Nowadays, HIV+ patients have an expected lifespan that is only slightly shorter than healthy individuals. For this reason, along with the fact that infection can be acquired at a relatively advanced age, the effects of ageing on HIV+ people have begun to be evident. Successful anti-viral treatment is, on one hand, responsible for the development of side effects related to drug toxicity; on the other hand, it is not able to inhibit the onset of several complications caused by persistent immune activation and chronic inflammation. Therefore, patients with a relatively advanced age, i.e. aged more than 50 years, can experience pathologies that affect much older citizens. HIV+ individuals with non-AIDS-related complications can thus come to the attention of clinicians because of the presence of neurocognitive disorders, cardiovascular diseases, metabolic syndrome, bone abnormalities and non-HIV-associated cancers. Chronic inflammation and immune activation, observed typically in elderly people and defined as ‘inflammaging’, can be present in HIV+ patients who experience a type of premature ageing, which affects the quality of life significantly. This relatively new condition is extremely complex, and important factors have been identified as well as the traditional behavioural risk factors, e.g. the toxicity of anti-retroviral treatments and the above-mentioned chronic inflammation leading to a functional decline and a vulnerability to injury or pathologies. Here, we discuss the role of inflammation and immune activation on the most important non-AIDS-related complications of chronic HIV infection, and the contribution of aging per se to this scenario
The aim of the study was to evaluate longitudinal associations between HbA1c levels, diabetes status and subsequent cognitive decline over a 10 year follow-up period.
Data from wave 2 (2004–2005) to wave 7 (2014–2015) of the English Longitudinal Study of Ageing (ELSA) were analysed. Cognitive function was assessed at baseline (wave 2) and reassessed every 2 years at waves 3–7. Linear mixed models were used to evaluate longitudinal associations.
The study comprised 5189 participants (55.1% women, mean age 65.6 ± 9.4 years) with baseline HbA1c levels ranging from 15.9 to 126.3 mmol/mol (3.6–13.7%). The mean follow-up duration was 8.1 ± 2.8 years and the mean number of cognitive assessments was 4.9 ± 1.5. A 1 mmol/mol increment in HbA1c was significantly associated with an increased rate of decline in global cognitive z scores (−0.0009 SD/year, 95% CI −0.0014, −0.0003), memory z scores (−0.0005 SD/year, 95% CI −0.0009, −0.0001) and executive function z scores (−0.0008 SD/year, 95% CI −0.0013, −0.0004) after adjustment for baseline age, sex, total cholesterol, HDL-cholesterol, triacylglycerol, high-sensitivity C-reactive protein, BMI, education, marital status, depressive symptoms, current smoking, alcohol consumption, hypertension, CHD, stroke, chronic lung disease and cancer. Compared with participants with normoglycaemia, the multivariable-adjusted rate of global cognitive decline associated with prediabetes and diabetes was increased by −0.012 SD/year (95% CI −0.022, −0.002) and −0.031 SD/year (95% CI −0.046, −0.015), respectively (p for trend <0.001). Similarly, memory, executive function and orientation z scores showed an increased rate of cognitive decline with diabetes.
Significant longitudinal associations between HbA1c levels, diabetes status and long-term cognitive decline were observed in this study. Future studies are required to determine the effects of maintaining optimal glucose control on the rate of cognitive decline in people with diabetes.
Scientists have made a discovery that could lead to a revolutionary drug that reverses ageing.
Experiments from a team at the University of New South Walessuggest a treatment is possible to repair DNA damage from both ageing and radiation. The ‘call signaling’ molecule is called NAD+. NAD+ is naturally in every cell of the body and posseses a key role in protein interactions (which control DNA repair.).
When treating mice with an NAD+ ‘booster’ called NMN , studies showed improvement in the cells’ ability to repair the damaged DNA.
