Category: Ageing

Categories : Ageing GenderTags :

Losing their Y Chromosome Shortens Men’s Lifespans

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DNA repair
Source: Pixabay/CC0

As many men age, they lose their Y chromosome, which causes heart muscle to scar and can lead to deadly heart failure, new research from the shows. The finding, which appears in Science, may help explain why men die, on average, several years younger than women.

University of Virginia School of Medicine researcher Kenneth Walsh, PhD, says the new discovery suggests that men who suffer Y chromosome loss – estimated to include 40% of 70-year-olds – may particularly benefit from an existing drug that targets dangerous tissue scarring. The drug, he suspects, may help counteract the harmful effects of the chromosome loss – effects that may manifest not just in the heart but in other parts of the body as well.

On average, women live five years longer than men in the United States. The new finding, Prof Walsh estimates, may explain nearly four of the five-year difference.

“Particularly past age 60, men die more rapidly than women. It’s as if they biologically age more quickly,” said Prof Walsh. “There are more than 160 million males in the United States alone. The years of life lost due to the survival disadvantage of maleness is staggering. This new research provides clues as to why men have shorter lifespans than women.”

Many men begin to lose their Y chromosome in a fraction of their cells as they age, especially in smokers. The loss occurs predominantly in cells that undergo rapid turnover, such as blood cells. However, Y chromosome loss does not occur in male reproductive cells, so it is not inherited by the children of men who exhibit Y chromosome loss. It has been observed that men who suffer Y chromosome loss are more likely to die at a younger age and suffer age-associated maladies such as Alzheimer’s disease. This new research however is believed to be the first hard evidence that the chromosome loss harms men’s health.

Walsh and his team used CRISPR gene-editing technology to develop a special mouse model to better understand the effects of Y chromosome loss in the blood. The loss accelerated age-related diseases, made the mice more prone to heart scarring, leading to earlier death. But more than just the results of inflammation, there was complex series of responses in the immune system, leading to fibrosis throughout the body. This tug-of-war within the immune system, the researchers believe, may accelerate disease development.

The scientists also looked at the effects of Y chromosome loss in human men. They conducted three analyses of data compiled from the UK Biobank, a massive biomedical database, and found that Y chromosome loss was associated with cardiovascular disease and heart failure. As chromosome loss increased, the scientists found, so did the risk of death.

The findings suggest that targeting the effects of Y chromosome loss could help men live longer, healthier lives. One treatment option might be a drug, pirfenidone, approved in the US for the treatment of idiopathic pulmonary fibrosis. The drug is also being tested for the treatment of heart failure and chronic kidney disease, two conditions for which tissue scarring is a hallmark. Based on his research, Walsh believes that men with Y chromosome loss could respond particularly well to this drug, and other classes of antifibrotic drugs that are being developed, though more research will be needed to determine that.

At the moment, doctors have no easy way to determine which men suffer Y chromosome loss. Prof Walsh’s collaborator Lars A. Forsberg, of Uppsala University in Sweden, has developed an inexpensive polymerase chain reaction (PCR) test that can detect Y chromosome loss, but the test is largely confined to his and Prof Walsh’s labs. Prof Walsh, however, can foresee that changing: “If interest in this continues and it’s shown to have utility in terms of being prognostic for men’s disease and can lead to personalised therapy, maybe this becomes a routine diagnostic test,” he said.

“The DNA of all our cells inevitably accumulate mutations as we age. This includes the loss of the entire Y chromosome within a subset of cells within men. Understanding that the body is a mosaic of acquired mutations provides clues about age-related diseases and the aging process itself,” said Walsh, a member of UVA’s Department of Biochemistry and Molecular Genetics. “Studies that examine Y chromosome loss and other acquired mutations have great promise for the development of personalised medicines that are tailored to these specific mutations.”

Source: University of Virginia Health System

Categories : Ageing Cardiovascular DiseaseTags :

Type of Macular Degeneration Linked to Cardiovascular Disease

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Credit: National Eye Institute

Patients with a certain subtype of age-related macular degeneration (AMD) are at significant risk for cardiovascular disease and stroke, according to new research published in Retina.

