Tag: ageing

Categories : Ageing Metabolic DisordersTags :

Mouse Study Highlights Potential Therapeutic for Metabolic Syndrome

On By ModernMedia
Photo by Diana Polekhina on Unsplash

Mopping up free radicals with antioxidants was a major health fad in the 1970s. In an effort to supposedly blunt the effects of aging and stave off chronic disease, people took huge amounts of antioxidants in the form of minerals and vitamins. Not only was this ineffective, it sometimes caused harm because untargeted antioxidants also compromised beneficial cellular signalling pathways. As theories of mitochondrial causes of disease fell out of favour, this health fad disappeared along with bell bottoms and disco.

Now, research recently published in Free Radical Biology and Medicine suggests a new way of dealing with free radicals: rather than mop them up, take a pill that selectively keeps them from being produced in the first place. Building on this work, collaborative research between the Buck and Calico Labs shows that specifically inhibiting free radical production at a particular mitochondrial site prevents and treats metabolic syndrome in mice, by preventing and reversing insulin resistance.

“We think that mitochondrial radical production drives many chronic diseases of aging, and that blocking the production of free radicals is a viable disease-treating and anti-aging intervention,” said Martin Brand, PhD, Buck Professor Emeritus and senior investigator of the study. “We’ve found a way to selectively keep problematic free radicals in check without compromising normal energy production in the mitochondria. These compounds act like a cork in a wine bottle. They plug a specific site so that it doesn’t produce free radicals, without hindering the mitochondria’s critical function of energy metabolism. We look forward to continuing this groundbreaking area of research.”

The orally bioavailable compound that has been developed, S1QEL1.719 (a new “S1QEL” – Suppressor of site IQ Electron Leak), was given both prophylactically and therapeutically to mice fed a high-fat diet that causes metabolic syndrome. Treatment decreased fat accumulation, strongly protected against decreased glucose tolerance and prevented or reversed the increase in fasting insulin levels by protecting against the development of insulin resistance.

Acting on mitochondrial complex I highlights potential interventions for other conditions

S1QEL1s act on site IQin mitochondrial complex I. (The mitochondrial electron transport chain consists of four protein complexes integrated into the inner mitochondrial membrane. Together they carry out a multi-step process, oxidative phosphorylation, through which cells derive 90% of their energy.)

First author and Buck staff scientist Mark Watson, Ph.D., says current literature strongly implicates complex I in a number of different diseases, from metabolic syndrome to Alzheimer’s, fatty liver disease, and noise-induced hearing loss, as well as the underlying aging process itself.

“S1QELs don’t sequester oxidants or radicals. Rather, they specifically inhibit radical production at the IQ site on complex I without interfering with other sites,” Watson said. “So the normal redox signaling that we require in our cells will continue. S1QELs just modulate that one site. They are very clean, very specific, and do not disrupt mitochondrial functioning like inhibitors of mitochondria do.”

Brand says the data shows that free radical production from complex I is an essential driver of insulin resistance and metabolic syndrome, a major disease of poor lifestyle choices and of aging. He says this feature is a strong reason to revisit the mitochondrial theory of aging. “These compounds fine-tune mitochondrial production of free radicals,” he said. “And it’s really interesting; just inhibiting this specific site improves the whole redox environment and prevents metabolic disease, and that is amazing.”

Source: Buck Institute for Research on Aging

Categories : Cardiovascular Disease Diet and NutritionTags :

Five Years of High-dose Vitamin D Reduced Atrial Fibrillation Risk

On By ModernMedia
Photo by Michele Blackwell on Unsplash

Taking higher-than-recommended doses of vitamin D for five years reduced the risk of atrial fibrillation in older adults, according to a randomised controlled study conducted in Finland and published in the American Heart Journal.

Atrial fibrillation is the most common arrhythmia, the risk of which increases with age, and which is associated with an increased risk of stroke, heart failure and mortality. Vitamin D has been shown to have an effect, for example, on the atrial structure and the electrical function of the heart, suggesting that vitamin D might prevent atrial fibrillation.

