Molecules that promise to slow ageing

by Hansraj Agrawal | Jun 24, 2023 | Science

You may know metformin as a diabetes drug and rapamycin as a cancer drug, but clinical trials are underway to determine their efficacy as anti-ageing supplement s, too. The search for more such potential anti-ageing molecules is on around the world.

A recent study involving mice, worms, and monkeys found that as the animals grew older they had less taurine, an amino sulphonic acid present in animal tissue. The study — titled ‘Taurine deficiency as a driver of ageing’ — further found that with taurine supplements the ageing effects could be reversed, leading to longer, healthier lives.

“And then we looked at humans,” says Vijay K Yadav, Assistant Professor, Columbia University, New York. “We measured taurine and its metabolite levels in 12,000 people to see whether taurine in abundance in the blood of humans correlates with the health of 60-year-old humans.” It was found that those with high taurine levels were healthier in numerous ways, including lower rates of obesity, diabetes and cholesterol.

“This is an exciting phase for ageing interventions. In the next few years, we will have an anti-ageing basket of different molecules as a way forward for precision medicine,” says Yadav.

Researchers are spreading the net far and wide. “Indolepropionamide, resveratrol, and urolithin A are some of the molecules being tested by researchers for anti-ageing effects,” said Prasad Kasturi, Assistant Professor, IIT-Mandi, Himachal Pradesh.

Ageing is frequently linked to disease. Cellular senescence, where damaged cells stop dividing, plays a role in ageing. These senescent cells can cause damage to the body by releasing harmful proteins.

Chemical pathway

“There are a lot of promising molecules that are entering clinical phases. Rapamycin is in small clinical trials, as also a number of senolytics,” says Pankaj Kapahi, Professor, The Buck Institute for Research on Aging, Novato, California. Senolytic drugs can eliminate senescent cells and this, in turn, may help prevent or treat age-related diseases in humans.

Kapahi’s research, which is likely to enter clinical trial this year, is titled ‘Glycation-lowering compounds inhibit ghrelin signalling to reduce food intake, lower insulin resistance, and extend lifespan’. According to the paper, glycolysis (breakdown of glucose by enzymes) can cause the build-up of a substance called methylglyoxal (MGO), which is linked to obesity and ageing issues.

Kasturi says it’s difficult to say more about the anti-ageing molecules under trial right now because “most of the time we don’t know the exact nature of the molecules that are under a clinical trial, but we have a wide variety of chemicals or molecules, chemical sensing molecules, natural molecules, phytochemicals, and a number of molecules that are known to modify lifespan in different model organisms”.

Kapahi says the ongoing efforts are mostly small-scale clinical trials in Phase I or II.

There are several common molecules that are potential candidates for studies related to anti-ageing. The diabetes drug metformin, for instance, is being investigated under a study titled ‘Metformin in ageing and ageing-related diseases: clinical applications and relevant mechanisms’. The findings suggest that metformin may slow the ageing process and provide protective benefits against the advancement of age-related diseases by influencing crucial events like protein maintenance, altered cell communication, changes in gene activity brought by environmental factors, and so on.

Rapamycin, used in cancer treatment, is considered another potential candidate for an anti-ageing drug. The research titled ‘Rapamycin treatment increases survival, autophagy biomarkers, and expression of the anti-ageing klotho protein in elderly mice’ suggests that rapamycin has a positive effect on ageing mice by boosting autophagy — the process that cleans up waste in cells, and cuts down harmful senescent cells.

In the study, two-year-old mice received rapamycin or a placebo. With rapamycin they survived the 12-week period, whereas 43 per cent of the control group died. Rapamycin caused slight weight loss and showed potential for reducing the inflammatory markers linked to ageing.

Health span

Can science then reverse ageing ?

“We need to do the experiments to better understand which molecules target which age-related pathologies. There is unlikely to be one silver bullet that will simply solve ageing. The basic science in the field will need to progress hand-in-hand to deliver better therapeutic targets to extend a healthy lifespan,” says Kapahi.

Parminder Singh, another researcher at the Buck Institute for Research on Ageing, says, “The main goal of ageing research is to extend healthy span, not lifespan per se. The idea is not to just add 10 extra years to your life; I think the idea is to, you know, improve your health span as well.”

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When diseases attack in deadly groups

by Hansraj Agrawal | Jun 24, 2023 | Science

A recent study conducted in rural India has revealed that three out of five people suffer from chronic health issues. The study by The George Institute of Global Health highlights the prevalence of multimorbidity (more than one health condition in an individual) in rural India and the urgent need for comprehensive healthcare solutions.