“For the last three decades researchers have suggested an association between AMD and cardiovascular disease, but there has been no conclusive data on this until now. Our retinal team answered this important question by focusing on two different varieties of AMD that can be seen with advanced retinal imaging. We discovered that only one form of AMD, that with subretinal drusenoid deposits, is tightly connected to high-risk vascular diseases, and the other form, known as drusen, is not,” explained lead author R. Theodore Smith, MD, PhD, Professor at Mount Sinai. “If ophthalmologists diagnose or treat someone with the specific subretinal drusenoid deposits form of AMD, but who otherwise seems well, that patient may have significant undetected heart disease, or possibly carotid artery stenosis that could result in a stroke. We foresee that in the future, as an improved standard of care, such patients will be considered for early referral to a cardiologist for evaluation and possibly treatment.”

AMD is the leading cause of visual impairment and blindness over the age of 65. Drusen is one major form of early AMD: small yellow cholesterol deposits form in a layer under the retina, depriving it of blood and oxygen, leading to vision loss. Drusen formation can be slowed by appropriate vitamin supplementation.

The other major form of early AMD is the presence of subretinal drusenoid deposits (SDD), which is lesser known, which needs advanced retinal imaging to detect. These deposits are also made of fatty lipids and other materials, but form in a different layer beneath the light sensitive retina cells, where they are also associated with vision loss. There is no known treatment for SDD at present.

Mount Sinai researchers analysed 126 patients with AMD, using optical coherence tomography (OCT) which captures high-resolution cross-sectional scans of the retina. Patients also answered health history questionnaires. Of the patients on the study, 62 had SDD and 64 had drusen; 51 of the 126 total patients (40%) reported having cardiovascular disease or a past stroke, and most (66%) of those patients had SDD. By contrast, of the 75 patients who did not have known heart disease or stroke, relatively few (19%) had SDD. The odds of patients with cardiovascular disease or stroke having SDD was three times than in patients without.

The researchers suggested that the underlying cardiovascular disease likely compromises blood circulation in the eye, leading to the SDDs beneath the retina.

“We believe poor ocular circulation that causes SDDs is a manifestation of underlying vascular disease. This has important public health implications and can facilitate population screening and disease detection with major impact,” explained author Jagat Narula, MD, PhD, Associate Dean of Global Affairs and Professor of Medicine (Cardiology), and Radiology, at the Icahn School of Medicine at Mount Sinai. “Seen in an eye clinic, such patients should be prompted to see a cardiologist. On the other hand, if clinically substantiated in prospective studies, SDDs could emerge as a risk marker for underlying vascular disease in asymptomatic patients in primary care or a cardiology clinic. The temporal relationship between SDDs and macrovascular disease will also need to be established in prospective studies which are currently in progress.”

Analysis of patient blood samples revealed genetic risk factors may also play a role in SDD cases in addition to vascular causes. Specifically, they found that the ARMS2 gene acted independently of vascular disease to cause SDD in some patients.

“This study further demonstrates that AMD is not a single condition or an isolated disease, but is often a signal of systemic malfunction which could benefit from targeted medical evaluation in addition to localised eye care,” noted Richard B. Rosen, MD, Chief of the Retina Service for the Mount Sinai Health System. “It helps bring us one step closer to unraveling the mystery of this horrible condition which robs so many patients of the pleasure of good vision during their later years. “

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine

Categories : Ageing HIVTags :

HIV Infection Found to Accelerate Ageing Process

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HIV Infecting a T9 Cell. Credit: NIH

Within just two to three years of infection, HIV causes an “early and substantial” impact on ageing in infected people, accelerating epigenetic changes and telomere shortening associated with normal ageing, according to a study in iScience.

The findings suggest that new HIV infection may act to reduce an individual’s life span by five years compared to an uninfected person.

“Our work demonstrates that even in the early months and years of living with HIV, the virus has already set into motion an accelerated ageing process at the DNA level,” said lead author Elizabeth Crabb Breen, a professor emerita at UCLA. “This emphasises the critical importance of early HIV diagnosis and an awareness of ageing-related problems, as well as the value of preventing HIV infection in the first place.”

