Tag: ageing

Categories : AgeingTags :

Friendly ‘Zombie’ Cells Help Promote Tissue Repair

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Photo by julien Tromeur on Unsplash

While most senescent cells may be harmful “zombies” spewing toxic compounds and should be targeted to reduce the risk of age-related disease, not all of them are like this. In fact, according to new research in Science, some of them embedded in young, healthy tissues seem to help repair damage.

Scientists have now seen these cells in action in lung tissue, as well as other organs that serve as barriers in the body, such as the small intestine, colon and skin. When they used drugs called senolytics to kill these cells, injuries to lung tissues healed more slowly.

“Senescent cells can occupy niches with privileged positions as ‘sentinels’ that monitor tissue for injury and respond by stimulating nearby stem cells to grow and initiate repair,” said Tien Peng, MD, associate professor of pulmonary, critical care, allergy and sleep medicine, and senior author of the study.

Ageing cells can both damage and heal

A/Prof Peng said it was understandable that scientists at first viewed senescent cells as purely detrimental. As people age, senescent cells – often termed “zombie cells” – accumulate that have characteristics of old, worn-out cells, including the inability to make new cells. Instead of dying like normal aged cells, they to live on, spewing a cocktail of inflammatory compounds that form the senescence associated secretory phenotype (SASP). These factors are linked to Alzheimer’s disease, arthritis, and other age-related maladies including cancer.

Using senolytics that selectively kill “zombie cells,” researchers made the exciting discovery that clearing senescent cells from animals thwarted or diminished age-related disease and extended the lifespan of the animals. Thereafter, a boom of activity ensued in research labs and pharmaceutical companies focused on discovering and refining more powerful versions of these drugs.

But killing off senescent cells has dangers, A/Prof Peng said. For one thing, this current study showed that senescent cells also possess the ability to promote normal healing through activation of stem cell repair. “Our study suggests that senolytics could adversely affect normal repair, but they also have the potential to target diseases where senescent cells drive pathologic stem cell behaviour,” said A/Prof Peng.

Lighting up senescent cells

One major challenge to studying senescent cells is that biomarkers of senescence (such as the gene p16) are often quite sparse, making it difficult to detect the cells. In early experiments, researchers extracted cells called fibroblasts into culture dishes, allowing them to grow and produce enough cells to experiment with, and then stressed the cells with chemicals that induced them to become senescent. But in living organisms, cells interact with tissues around them, strongly affecting the cells’ gene activity. This means that the characteristics of cells growing isolated in a glass dish could be quite different from that of cells in their natural environment.

To create a more powerful tool for their studies, the researchers improved on a common technique of fusing a relevant gene – in this case, the p16 gene, which is overly active in senescent cells –with green fluorescent protein (GFP) as a marker that can reveal the location of the cells under ultraviolet light. By enhancing the quantity and stability of green fluorescent protein in these senescent cells, the fluorescent signal was greatly amplified, finally enabling the researchers to see senescent cells in their natural habitat of living tissues.

“Zombies” stimulate stem cells shortly after birth

Using this highly sensitive tool, the researchers found that senescent cells exist in young and healthy tissues to a greater extent than previously thought, and actually begin appearing shortly after birth. The scientists also identified specific growth factors that senescent cells secrete to stimulate stem cells to grow and repair tissues. Relevant to aging and tissue injury is the discovery that cells of the immune system such as macrophages and monocytes can activate senescent cells, suggesting that inflammation seen in aged or damaged tissue is a critical modifier of senescent cell activity and regeneration.

In their studies of lung tissue, A/Prof Peng’s team observed green glowing senescent cells lying next to stem cells on the basement membrane that serves as a barrier preventing foreign cells and harmful chemicals from entering the body and also allows oxygen to diffuse from air in the lungs into underlying tissues. Damage can occur at this dynamic interface. The team saw senescent cells in similar positions in other barrier organs such as small intestine, colon, and skin, and their experiments confirmed that if senescent cells were killed with senolytics, lung stem cells were not able to properly repair the barrier surface.

Source: EurekAlert!

Categories : Ageing GeneticsTags :

When it Comes to Longevity, Physical Activity Beats Genes

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Although low physical activity and greater time spent sitting are well known to be linked to a higher risk of death, a study published in Journal of Aging and Physical Activity showed that a genetic predisposition to longevity was not a substitute for sitting less and greater physical activity, which can benefit even those not gifted with such genes.

“The goal of this research was to understand whether associations between physical activity and sedentary time with death varied based on different levels of genetic predisposition for longevity,” said doctoral student Alexander Posis, lead author of the study.

In 2012, as part of the Women’s Health Initiative Objective Physical Activity and Cardiovascular Health study (OPACH), researchers began measuring the physical activity of 5446 women aged 63 and older, following them through 2020 to determine mortality. Participants wore a research-grade accelerometer for up to seven days to measure how much time they spent moving, the intensity of physical activity, and sedentary time.