“This is the closest we are to a safe and effective anti-ageing drug that’s perhaps only three to five years away from being on the market if the trials go well. In the study, cells of old mice were indistinguishable from the young mice after just one week of treatment,” said lead author Professor David Sinclair.
Professor Sinclair pictured in the middle.
The work has also drawn the attention of NASA which is interested in its uses in the challenge of keeping astronauts healthy while in space. On short missions, astronauts experience accelerated ageing due to exposure from cosmic radiation, suffering from muscle weakness, memory loss and other symptoms when they return. On longer missions, like a trip to Mars, the situation would be far worse. Five per cent of the astronauts’ cells would die and their chances of cancer would approach near 100 per cent.
Professor Sinclair and his colleague Dr Lindsay Wu were winners in NASA’s iTech competition in December last year:
‘We came in with a solution for a biological problem and it won the competition out of 300 entries,’ Dr Wu said.
Cosmic radiation isn’t an issue exclusive to astronauts. We are all exposed to radiation aboard aircraft. A London-Singapore-Melbourne flight is equivalent in radiation to a chest x-ray.
The other group that could benefit from this work is survivors of childhood cancers. 96 percent of childhood cancer survivors suffer a chronic illness by age 45. This includes cardiovascular disease, Type 2 diabetes, Alzheimer’s disease, and certain forms of cancer.
There may be a connection between tau proteins, which are linked to Alzheimer’s, and insulin resistance.
People with lifestyle-related diabetes are at an increased risk of developing dementia and, with both conditions on the rise, scientists are scrambling to understand their connection in the hope of finding new treatments.
There are 54 million people in Europe living with lifestyle-related – or Type 2 – diabetes and the numbers are soaring, fuelled by the obesity epidemic. Alzheimer’s, the most common form of dementia, affects around 10.5 million Europeans and this number is forecast to hit 18.7 million by 2050 as a result of population ageing.
People with Type 2 diabetes have higher levels of sugar in their blood because their cells have become resistant to insulin which normally regulates blood sugars. Insulin resistance in the brain has been linked to dementia in large, long-term studies but the exact mechanism behind the phenomenon is still being teased out.
‘There is growing evidence from epidemiological studies suggesting that Type 2 diabetes is a risk factor for dementia, particularly Alzheimer’s disease,’ said Dr Shreyasi Chatterjee at the University of Southampton, UK. ‘Therefore, we want to know more about the relationship between insulin resistance seen in diabetes and the protein build-up associated with Alzheimer’s.’
Key to solving these puzzles are two proteins associated with memory loss in Alzheimer’s – amyloid-beta, which accumulates in plaques that trigger brain cell death, and tau proteins, which cause tangles in the brain.
‘Insulin resistance in the brain can make it difficult for Alzheimer’s patients to process the sugar which is needed to fuel brain cells,’ said Dr Chatterjee. ‘It disrupts normal signalling pathways in the brain and can also hamper the brain’s natural mechanism for clearing misfolded proteins that trigger memory loss.’
As part of the EU-funded AlzDiabetes project, Dr Chatterjee is focusing on the role of tau proteins in fruit flies that have been genetically programmed to mimic the kind of neurodegeneration seen in Alzheimer’s disease.
Fruits flies are often used in genetic research as they have around 75 % of the genes that cause human disease and they are easy to work with thanks to their short breeding times. Dr Chatterjee worked with a population of fruit flies bred to have excessive tau proteins, and experimented with adding insulin receptor substrate (IRS) – a key player in processing insulin.
‘We could reduce the likelihood that people with Type 2 diabetes will develop Alzheimer’s.’
Prof Yifat Miller, Ben-Gurion University of the Negev in Israel
She found that adding IRS gave the fruit flies better memories and longer lifespans, whereas knocking out the gene that produces it increased the level of tau proteins. This new observation is the most direct evidence to date of a direct connection between insulin resistance seen in diabetes and the tau tangles seen in Alzheimer’s disease.