In previous studies, HIV and antiretroviral treatment has been observed to accelerate age-related conditions such as cardiovascular and renal disease, grail and cognitive impairment.

Researchers analysed stored blood samples from 102 men collected six months or less before they became infected with HIV and again two to three years after infection. They compared these with matching samples from 102 non-infected age-matched men taken over the same time period. All the men were participants in the Multicenter AIDS Cohort Study, an ongoing US study initiated in 1984.

The study examined how HIV affects epigenetic DNA methylation. Epigenetic changes are those made in response to the influence of outside factors such as disease that affect how genes behave without changing the genes themselves.

Five epigenetic measures of ageing were analysed – four of them are epigenetic ‘ clocks’, each of which uses a slightly different approach to estimate biological age acceleration in years, relative to chronologic age. The fifth measure assessed telomere length, which shorten with age and cell divisions.

Compared to non-infected controls, HIV-infected individuals showed significant age acceleration in each of the four epigenetic clock measurements – ranging from 1.9 to 4.8 years – as well as telomere shortening over the period beginning just before infection and ending two to three years after, in the absence of highly active antiretroviral treatment.

“Our access to rare, well-characterised samples allowed us to design this study in a way that leaves little doubt about the role of HIV in eliciting biological signatures of early ageing,” said senior author Professor Beth Jamieson. “Our long-term goal is to determine whether we can use any of these signatures to predict whether an individual is at increased risk for specific ageing-related disease outcomes, thus exposing new targets for intervention therapeutics.”

Study limitations included having only men as participants, with few non-white participants. The sample size was also too small to take into consideration later effects of highly active antiretroviral treatment or to predict clinical outcomes. Additionally, there presently is no consensus on what is normal ageing or how to define it, the researchers wrote.

Source: UCLA

Categories : Ageing VaccinesTags : 1 Comment

Flu Jab May Protect Against Developing Alzheimer’s

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Old man
Source: JD Mason on Unsplash

In a study with nearly 2 million older adults, those who received at least one influenza vaccine were 40% less likely than their non-vaccinated peers to develop Alzheimer’s disease over four years of follow-up, according to a new study from UTHealth Houston.

An early online version of the paper detailing the findings is available in advance of its publication in the Journal of Alzheimer’s Disease in August.

“We found that flu vaccination in older adults reduces the risk of developing Alzheimer’s disease for several years. The strength of this protective effect increased with the number of years that a person received an annual flu vaccine – in other words, the rate of developing Alzheimer’s was lowest among those who consistently received the flu vaccine every year,” said first author Avram S. Bukhbinder, MD. “Future research should assess whether flu vaccination is also associated with the rate of symptom progression in patients who already have Alzheimer’s dementia.”

The study comes two years after UTHealth Houston researchers found a possible link between the flu vaccine and reduced risk of Alzheimer’s disease. This new study analysed a much larger sample than previous research, including 935 887 flu-vaccinated patients and 935 887 non-vaccinated patients.

During four-year follow-up appointments, about 5.1% of flu-vaccinated patients were found to have developed Alzheimer’s disease. Meanwhile, 8.5% of non-vaccinated patients had developed Alzheimer’s disease during follow-up.

These results underscore the strong protective effect of the flu vaccine against Alzheimer’s disease, according to Bukhbinder and Schulz. However, the underlying mechanisms behind this process require further study.

“Since there is evidence that several vaccines may protect from Alzheimer’s disease, we are thinking that it isn’t a specific effect of the flu vaccine,” said Professor Paul. E. Schulz, MD, senior author of the study. “Instead, we believe that the immune system is complex, and some alterations, such as pneumonia, may activate it in a way that makes Alzheimer’s disease worse. But other things that activate the immune system may do so in a different way – one that protects from Alzheimer’s disease. Clearly, we have more to learn about how the immune system worsens or improves outcomes in this disease.”

Past research has uncovered a decreased risk of dementia associated with prior exposure to various adulthood vaccinations, including those for tetanus, polio, and herpes, in addition to the flu vaccine and others.