Higher levels of light physical activity and moderate-to-vigorous physical activity were found to be associated with lower risk of death. Higher sedentary time was associated with higher risk of mortality. These associations were consistent among women who had different levels of genetic predisposition for longevity.

“Our study showed that, even if you aren’t likely to live long based on your genes, you can still extend your lifespan by engaging in positive lifestyle behaviours such as regular exercise and sitting less,” said Assistant Professor Aladdin H. Shadyab, PhD, senior author. “Conversely, even if your genes predispose you to a long life, remaining physically active is still important to achieve longevity.”

Given the ageing adult population in the United States, and longer time spent engaging in lower intensity activities, the study findings support recommendations that older women should participate in physical activity of any intensity to reduce the risk of disease and premature death, wrote the authors.

Source: University of California – San Diego

Categories : Ageing General InterestTags :

The 100 Year Old Doctor Who Won’t Hang Up His Stethoscope

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Credit: “What’s Next” Documentary

At 100, Dr Howard Tucker holds the Guinness world record for being the world’s oldest practising doctor. Though he has only just stopped seeing patients, he still teaches medical residents at St. Vincent Charity Medical Center in Ohio, USA.

Having practised medicine for 75 years, the secret is to keep going, he said. “I look upon retirement as the enemy of longevity,” Dr Tucker told TODAY over a video call. He has a computer and smartphone, and is determined to keep up with technology.

“I think that to retire, one can face potential shrivelling up and ending in a nursing home. It’s fun staying alive and working…  It’s delightful work. Every day I learn something new.”

Born on July 10, 1922 and graduating from medical school in 1947, Dr Tucker got the “gift of COVID” from one of his relatives at his 100th birthday last month, but recovered quickly and felt fine. He even broke is neck while skiing in the late 1980s, though he “came out of it totally intact”.

At age 67 he passed the Ohio Bar Exam because he was interested in law.

Tucker shared some of his longevity advice with TODAY:

“Heredity and family history of longevity is a healthy start. However, it must be supported by moderation of nutrition, alcohol, and happiness,” Dr Tucker explained in his Guinness World Records entry.

Longevity runs in his family: his mother lived to 84 and his father to 96, and he has avoided the diseases of ageing such as heart disease and dementia. In addition, Dr Tucker never smokes but drinks alcohol occasionally, and eats in moderation. He has exercised his entire life – though he is now banned from skiing. The day after his 100th birthday, he threw the opening pitch for a baseball game.

His advice is to not retire , and stay active. Though there are jobs which people can’t or don’t wat to do anymore as they age, people should at least take up a hobby or do communal work to provide a daily stimulus for the brain.

The other challenge is to keep learning. As well as earning his law degree, he stayed current with technology, for which he credits his grandson, Austin, who is also making a documentary about the centenarian’s life. He also keeps up with his field of neurology, which he follows with excitement.

Finally, Dr Tucker said that you have to cultivate happiness. “You have to be happy in your job and in your domestic life,” he said.

Source: Today

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 : AgeingTags :

In Women, an Optimistic Outlook Leads to Longer Lifespan

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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
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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 Skeletal SystemTags :

Osteoporosis in Men is Often Overlooked

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Osteoporosis in men is often overlooked by health care professionals, found the authors of a review published in The Lancet Diabetes and Endocrinology. There is a desperate need for raising awareness of the condition in men to help improve outcomes for patients, the authors said.

Women are generally at higher risk of developing osteoporosis, as their bone density declines more rapidly than men at an earlier age, especially post-menopause. In most populations, men have larger and stronger bone and joint surfaces, so they can be overlooked when diagnosing the condition.

Reviewing available data on the condition in men, researchers found that they are generally diagnosed later, comply with treatment less and present to hospital in older ages than women. With fatality rates from hospitalisations with fragility fractures, like a broken hip, being higher than women.

The review’s author, Dr Tatiane Vilaca, said: “Generally diagnosis of osteoporosis happens when a patient presents at hospital with some kind of fragility fracture in older age, for example falling from standing height, and breaking a hip, wrist or spine.

“Research suggests men hospitalised with hip fractures tend to be older than women, which could be because the condition develops more slowly in men. As older people are usually slightly frailer, with poorer states of overall health, this could explain the slightly higher levels of disability and mortality associated in men with osteoporosis who are hospitalised following a fracture.”

The review found that although there is a lack of research about which treatment options are most effective in men, diagnosis and treatment options are effective.

The team believe further research specifically tailored to osteoporosis in male patients will help improve current diagnosis systems, helping clinicians with earlier diagnosis, and a focus on education for patients will support compliance with drug treatment programs, all improving outcomes for men living with osteoporosis.

