannabis is associated with blood pressure reduction in older adults – A 24-hours ambulatory blood pressure monitoring study. European Journal of Internal Medicine.doi.org/10.1016/j.ejim.2021.01.005.

APLS1 Inhibitors Eliminate Senescent Cells to Ameliorate Ageing

A new technique has been developed to eliminate senescent cells that are involved in many age-related diseases, according to a study by researchers at the University of Tokyo.

As ageing progresses, cancers emerge, motor function declines through muscle loss, and metabolic disorders occur due to adipose tissue atrophy. Senescent cells accumulating in organs are behind many of these problems; their telomeres having shortened through divisions as a result of multiple stresses and now at their replication limit, they now no longer function effectively. Previous research using genetic engineering to knock out senescent cells in mice was able to put the onset of age-related diseases such as arteriosclerosis and renal damage, and extended life expectancy. However, the research did not yield a drug which could be given as a treatment.

To tackle this problem, the researchers created a way to produce large numbers of purified senescent. cells to search for genetic targets for drugs. One of the ways they found involved GLS1, a gene involved in glutamine. On testing with GLS1 inhibitors, senescent cells were vulnerable due to damage to the lysosomal membrane and lower intracellular pH. Lysosomes are organelles which produce enzymes to destroy defunct cell parts, bacteria and viruses if needed, and the cell itself if apoptosis is triggered. They also have an essential role in the regulation of intracellular pH, and are very acidic, having to be protected from the rest of the cell by a membrane. Analysing the dynamics of lysosomes, the team found that damage to the lysosomal membranes in senescent cells decreases intracellular pH.

When they administered GLS1 inhibitors to old mice, knocking out senescent cells, their ageing was significantly improved. The symptoms of obese diabetes, arteriosclerosis, and fatty liver disease were ameliorated. GLS1 inhibitors are already being used in trials as cancer treatments.
“We hope that innovative anti-aging therapies and treatments for geriatric diseases will be developed that can remove senescent cells by treatment with GLS1 inhibitors,” said Professor Nakanishi.

Source: News-Medical.Net

Journal information: Johmura, Y., et al. (2021) Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders. Science. doi.org/10.1126/science.abb5916.

New Study Has Good and Bad News on TIAs

There is both good and news on transient ischaemic attacks (TIAs) from a more than six-decade long study: TIAs are indeed harbingers of strokes, but also the incidence of post-TIA strokes has been falling over the decades.

A TIA is defined as a passing episode of neurologic dysfunction due to the focal brain, spinal cord, or retinal ischaemia, without acute infarction or tissue injury. The results were derived from the Framingham Heart Study had 14 059 participants and ran for over six decades, allowing for a more-complete picture of strokes that happen after a TIA. Of the participants, 435 had a TIA; these were compared against a second group of 2175 participants who did not have a TIA.

Even after accounting for other risk factors such as hypertension or diabetes, people who had experienced a TIA had a 4.5 to five times greater chance of a stroke. Study lead author Vasileios-Arsenios Lioutas, MD, said that the results show a need for intensive follow-up of TIA : “According to our findings, people continue to have a high risk of stroke for a sustained time after they’ve had a TIA. Therefore, one shouldn’t think that the high-risk period is just in the first 90 days after the attack and then one can relax. It seems these patients should be followed closely over time, keeping in mind that they are at risk for stroke and paying close attention to controlling their cardiovascular risk factors.”

The 66 years of study data was broken into three epochs. One- and five-year risks of post-TIA stroke in the 2000-2017 epoch were 7.6% and 16.1%, compared to 23.9% and 35.5% during the earliest epoch, from 1948 to 1985.

Sudha Seshadri, MD, professor of neurology at The University of Texas Health Science Center at San Antonio, said: “We examined 66 years of follow-up from Framingham participants, which allowed us to study trends over time. We can see that starting in the very early years of the Framingham study, the 1950s, moving on to the most recent times, the risk of subsequent stroke went down a lot.”