Additionally, as more time passes since the introduction of the COVID vaccine and longer follow-up data becomes available, Dr Bukhbinder said it seeing if there is a similar link between COVID vaccination and the risk of Alzheimer’s disease.

Source: The University of Texas Health Science Center at Houston

Categories : AgeingTags :

In Women, an Optimistic Outlook Leads to Longer Lifespan

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Photo by Loren Joseph on Unsplash

In a study published in the Journal of the American Geriatrics Society with 159 255 female participants from a variety of racial and ethnic backgrounds, higher levels of optimism were associated with longer lifespans and a greater likelihood of living past 90 years of age. 

Investigators found that the link between optimism and longevity was evident across racial and ethnic groups, and that lifestyle factors accounted for nearly one-quarter of the optimism-lifespan association. 

“Although optimism itself may be patterned by social structural factors, our findings suggest that the benefits of optimism for longevity may hold across racial and ethnic groups,” said lead author Hayami K. Koga, of the Harvard T.H. Chan School of Public Health. “Optimism may be an important target of intervention for longevity across diverse groups.”  

Source: Wiley

Categories : Ageing CancerTags :

Supplementation Effective in Slowing Age-related Macular Degeneration

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Credit: National Eye Institute

A pair of major studies established that dietary supplements can slow progression of age-related macular degeneration (AMD). In a new report published in JAMA Ophthalmology, scientists went through 10 years of Age-Related Eye Disease Studies (AREDS2) data and showed that the AREDS2 formula, which substituted antioxidants lutein and zeaxanthin for beta-carotene, not only reduces risk of lung cancer due to beta-carotene, but is also more effective at reducing risk of AMD progression, compared to the original formula.

“Because beta-carotene increased the risk of lung cancer for current smokers in two NIH-supported studies, our goal with AREDS2 was to create an equally effective supplement formula that could be used by anyone, whether or not they smoke,” said Emily Chew, MD, lead author of the study report. “This 10-year data confirms that not only is the new formula safer, it’s actually better at slowing AMD progression.”

AMD is a degenerative disease of the retina, the light-sensitive tissue at the back of the eye. Progressive death of retinal cells in the macula, the part of the retina that provides clear central vision, eventually leads to blindness. Treatment can slow or reverse vision loss; however, no cure for AMD exists.

The original AREDS study, launched in 1996, showed that a dietary supplement formulation (50 mg vitamin C, 400 international units vitamin E, 2mg copper, 80mg zinc, and 15mg beta-carotene) could significantly slow the progression of AMD from moderate to late disease. However, two concurrent studies also revealed that people who smoked and took beta-carotene had a significantly higher risk of lung cancer than expected.

In AREDS2, begun in 2006, Dr Chew and colleagues compared the beta-carotene formulation to one with 10 mg lutein and 2 mg zeaxanthin instead. Like beta-carotene, lutein and zeaxanthin are antioxidants with activity in the retina. The beta-carotene-containing formation was only given to participants who had never smoked or who had quit smoking.

At the end of the five-year AREDS2 study period, the researchers concluded that lutein and zeaxanthin did not increase risk for lung cancer, and that the new formation could reduce the risk of AMD progression by about 26%. After the completion of the five-year study period, the study participants were all offered the final AREDS2 formation that included lutein and zeaxanthin instead of beta-carotene.

In this new report, the researchers followed up with 3883 of the original 4203 AREDS2 participants an extra five years from when the AREDS2 study ended in 2011, collecting information AMD progression, and lung cancer diagnosis. Even though all the participants had switched to the formula containing lutein and zeaxanthin after the end of the study period, the follow up study continued to show that beta-carotene increased risk of lung cancer for people who had ever smoked by nearly double. No increased risk for lung cancer was seen in those receiving lutein/zeaxanthin. In addition, after 10 years, the group originally assigned to receive lutein/zeaxanthin had an additional 20% reduced risk of progression to late AMD compared to those originally assigned to receive beta-carotene.

“These results confirmed that switching our formula from beta-carotene to lutein and zeaxanthin was the right choice,” said Dr Chew.