Dr. Richard Eastell, Professor of Bone Metabolism at the Department of Oncology and Metabolism, said: “As women make up larger numbers of people living with osteoporosis, the data we have on the progression of the condition in men is currently not as robust. This updated review shows that further studies of male patients could help improve current diagnosis systems, as well as resources for the education of primary care clinicians and the general public on the early warning signs of osteoporosis in men.”

Dr. Vilaca added: “Despite the current gap in knowledge, men can still easily be screened for osteoporosis at their general practitioner surgery.

“Anyone with a family history of osteoporosis, broken bones, or fractures, those with acute back pain or a loss of height should be encouraged to have a check-up.

“These are all early warning signs of the condition in both men and women, and early preventative treatment is the best way to ensure a slower disease progression and longer, healthier life without a fracture.”

Source: University of Sheffield

Categories : AgeingTags :

Seven Hours’ Sleep is Optimal in Middle Age and Older

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Sleeping woman
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According to research published in Nature Aging, seven hours is the ideal amount of sleep for people in their middle age and upwards, with too little or too much little sleep associated with poorer cognitive performance and mental health.

Sleep plays an important role in enabling cognitive function and maintaining good psychological health, and also removes waste products from the brain. Alterations in sleep patterns appear during ageing, including difficulty falling asleep and staying asleep, and decreased quantity and quality of sleep. It is thought that these sleep disturbances may contribute to cognitive decline and psychiatric disorders in the ageing population.

Scientists from the UK and China examined data from nearly 500 000 adults aged 38–73 years from the UK Biobank. Participants were asked about their sleeping patterns, mental health and wellbeing, and took part in a series of cognitive tests. Brain imaging and genetic data were available for almost 40 000 of the study participants.

The researchers found in their analysis that both insufficient and excessive sleep duration were associated with impaired cognitive performance, such as processing speed, visual attention, memory and problem-solving skills. The optimal amount of sleep was found to be seven hours per night for cognitive performance and good mental health. More symptoms of anxiety and depression and worse overall wellbeing were associated with sleeping for longer or shorter durations.

The researchers say one possible reason for the association between insufficient sleep and cognitive decline may be due to the disruption of slow-wave — ‘deep’ — sleep. Disruption to this type of sleep has been shown to have a close link with memory consolidation as well as the build-up of amyloid — a key protein which, when it misfolds, can cause ‘tangles’ in the brain characteristic of some forms of dementia. Additionally, lack of sleep may hamper the brain’s ability to rid itself of toxins.

The amount of sleep was also linked differences in the structure of brain regions involved in cognitive processing and memory, again with greater changes associated with greater than or less than seven hours of sleep.

Consistently getting seven hours’ sleep each night was also important to cognitive performance and good mental health and wellbeing. Interrupted sleep patterns have previously been shown to be associated with increased inflammation, indicating a susceptibility to age-related diseases in older people.

Professor Jianfeng Feng from Fudan University in China said: “While we can’t say conclusively that too little or too much sleep causes cognitive problems, our analysis looking at individuals over a longer period of time appears to support this idea. But the reasons why older people have poorer sleep appear to be complex, influenced by a combination of our genetic makeup and the structure of our brains.”

The researchers say the findings suggest that insufficient or excessive sleep duration may be a risk factor for cognitive decline in ageing. This is supported by previous studies that have reported a link between sleep duration and the risk of developing Alzheimer’s disease and dementia, in which cognitive decline is a hallmark symptom.

Professor Barbara Sahakian from the Department of Psychiatry at the University of Cambridge, one of the study’s authors, said: “Getting a good night’s sleep is important at all stages of life, but particularly as we age. Finding ways to improve sleep for older people could be crucial to helping them maintain good mental health and wellbeing and avoiding cognitive decline, particularly for patients with psychiatric disorders and dementias.”

Source: University of Cambridge

Categories : AgeingTags :

Online Tool Helps Older Adults Decide When to Stop Driving

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Older woman smiling
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A recent randomised controlled trial published in the Journal of the American Geriatrics Society found that an online decision aid may help older adults decide whether and when to stop driving.

Compared with older adults who viewed an educational website, those who viewed the decision aid, called Healthwise® DDA, had lower decisional conflict and higher knowledge about whether to stop or continue driving. The online aid has six sections: “Get the Facts,” “Compare Options,” “Your Feelings,” “Your Decision,” “Quiz Yourself,” and “Your Summary.”

In the National Institute on Aging–funded trial of 301 participants aged 70 years and older, 51.2% of whom identified as female,. the tool had high acceptability, with nearly all of those who used it saying that they would recommend it to others.

“The decision about when to stop driving is a difficult and emotional one – and also one most older adults eventually face,” explained lead author Marian Betz, MD, MPH, of the University of Colorado and the Rocky Mountain Regional VA Medical Center. “Tools like this one may help older adults make the decision and, hopefully, reduce negative feelings about the process.”

Source: Wiley