Source: News-Medical.Net

Journal information: Lioutas, V-A., et al. (2021) Incidence of Transient Ischemic Attack and Association With Long-term Risk of Stroke. JAMA.doi.org/10.1001/jama.2020.25071.

Mediterranean-type Diets Protect Against Parkinson’s Disease

Researchers at the University of British Columbia have shown that the Mediterranean diet and another diet based on it, have a strong link in protecting against Parkinson’s disease (PD). 

These two diets had previously been shown that they could protect against other neurodegenerative diseases. The Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) diet combines aspects of the Mediterranean diet and the DASH diet which protects against hypertension. The MIND diet emphasises consumption of berries, as research shows that they protect against mental decline, eating leafy greens and poultry. The MIND diet also mostly does away with potato, milk and fruit (excluding berries).

Senior author Dr Silke Appel-Cresswell said, “There is a lack of medications to prevent or delay Parkinson’s disease yet we are optimistic that this new evidence suggests nutrition could potentially delay onset of the disease.”
Following the diets delayed the average onset of PD by 17.4 years in women, and 8.4 years in men.

Since PD already has a notable sex difference, with 60% of sufferers being men, despite their shorter average lifespan, the sex difference in response to the diets opens new avenues of research
“It drives home the connection between the gut and the brain for this disease,” Dr Brett Finlay said. “It also shows it’s not just one disease that healthy eating can affect, but several of these cognitive diseases.”

Source: Medical Xpress

Journal information: Avril Metcalfe‐Roach et al, MIND and Mediterranean Diets Associated with Later Onset of Parkinson’s Disease, Movement Disorders (2021). DOI: 10.1002/mds.28464

Mid-life Exercise Positively Shapes Late-life Brain Structure

That exercise in one’s middle years benefits health in later life is perhaps no surprise given our current understanding of its benefits, but and MRI study has shown to influence the brain’s structure in later years.

Using MRI scans, high levels (150 minutes per week or more) of self-reported moderate-to-high physical activity were associated with reduced risk of lacunar infarct in late life (OR 0.68, 95% CI 0.46-0.99) and more intact white matter integrity.

“Our study suggests that getting at least an hour and 15 minutes of moderate-to-vigorous intensity physical activity a week or more during midlife may be important throughout your lifetime for promoting brain health and preserving the actual structure of your brain,” said Priya Palta, PhD, of Columbia University Irving Medical Center. “In particular, engaging in more than 2 and a half hours of physical activity per week in middle age was associated with fewer signs of brain disease.”

There has been mixed evidence linking physical activity to brain measures or improvements in cognitive function. PhDs Nicole Spartano, of Boston University School of Medicine, and Leonardo Pantoni, MD, of University of Milan, noted in an accompanying editorial that the “most consistent evidence for the protective effect of physical activity against dementia risk has been reported to be leisure time physical activity, and it is unclear whether there is benefit to other types of physical activity that may be less ‘enriching.'”

“It is possible that future work will uncover the requirement that physical activity interventions to reduce dementia risk actually have an enriching element, such as in leisure-time activities, rather than be strictly rote, mechanical movement,” Spartano and Pantoni added.

Recruiting 1 604 individuals with a mean baseline age of 54, the participants had five examinations over 25 years and MRI at a mean age of 72. At baseline (1987-1989) and 25 years later, participants had their moderate-to-vigorous physical activity assessed in a questionnaire. 

At midlife, 11% had low levels of moderate-to-high intensity activity (1 to 74 minutes a week), 16% middle levels (75 to 149 minutes a week), and 39% high levels (150 minutes a week or more), with the remainder reporting none.

High moderate-to-vigorous midlife activity was associated with better white matter integrity in late life, compared with no moderate-to-vigorous midlife activity, but there was no association with grey matter volume.

While the risk of lacunar infarcts were lower with more intense midlife activity, risk of cortical infarcts or subcortical microhemorrhage were not. “The associations of greater levels of mid-life physical activity with fewer lacunar (but not cortical) infarcts and greater white matter microstructural integrity suggest cerebrovascular mechanisms are primarily at play,” Palta and colleagues wrote.