Source: NIH/National Eye Institute

Categories : Ageing Surgeries & ProceduresTags :

Progressive Exercise Programme Improves Outcomes after Hip Surgery

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Carers help an old man to walk
Photo by Kampus Productions on Pexels

A study published in the Journal of the American Geriatrics Society shows that a 12-month home-based supervised exercise programme can help to improve physical performance and functioning after patients undergo hip fracture surgery.

Hip fracture is a major health problem among older people, often resulting in long-term, sometimes persistent, functional impairments such as poor mobility and reduced independence in daily activities. Sedentary behaviour and low level of physical activity are also common among patients recovering from surgical repair of a hip fracture.

Standard care post-discharge care does not seem to meet the requirements of effective rehabilitation, as many patients with hip fractures do not reach their pre-fracture level of functioning. Growing evidence shows that multidisciplinary and well-coordinated rehabilitation started at the hospital and continued after discharge enhances the recovery of patients with hip fractures. Multicomponent rehabilitation in particular, which includes individualised and progressive resistance training, has improved functioning and mobility and decreased dependency in everyday activities. Longer lasting exercise programs of 6 to 12 months duration have reduced or reversed incident disability after hip fractures.

For the study, 121 patients aged 60 years and older were randomised to either an exercise group or a usual care group as a control. Home-based exercise sessions were delivered by physiotherapists twice a week and included strength, balance, mobility, and functional components as well as brief counselling on physical activity and nutrition.

Compared with patients in the usual care group, patients in the exercise group saw more improvements over the course of a year in their physical performance, their handgrip strength, and their ability to complete certain activities of daily living.

“It is worthwhile to invest in rehabilitation exercise for older people after hip fracture. Better functioning benefits the individual and also society,” said lead author Paula K. Soukkio, MSc, of the South Karelia Social and Health Care District (Eksote), in Finland.

Source: Wiley

Categories : Ageing Diseases, Syndromes and ConditionsTags :

Early Warning Signs for Age-related Macular Degeneration

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Credit: National Eye Institute

In an important step in treating a major cause of blindness, scientists have successfully identified early signs of age-related macular degeneration (AMD), in which higher number of mast cells are observed. This finding could be exploited by new treatments before symptoms develop. The study is published in PNAS.

Scientists have long known that people with certain genes on chromosomes 1 and 10 have a 2- to 3-fold higher risk of developing AMD, although lifestyle factors also play a role.

The team identified higher numbers of mast cells in the eyes of people when either of the risk genes were present, even when there were symptoms, suggesting an early mechanism in common.

They also showed the mast cells release enzymes in the back of the eye which then damage structures underneath the retina that in time is likely to damage the retina itself.

Mast cells exist in most tissues and are one of the immune system’s first defenses against infection, especially parasitic disease and damage.

Scientists already know there are more mast cells in the choroid in people with established AMD. The current study, however, identified higher levels in people before the disease develops.

The genes on chromosome 1 are linked to a part of the immune system called the complement cascade, which is associated with a risk of AMD.

Though the functional role of genes expressed by chromosome 10 are not known, but increased risk of AMD is.

Dr Richard Unwin, one of the study leaders, said: “What is really exciting about this work is that we are studying tissue from people before they have signs of the disease. This gives us a look into the very earliest stages, and gives us hope that we can intervene to stop the disease developing and ultimately prevent loss of vision”

The scientists used healthy human eye tissue donated post mortem to the Manchester Eye Tissue Repository.

They identified those who are at risk of developing age-related macular degeneration based on their risk genes, and discovered underlying changes in the tissue of the otherwise healthy at-risk individuals.

They collected retinal tissue from the back of donor eyes post mortem, following removal of the cornea for transplantation.

Then they took a small sample from the macula and removed the cells to leave a thin layer of membrane which supports the photoreceptors called rod and cone cells and is where disease begins.

They analysed the proteins present in the membrane from 30 people using mass spectrometry, which identifies protein components based on their mass, to find differences in the tissue make-up between those with and without genetic risk of AMD.

The mass spectrometry, identified a series of enzymes which are made almost exclusively by mast cells. In tissue from an additional 53 people, higher levels of mast cells were found in patients with higher disease risk.