Her team also observed that when the flies were insulin resistant their brains were unable to clear away the toxic tau proteins, providing an explanation of why people with Type 2 diabetes might develop Alzheimer’s.
Curbing dementia risk
As scientists learn more about how insulin resistance affects the brain, researchers hope that controlling blood sugar in diabetic patients will curb their dementia risk.
‘We already know that treating Alzheimer’s disease with inhaled insulin (a diabetes medication) reduces cognitive impairment,’ said Dr Chatterjee. ‘Other diabetes drugs are now in clinical trials to test whether they could slow the progression of dementia.’
In addition to having a higher risk of Alzheimer’s, diabetes patients are also more likely than the average person to develop Parkinson’s disease. Professor Yifat Miller at the Ben-Gurion University of the Negev in Israel has explored the relationship between diabetes, Alzheimer’s and Parkinson’s as part of the EU-funded AbetaAlphasynTau project.
Her team used computer simulations to model the interactions at the molecular level between the amyloid-beta protein, which is associated with Alzheimer’s, alpha-synuclein, which builds up in the brains of Parkinson’s patients, and amylin, a hormone produced by the pancreas. The project pinpointed crucial fragments of these proteins that make them stickier when they interact.
We are now developing molecules that would inhibit these interactions,’ Prof. Miller said. ‘The new molecules will prevent the interactions between these proteins so that they will not clump together. Consequently, we could reduce the likelihood that people with Type 2 diabetes will develop Alzheimer’s and Parkinson’s later in life.’
Using their detailed molecular knowledge of these brain diseases, Prof. Miller’s team is designing molecules that could break the link between these three diseases. However, this is still in the early stages of drug design and several new medicines may be needed.
‘The inhibitor we are working on is not a single molecule but a cocktail of molecules,’ she said. ‘It’s very challenging but we are excited about laying the foundation for understanding how these diseases are connected.’
Study could explain why even with healthy lifestyles some people die younger than others, and raises future possibility of extending the human lifespan
Scientists have found the most definitive evidence yet that some people are destined to age quicker and die younger than others – regardless of their lifestyle.
The findings could explain the seemingly random and unfair way that death is sometimes dealt out, and raise the intriguing future possibility of being able to extend the natural human lifespan.
“You get people who are vegan, sleep 10 hours a day, have a low-stress job, and still end up dying young,” said Steve Horvath, a biostatistician who led the research at the University of California, Los Angeles. “We’ve shown some people have a faster innate ageing rate.”
A higher biological age, regardless of actual age, was consistently linked to an earlier death, the study found. For the 5% of the population who age fastest, this translated to a roughly 50% greater than average risk of death at any age.
Intriguingly, the biological changes linked to ageing are potentially reversible, raising the prospect of future treatments that could arrest the ageing process and extend the human lifespan.
“The great hope is that we find anti-ageing interventions that would slow your innate ageing rate,” said Horvath. “This is an important milestone to realising this dream.”
Horvath’s ageing “clock” relies on measuring subtle chemical changes, in which methyl compounds attach or detach from the genome without altering the underlying code of our DNA.
His team previously found that methyl levels at 353 specific sites on the genome rise and fall according to a very specific pattern as we age – and that the pattern is consistent across the population. The latest study, based on an analysis of blood samples from 13,000 people, showed that some people are propelled along life’s biological tramlines much quicker than others – regardless of lifestyle.
“We see people aged 20 who are fast agers and we look at them 20 years later and they are still fast agers,” said Horvath. “The big picture here is that this is an innate process.”
The scientists found that known health indicators, such as smoking, blood pressure and weight, were still more valuable in predicting life expectancy in the 2,700 participants who had died since the study began, but that their underlying aging rate also had a significant effect.
In a fictional example, the scientists compare two 60-year-old men, Peter, whose ageing rate ranks in the top 5% and Joe, whose rate is in the slowest 5%. If both are smokers and have stressful jobs, Peter is given a 75% chance of dying in the next 10 years compared to a 46% chance for Joe.