Conducted at the University of Eastern Finland in 2012–2018, the main objective of the Finnish Vitamin D Trial (FIND) was to explore the associations of vitamin D supplementation with the incidence of cardiovascular diseases and cancers. The five-year study involved 2 495 participants, men aged 60 and older, and women aged 65 and older, who were randomised into three groups: one placebo group and two vitamin D3 supplementation groups, with one of the groups taking a supplement of 40µg (1600 IU) per day, and the other a supplement of 80µg (3200 IU) per day. All participants were also allowed to take their personal vitamin D supplement, up to 20µg (800 IU) per day, which at the beginning of the study was the recommended dose for this age group. Participants had no diagnoses of cardiovascular disease or cancer at baseline, and they completed comprehensive health-related questionnaires, both at the beginning. Data on the occurrence of diseases and deaths were also obtained from Finnish nationwide health registers. Approximately 20% of participants were randomly selected for more detailed examinations and blood samples.

During the five-year study, 190 participants were diagnosed with atrial fibrillation: 76 in the placebo group, 59 in the 40µg group, and 55 in the 80 micrograms group. The risk of atrial fibrillation was 27% lower in the 40µg group, and 32% lower in the 80 micrograms group, when compared to the placebo group. In the sub-cohort selected for more detailed examinations, the mean baseline serum calcidiol concentration, which is a marker of the body’s vitamin D concentration, was relatively high, 75nmol/l. After one year, the mean calcidiol concentration was 100nmol/L in the 40µg group, and 120nmol/l in the 80µg group. No significant change in the calcidiol concentration was observed in the placebo group.

Only two randomised trials tried to test whether vitamin D supplementation reduces AF risk in healthy adults, and they did not observe an effect when using doses of 10µg (400 IU) or 50µg (2000 IU) per day. Further confirmation of the present results from the FIND study is therefore needed before doses of vitamin D that significantly exceed current recommendations can be recommended for preventing atrial fibrillation. The FIND study has previously published findings showing no association with the incidence of other cardiovascular events or cancers.

Source: University of Eastern Finland

Categories : Ageing Diet and NutritionTags :

Taurine may Help Extend Healthy Lifespan

On By ModernMedia
Photo by Barbara Olsen on Pexels

A deficiency of the amino acid taurine is a driver of ageing in animals, according to a new study published in Science. The same study also found that taurine supplements can slow down the ageing process in worms, mice, and monkeys and can even extend the healthy lifespans of middle-aged mice by up to 12%.

“For the last 25 years, scientists have been trying to find factors that not only let us live longer, but also increase healthspan, the time we remain healthy in our old age,” says study leader Vijay Yadav, PhD, assistant professor of genetics & development at Columbia University. “This study suggests that taurine could be an elixir of life within us that helps us live longer and healthier lives.”

Anti-ageing molecules within us

Many studies into ageing have found that various molecules carried through the bloodstream are associated with ageing. Less certain is whether these molecules actively direct the ageing process or are just passengers going along for the ride. If a molecule is a driver of ageing, then restoring its youthful levels would delay ageing and increase healthspan, the years we spend in good health.

Taurine first came into Yadav’s view during his previous research into osteoporosis that uncovered taurine’s role in building bone. Around the same time, other researchers were finding that taurine levels correlated with immune function, obesity, and nervous system functions.

“We realised that if taurine is regulating all these processes that decline with age, maybe taurine levels in the bloodstream affect overall health and lifespan,” Yadav says.

Taurine declines with age, supplementation increases lifespan in mice

First, Yadav’s team looked at levels of taurine in the bloodstream of mice, monkeys, and people and found that the taurine abundance decreases substantially with age. In people, taurine levels in 60-year-old individuals were only about one-third of those found in 5-year-olds.

“That’s when we started to ask if taurine deficiency is a driver of the ageing process, and we set up a large experiment with mice,” Yadav says.