Dr Unwin added: “We next need to look at how mast cells are activated, and whether by preventing, or clearing mast cell activation we can slow or stop disease development. There are several researchers and companies looking at complement mediated-therapies for AMD and while these are promising for Chr1-related disease there is no evidence that they will have an effect on Chr10 disease. A therapy designed to target mast cell activation as a unified mechanism could in theory treat all patients with AMD and prevent sight loss.”

Source: University of Manchester

Categories : AgeingTags :

CSF From Young Mice Improves Memory of Older Mice

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Mouse
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In a finding reminiscent of how vampires and zombies in fiction get sustenance from their victims, a team of researchers reported in the journal Nature that injecting cerebrospinal fluid (CSF) from young mice into old mice improves the memory and cognitive abilities of the older mice

Such an approach is nothing new, although the chief obstacle was safely harvesting such a tiny amount of CSF from the small animals. About two decades ago, studies had reported that transferring blood from younger mice to older ones notably improved the health of the older mice, giving them a ‘rejuvenating’ effect. It did not take long for people to take note of this discovery, with a startup company offering transfers of young people’s plasma for exorbitant amounts to wealthy older clients in the unproven hopes of reversing ageing. Fears of a dystopian future were averted when the US Food and Drug Administration released a statement stating such transfers had no clinical benefit, and the company folded. However, research continued.

Since ageing is too complex to measure in a clinical trial anyway, scientists have been focusing on tackling specific aspects of it, such as in neurodegenerative diseases like Alzheimer’s and research has continued in this direction. A few years ago, human umbilical cord plasma was shown to revitalise hippocampal function in aged mice, and previous work led by Tony Wryss-Coray, PhD had found that young mouse blood improved age-related impairments in cognition. Studies of fear conditioning had shown that proliferation of oligodendrocyte precursor cells (OPCs) was necessary for fear formation, which raised the question of whether CSF might affect this.

Infusing CSF taken from 10 week old mice over seven days, researchers trained 18 month old mice to associate a flashing light with an electric shock to the foot. The CSF infusion was shown to improve recall of the fear stimulus in the older mice and induce greater OPC proliferation.

“The broad message here is that the aging process is malleable, which of course is not new because of this paper,” senior author Dr Wyss-Coray said in an interview with MedPage Today. “But it adds to the idea that aging is a potential therapeutic target, a process we can start to understand better and start to manipulate.”

“The other message – one that’s more brain-specific – is that if you improve the environment in which neurons live, you can actually have a substantial improvement in function,” he added. “That may be as important, or even more important sometimes, than targeting neuronal processes themselves.”

The researchers isolated fibroblast growth factor 17 (Fgf17) infusion as being necessary for OPC proliferation, and blocking it in young mice impaired cognition.

“This suggests that Fgf17 is not only able to recapitulate some of the useful effects of CSF from young mice, but it also seems to be necessary to make a young brain function at its full capacity,” Dr Wyss-Coray said.

Categories : AgeingTags :

Genetic Risk Score for Hip or Knee Replacements

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A Monash University-led research team has developed a risk score based on individuals’ genetic data to predict their likelihood of needing hip or knee replacement surgery for osteoarthritis. The team validated the score’s predictive ability in a study published in Arthritis & Rheumatology.  

The score incorporates 10 genetic sequence variants for predicting a person’s risk of needing knee replacement surgery and 37 genetic sequence variants for predicting the risk of needing hip replacement surgery.  

Among 12093 individuals of European genetic descent aged 70 years or older, 1422 (11.8%) had knee replacements and 1,297 (10.7%) had hip replacements. Participants with high risk scores had a 1.44-times higher odds of knee replacement and a 1.88-times higher odds of hip replacement, compared with those with low risk scores.   

 “Genetic scores, such as the one we developed, do not change over a person’s life. They provide an individual  with further information about their risk of severe osteoarthritis in later life and have the potential to improve prevention of severe knee and hip osteoarthritis by identifying those who may benefit from early intervention,” said senior author Flavia Cicuttini, PhD, of Monash University.  

Source: Wiley