This is not the first time that scientists have observed so-called epigenetic changes to the genome with age, but previously these were put down to wear-and-tear brought about by environmental factors, rather than indicating the ticking of an internal biological clock.
Wolf Reik, a professor of epigenetics at the University of Cambridge who was not involved in the work, said: “It now looks like you get a clock given to you when you’re young. It gets wound up and the pace it’s ticking at is dictated by this epigenetic machinery.”
“I’m sure insurance companies are already quite interested in this kind of thing,” he added.
Horvath said he has no plans to market the test, which costs around $300 per sample in his lab, but admits he has run his own blood through the analysis.
“I’m currently 48 and the test indicated I was 5 years older, which I wasn’t too pleased about,” he said, but adds that for an individual factors like blood pressure and smoking were more decisive. “My innate ageing rate is too fast to become a centenarian, but otherwise I’m not too worried about it.”
The study, published in the journal Aging, suggests that accelerated ageing rather than simply a riskier lifestyle could explain why men die younger. Even by the age of five, Horvath said, the different speeds of aging between genders was apparent and by the age of 40 a biological age gap of 1-2 years opens up. “Women always age a little bit more slowly than men,” he said. “It’s not lifestyle it’s this innate ageing process that favours women.”
The team picked super-fit amateur cyclists between 55 and 79 and tested a wide range of physical functions commonly associated with ageing such as aerobic fitness, resting heart rate, skeletal mass, breathing ability and muscle density.
They were hoping to discover whether specific physiological markers could be used to determine age. But they found that it was difficult to tell who was older.
“If you couldn’t see these people many of these functions would point them to a much younger age,” said Professor Stephen Harridge, Director of the Centre of Human & Aerospace Physiological Sciences at Kings College.
“By exercising you do what your body wants it to do and are allowing to age optimally.
“So it is not ageing itself which brings about poor function and frailty, but the fact that people have stopped exercising and are no longer active.”
The 84 male and 41 female cyclists picked for the study had to be able to cycle 100km in under 6.5 hours and 60km in 5.5 hours, respectively, to be included in the study.
Smokers, heavy drinkers and those with high blood pressure or other health conditions were excluded.
The cyclists underwent two days of laboratory testing at King’s which measured cardiovascular, respiratory, neuromuscular, metabolic, endocrine and cognitive functions, bone strength, and health and well-being.
Volunteers’ reflexes, muscle strength, oxygen uptake during exercise and peak explosive cycling power were also measured.
The results of the study showed that in these individuals, the effects of ageing were far from obvious, with people of different ages having similar levels of function such as muscle strength, lung power and exercise capacity.
The maximum rate of oxygen consumption showed the closest association with age, but even this marker could not identify with any degree of accuracy the age of any given individual.
In a basic test which measured the time taken to stand from a chair, walk three metres, turn, and sit back down, even the oldest cyclists were well within the range of healthy young adults.
Although the researchers chose cyclists most other forms of aerobic activity would produce similar results.
Emeritus Professor Norman Lazarus, a member of the King’s team and also a cyclist, said: “Inevitably, our bodies will experience some decline with age, but staying physically active can buy you extra years of function compared to sedentary people.
“Cycling not only keeps you mentally alert, but requires the vigorous use of many of the body’s key systems, such as your muscles, heart and lungs which you need for maintaining health and for reducing the risks associated with numerous diseases.”
The new research was welcomed by charities who urged people to stay active.
Jane Tadman at medical research charity Arthritis Research UK said “The findings of this study back up our own research in the fact that many symptoms associated with ageing such as frailty are caused by being physical inactive. So many of our population are now living well into their 70s and 80s, and that should be a cause for celebration.
“But unless we can ensure that old age is spent in good health through remaining active, and this doesn’t necessarily meaning visiting the gym, it could be climbing the stairs on a regular basis, it will be a stage in life that is endured rather than enjoyed”.