The researchers started with close to 250 14-month-old female and male mice (about 45 years old in people terms). Every day, the researcher fed half of them a bolus of taurine or a control solution. At the end of the experiment, Yadav and his team found that taurine increased average lifespan by 12% in female mice and 10% in males. For the mice, that meant three to four extra months, equivalent to about seven or eight human years.

Taurine supplements in middle age improves health in old age

To learn how taurine impacted health, Yadav brought in other ageing researchers who investigated the effect of taurine supplementation on the health and lifespan in several species.

These experts measured various health parameters in mice and found that at age 2 (60 in human years), animals supplemented with taurine for one year were healthier in almost every way than their untreated counterparts.

The researchers found that taurine suppressed age-associated weight gain in female mice (even in “menopausal” mice), increased energy expenditure, increased bone mass, improved muscle endurance and strength, reduced depression-like and anxious behaviours, reduced insulin resistance, and promoted a younger-looking immune system, among other benefits.

“Not only did we find that the animals lived longer, we also found that they’re living healthier lives,” Yadav says.

At a cellular level, taurine improved many functions that usually decline with age: The supplement decreased the number of “zombie cells” (old cells that should die but instead linger and release harmful substances), increased survival after telomerase deficiency, increased the number of stem cells present in some tissues (which can help tissues heal after injury), improved the performance of mitochondria, reduced DNA damage, and improved the cells’ ability to sense nutrients.

Similar health effects of taurine supplements were seen in middle-aged rhesus monkeys, which were given daily taurine supplements for six months. Taurine prevented weight gain, reduced fasting blood glucose and markers of liver damage, increased bone density in the spine and legs, and improved the health of their immune systems.

Randomised clinical trial needed

The researchers do not know yet if taurine supplements will improve health or increase longevity in humans, but two experiments they conducted suggest taurine has potential.

In the first, Yadav and his team looked at the relationship between taurine levels and approximately 50 health parameters in 12 000 European adults aged 60 and over. Overall, people with higher taurine levels were healthier, with fewer cases of type 2 diabetes, lower obesity levels, reduced hypertension, and lower levels of inflammation. “These are associations, which do not establish causation,” Yadav says, “but the results are consistent with the possibility that taurine deficiency contributes to human ageing.”

The second study tested if taurine levels would respond to an intervention known to improve health: exercise. The researchers measured taurine levels before and after a variety of male athletes and sedentary individuals finished a strenuous cycling workout and found a significant increase in taurine among all groups of athletes (sprinters, endurance runners, and natural bodybuilders) and sedentary individuals.

“No matter the individual, all had increased taurine levels after exercise, which suggests that some of the health benefits of exercise may come from an increase in taurine,” Yadav says.

Only a randomized clinical trial in people will determine if taurine truly has health benefits, Yadav adds. Taurine trials are currently underway for obesity, but none are designed to measure a wide range of health parameters.

Other potential anti-ageing drugs – including metformin, rapamycin, and NAD analogues – are being considered for testing in clinical trials.

“I think taurine should also be considered,” Yadav says. “And it has some advantages: Taurine is naturally produced in our bodies, it can be obtained naturally in the diet, it has no known toxic effects (although it’s rarely used in concentrations used ), and it can be boosted by exercise.

“Taurine abundance goes down with age, so restoring taurine to a youthful level in old age may be a promising anti-ageing strategy.”

Source: Columbia University Irving Medical Center

Categories : Ageing Diet and NutritionTags :

Can Low-carbohydrate or Low-fat Diets Extend Lifespan?

On By ModernMedia

Better diets are needed to address the macronutritional needs of an ageing population. Short-term clinical trials have demonstrated the health benefits of low-carbohydrate diets (LCDs) and low-fat diets (LFDs) for weight loss and heart protection. Now a study published in the Journal of Internal Medicine looks at the effects of these diets on mortality in middle-aged and older adults.

In the study of 371 159 individuals aged 50 to 71 years, 165 698 deaths occurred over a median follow-up of 23.5 years.