When adjusted for vascular risk factors, the association of midlife physical activity to lacunar infarcts was weakened, but the association with white matter microstructure. The editorialists said that it implies that “evidence from this study supports a hypothesis that the mechanisms linking physical activity and the brain are likely multi-dimensional, including mechanisms other than simply improving cerebrovascular health.” 

Late-life moderate-to-vigorous physical activity also was associated with most brain measures compared with no moderate-to-vigorous activity, but as this was a prospective study that spanned decades, the “association between midlife physical activity levels and later-life brain imaging features makes a much stronger case for causality than does the same relationship when measured only in late life,” the researchers noted.

The study had several limitations, which included using self-reported data, did not include non leisure-related activity, and participant attrition.

Source: MedPage Today

Journal information: Source Reference: Palta P, et al. A prospective analysis of leisure-time physical activity in midlife and beyond and brain damage on MRI in older adults, Neurology 2020; DOI: 10.1212/WNL.0000000000011375.

Benefits of Cutting Cholesterol for Elderly Increase with Age

A pair of new studies in The Lancet found that the effects of low-density lipoprotein (LDL) lowering agents reduced the number of serious cardiovascular events in geriatric patients.

Taking data on over 90 000 individuals in Denmark, an observational study followed patients for 7.7 years, with LDL cholesterol levels as well as first heart attacks or strokes recorded.

The researchers found that people aged 70-100 without a previous cardiovascular event benefited more from taking cholesterol-lowering medications in terms of preventable cardiovascular events.

People aged 80-100 had the highest incidence of heart attacks, at 8.5 per 1000 person-years.

Børge Nordestgaard, joint author of the first study, of the Copenhagen University Hospital, said, “Our study provides further evidence for the cumulative burden of LDL cholesterol over a person’s lifetime and the progressive increase in risk for heart attack and cardiovascular disease with age. With the proportion of people living beyond 70 years of age worldwide rapidly increasing, these data point to the huge potential for primary prevention strategies aimed at lowering LDL cholesterol levels to reduce the population burden of heart disease. The findings should guide decision making about whether older individuals will benefit from statin therapy.”

A separate review and meta-analysis revealed that cholesterol-lowering therapies are as effective as preventing heart attacks in older patients as they are in younger ones. Analysing data from 29 randomised controlled trials, they found that for every reduction of 1mmol/L of HDL cholesterol, the relative risk of major cardiovascular events in patients over 75 years was reduced by 26%. For patients under 75 years, the reduction was 15% per 1mmol/L of HDL-cholesterol.

Source: HCP Live

New Drug Relieves Rheumatoid Arthritis Pain

A new drug, otilimab, has shown effectiveness in treating rheumatoid arthritis (RA). Otilimab is a human monoclonal antibody which inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF is a large driver of immune-mediated inflammatory conditions.

The drug is currently being tested on its ability to suppress inflammation, tissue damage and pain in RA sufferers.

A multicentre, dose-ranging trial conducted with the drug. Participants were administered subcutaneous injections with one of five different dosages of otilimab (22.5 mg, 45 mg, 90 mg, 135 mg, or 180 mg) or placebo weekly for five weeks. Thereafter, they received injections once every two weeks for one year. The results showed a rapid reduction in tenderness and swelling, and a very high reduction in pain.

The study was unusual in that it offered an escape arm. It is often difficult to recruit participants when they know they may be receiving a dummy injection, and so if, after 12 weeks the participants  on the placebo arm derived no benefit, they were transferred to the highest dose arm of 180mg.

Source: Medical Xpress

Journal information: Christopher D Buckley et al, Efficacy, patient-reported outcomes, and safety of the anti-granulocyte macrophage colony-stimulating factor antibody otilimab (GSK3196165) in patients with rheumatoid arthritis: a randomised, phase 2b, dose-ranging study, The Lancet Rheumatology (2020). DOI: 10.1016/S2665-9913(20)30229-0