“This study looks at aging in the context of the whole genome and gives us a more complete picture of what aging is,” said lead author Dr Brian Kennedy.
“Almost half of the genes we found that affect aging are conserved in mammals.
“In theory, any of these factors could be therapeutic targets to extend healthspan. What we have to do now is figure out which ones are amenable to targeting.”
To determine which genes were responsible for ageing, researchers examined 4,698 strains of yeast, each with a single gene deletion and then monitored how long cells lived for before they stopped dividing.
They found that deleting a gene called LOS1 produced particularly impressive results, extending life by 60 per cent. LOS1 is linked to a genetic master switch which has long been associated with calorie restriction through fasting and increased lifespan.
“Calorie restriction has been known to extend lifespan for a long time,” added Dr. Kennedy.
Co-author Dr Mark McCormick, of the Buck Institute said: “Our best results were single gene deletions that increased lifespan by around 60 per cent compared to normal yeast.”
Earlier this year academics from the University of Southern California found that a five day diet which mimics fasting can slow down ageing, add years to life, boost the immune system and cut the risk of heart disease and cancer.
Ageing is a topic best approached through the Microsoft mantra of “think global, act local” at many levels, because there is an ever-present danger of considering that ageing, and its inherent vulnerabilities, is something that happens to other people. Given the continuing compression of both morbidity and mortality, it is likely that the vast majority of us will live into old age, withincreasingly better levels of health than our parents and grandparents.
Yet we will also be confronted inevitably by age related disease and disability, and the challenge to geriatricians and gerontologists is to tease out and affirm the value to us all of our longevity—mindful of our vulnerability, but not allowing the discourse to be dominated by it.
My first local waypoint on ageing was the play showing during the congress in the municipal theatre in Villach: Simply Complicated, by Thomas Bernhard, one of Austria’s greatest dramatists. Centring around an old actor who is struggling with ageing and the outside world, Bernhard neatly catches the challenge that so many people view ageing, the most complex stage of our lives, in simplistic terms: “You’ll see that everything is complicated in this world. Everything looks easy, but it is very complicated. Everything is complicated.”
This is a good springboard for moving on to Paracelsus, the great German physician, whose family home is one of the highlights of a visit to Villach. Paracelsus is credited with, among many other innovations, unpicking the tenacious attachment of the medical establishment to Galenic theories of illnesses, and in particular to ageing. This too is a call to us to reject miserabilist tropes on ageing, and to incorporate simultaneous growth and loss of later life without diminishing our personhood.
However, the welcome reduction in incidence and enormous resources dedicated to biological treatments of dementia can distract us from the reality of helping people with dementia (and those of us who will develop the syndrome) in the present moment.
Klagenfurt was also the birthplace of Robert Musil, whose The Man Without Qualities is one of the great modernist classics of Austrian and world literature. Its central character, Ulrich, seeks a sense of life and reality but fails to find it, becoming “a man without qualities,” depending on the outer world to form his character. His struggle is a metaphor for our challenge to avoid characterising life with dementia in terms of life “without qualities,” and to be mindful that the outer world we offer to those with dementia is supportive of their search for meaningfulness.
Reaching further into the broader Germanophone literature provides prompts into how we might visualise the ongoing richness of life with cognitive impairment. We will have to wait until January 2017 for the English translation of the wonderful The Old King in His Exile by Arno Geiger, but particularly delightful insights are provided in Small World by the prolific Swiss author Martin Suter.
In this radical questioning we can draw inspiration from another great Austrian poet,Rainer Maria Rilke: “Live the questions now. Perhaps then, someday far in the future, you will gradually, without even noticing it, live your way into the answer.”
It is natural to look your age as you grow older. However, your skin age also depends on the kind of food you are consuming and an overdose of these foods can make you look older than you already are. Have a look