A healthy LFD – characterised by low intake of saturated fat and high intakes of plant protein and high-quality carbohydrates – was related to fewer deaths from all causes, from cardiovascular diseases, and from cancers. In contrast, an overall LCD and an unhealthy LCD were associated with significantly higher total, cardiovascular, and cancer mortality rates. A healthy LCD was associated with slightly lower death rates.

“Our results support the importance of maintaining a healthy LFD with less saturated fat in preventing all-cause and cause-specific mortality among middle-aged and older people,” the authors wrote.

Source: Wiley

Categories : Ageing Pain ManagementTags :

The Impacts of Persistent Pain in Older Adults

On By ModernMedia
Woman holding an old man's hand
Photo by Matthias Zomer on Pexels

In a study of 5589 US adults aged 65 years and older, persistent pain was common and was linked to meaningful declines in physical function and well-being over 7 years. Reporting in the Journal of the American Geriatrics Society, investigators found that 38.7% of participants reported persistent pain, and 27.8% reported intermittent pain. (“Persistent pain” was defined as being bothered by pain in the last month in two consecutive annual interviews and “intermittent” pain was defined as bothersome pain in one interview only.)  

More than one-third of participants described pain in five or more sites. Over the subsequent 7 years, participants with persistent pain were more likely to experience declines in physical function (64% persistent pain, 59% intermittent pain, 57% no bothersome pain) and well-being (48% persistent pain, 45% intermittent pain, 44% no bothersome pain), but were not more likely to experience cognitive decline (25% persistent pain, 24% intermittent pain, 23% no bothersome pain).

“The findings from this study point to the importance of access to effective treatment for persistent pain in older adults and the need for additional research in chronic pain to optimise quality of life,” said lead author Christine Ritchie, MD, MSPH, of Massachusetts General Hospital.

Source: Wiley

Categories : Ageing COVIDTags :

COVID Deadlier than Bacterial or Viral Pneumonia for Older ICU Patients

On By ModernMedia
Source: National Cancer Institute on Unsplash

For older patients in intensive care units (ICUs), COVID is more severe than bacterial or viral pneumonia, suggests new research published in the Journal of the American Geriatrics Society.

Among 11 525 patients aged 70 years and older who were admitted to Dutch ICUs, ICU-mortality and hospital-mortality rates of patients admitted with COVID were 39.7% and 47.6%, respectively. These rates were higher than the mortality of patients admitted because of pneumonia from causes other than COVID. (ICU- and hospital-mortality rates of patients admitted with bacterial pneumonia were 19.1% and 28.8%, respectively, and with viral pneumonia were 22.7% and 31.8%, respectively). Differences persisted after adjusting for several clinical characteristics and intensive care unit occupancy rate.

“In ICU-patients aged 70 years and older, COVID is more severe – with approximately double mortality rates – compared with bacterial or viral pneumonia. Nevertheless, more than half of these older patients admitted to Dutch ICUs with COVID survived the hospital,” said corresponding author Lenneke E. M. Haas, MD, PhD, of Diakonessenhuis, in the Netherlands. “Our findings provide important additional data to include in informed goals-of-care discussions.”

Source: Wiley

Categories : Ageing Neurodegenerative DiseasesTags :

Hearing Loss Linked to Dementia Risk

On By ModernMedia

A nationally representative study published in JAMA found that older adults with greater severity of hearing loss were more likely to have dementia, but the likelihood of dementia was lower among hearing aid users compared to non-users.

The findings are consistent with prior studies showing that hearing loss might be a contributing factor to dementia risk over time, and that treating hearing loss may lower dementia risk.

“This study refines what we’ve observed about the link between hearing loss and dementia, and builds support for public health action to improve hearing care access,” says lead author Alison Huang, PhD, MPH, a senior research associate in the Bloomberg School’s Department of Epidemiology and at the Cochlear Center for Hearing and Public Health, also at the Bloomberg School.

Hearing loss is a critical public health issue affecting two-thirds of Americans over 70. The growing understanding that hearing loss might be linked to the risk of dementia, which impacts millions, and other adverse outcomes has called attention to implementing possible strategies to treat hearing loss.

For the new study, Huang and colleagues analysed a nationally representative dataset from the National Health and Aging Trends Study (NHATS). Funded by the National Institute on Aging, the NHATS has been ongoing since 2011, and uses a nationwide sample of Medicare beneficiaries over age 65, with a focus on the 90-and-over group as well as Black individuals.

The analysis covered 2413 individuals, about half of whom were over 80 and showed a clear association between severity of hearing loss and dementia. Prevalence of dementia among the participants with moderate/severe hearing loss was 61% higher than prevalence among participants who had normal hearing. Hearing aid use was associated with a 32% lower prevalence of dementia in the 853 participants who had moderate/severe hearing loss.

The authors note that many past studies were limited in that they relied on in-clinic data collection, leaving out vulnerable populations that did not have the means or capacity to get to a clinic. For their study, the researchers collected data from participants through in-home testing and interviews.

How hearing loss is linked to dementia isn’t yet clear, and studies point to several possible mechanisms. Huang’s research adds to a body of work by the Cochlear Center for Hearing and Public Health examining the relationship between hearing loss and dementia.

Source: Johns Hopkins Bloomberg School of Public Health

Categories : AgeingTags :

Areas with Age Bias Associated with Greater Longevity

On By ModernMedia
Photo by Bennett Tobias on Unsplash

Older adults living in areas with greater age bias had better health outcomes than those in areas with less bias, according to a study published in Social Science & Medicine. These findings came as a surprise to the researchers, who were expecting the reverse.

“Quite the opposite of what we expected emerged,” says senior author Allecia Reid, associate professor of social psychology and senior author of the paper published in the journal . “Rather than dying earlier in counties with more negative attitudes toward older adults, we found in fact that older adults were living longer in counties with more negative attitudes towards older adults.”

University of Massachusetts Amherst researcher Reid and colleagues had based their hypothesis on earlier research showing that minority groups, such as African Americans and sexual minorities, have worse health outcomes in counties with more negative attitudes toward their group.

“We were thinking, similar to those findings, that in counties with more negative attitudes towards older adults, we would see them being likely to die earlier than in counties with more positive attitudes toward residents 65 and older,” Reid says. “Contrary to what we thought, something positive is happening in these ageist communities that is helping them live longer, healthier lives.”

The only other study examining community-level age bias and older adults’ health found that explicit age bias was linked to positive health behaviours among older adults, while implicit bias was linked to negative health behaviours among older adults.

The UMass Amherst researchers analysed data on more than one million Americans who reported their explicit bias and taken an implicit bias test between 2003 and 2018

Based on that data, the team developed aggregate estimates at the county level about how much residents like older adults. Then they linked that with the county’s death rates for individuals age 65+. Counties with higher explicit age bias had lower mortality, or 87.67 fewer deaths per 100 000 residents. In contrast, implicit bias was not associated with mortality outcomes.

“The explicit age bias-mortality association was only evident in communities with younger populations but did not depend on community ethnic composition,” the paper states.

The researchers looked at ways that the more ageist communities might be doing things that helped maintain the health of older adults. They found that greater explicit age bias also was associated with lower death rates among young and middle-aged adults in those counties, suggesting that any health benefits of living in ageist communities may begin to accrue in earlier life.

In addition, “communities with higher explicit age bias also had higher rates of exercise…, better general health…, and more days of good mental health,” the paper states. These findings point to potential pathways through which ageist communities may promote health. However, the researchers also note that factors they were unable to examine, such as better medical care and more green spaces, may also explain associations of community age bias with better health.

Reid says the surprising findings point to more areas of examination which may lead to improved longevity for all communities.

“Can we figure out what is happening in these more ageist communities that seems to be potentially promoting both better mental health and better longevity,” she says. “And if we can pinpoint those things, then that’s a flag for all communities to think about.”

Source: University of Massachusetts Amherst

Categories : AgeingTags :

Friendly ‘Zombie’ Cells Help Promote Tissue Repair

On By ModernMedia
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

On By ModernMedia
Photo by Adam Birkett on Unsplash

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