The authors of the report — Dr Balaji Gummidi, Vaishali Gautam, Dr Oommen John, Arpita Ghosh, and Dr Vivekanand Jha — analysed the self-reported health of individuals in a rural region of Andhra Pradesh to investigate the prevalence and causes of multimorbidity. The team studied non-communicable diseases, communicable diseases, and mental illnesses.

The findings showed that more than one-fourth (around 28 per cent) of the rural population suffered from a combination of diabetes and high blood pressure, while nearly 8 per cent dealt with diabetes, high blood pressure, and kidney disease. In the case of non-cardiometabolic diseases, about 44 per cent experienced two co-existing conditions: acid reflux and musculoskeletal diseases.

A key finding was that diabetes and high blood pressure were closely associated with chronic kidney disease rather than heart disease — highlighting a link that was not commonly known before. The study identified depression and anxiety as integral components of multimorbidity in rural India.

Dr Jha, Executive Director at George Institute, pointed out that multimorbidity in rural India was associated with advancing age, the feminine gender, and obesity. Gender-specific differences emerged, too, with a higher prevalence of stroke and heart failure seen in men, while more women reported suicidal thoughts. These differences may stem from a combination of biological and lifestyle factors.

Young and unhealthy

The study also highlighted the prevalence of multimorbidity among the younger working population, which throws up unique challenges. Unlike older individuals, younger people are less inclined to accept the need for multiple medications. Consequently, the concept of ‘multipills’ — combination pills that target multiple diseases — becomes crucial in managing multimorbidity, particularly among the youth. While multipills are already available for conditions such as musculoskeletal diseases and gastrointestinal ailments, more are needed to address other multimorbidities.

Another common problem in rural areas, Dr Gummidi pointed out, is that of ‘multi-pharmacy’. Patients often visit multiple doctors for various ailments, resulting in prescriptions of different medications for the same disease and the risk of overdose and associated complications.

A resilient healthcare system that addresses complex illnesses and their causes must grasp the implications of multimorbidity, shifting the focus from treating individual diseases to treating clusters of diseases. This holistic approach can improve patient outcomes and create a healthier future for all, he says.

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Acute inflammation control

by Hansraj Agrawal | Jun 10, 2023 | Science

A new study has found that inhibitors of monoamine oxidases (MAOs), a family of enzymes that catalyse the oxidation of amines, may be repurposed for treating acute inflammation and used as a novel therapeutic target to develop a new class of anti-inflammatory agents.

Available drugs for inflammation target the “housekeeping enzyme” that preserves the normal physiological function called peripheral cyclooxygenase (COX-1, COX-2) enzymes. Most non-steroidal anti-inflammatory drugs (NSAIDs) control the five signs of inflammation by compromising the body’s normal homeostasis. Thus, biomedical scientists are constantly exploring novel targets for inflammation management.

Taking a cue from earlier studies that showed MAO inhibitors (MAOI), used for depression, significantly reduced joint pain and stiffness, scientists from the Institute of Advanced Study in Science and Technology (IASST), Guwahati, used an experimental animal model to repurpose MAOI as a new therapeutic target to develop novel anti-inflammatory drugs.

The researchers, led by Associate Professor Asis Bala, have explored the role of MAO mediated pathway in acute inflammation in an experimental animal model, says a press release.

The investigation found that MAO inhibitors may be re-profiled for treating acute inflammation.

The scientists have also experimentally proved that the MAO enzyme, a group of flavoenzymes that catalyse the oxidative deamination of dietary amines and biological amines, may be used as a novel therapeutic target to develop a new class of anti-inflammatory agents, the release says.

Dessication-tolerant hotspot

India’s biodiversity hotspot Western Ghats is home to 62 desiccation-tolerant vascular plant species, which could have applications in agriculture, particularly in areas with water scarcity. Vascular plants have vascular tissues — xylem and phloem — for transportation of water and nutrients.

Desiccation-tolerant (DT) vascular plants can withstand extreme dehydration, losing up to 95 per cent of their water content, and they revive themselves once water is available again. This allows them to survive in arid environments. In tropical regions, they are the predominant occupants of rock outcrops.

In India, DT plants have been relatively understudied. A recent study by scientists from Agharkar Research Institute, Pune, identified 62 DT species in the Western Ghats, way more than the nine known species previously.

The research, published in the Nordic Journal of Botany, includes an inventory of species with their habitat preferences. Sixteen species are Indian endemic, and 12 are exclusive to Western Ghats outcrops, highlighting the region’s importance as a global DT hotspot. In addition to rock outcrops, tree trunks in the partially shaded forests were also found to be crucial habitats for DT species, as per the study.

Nine genera of DT plants have been reported as new, with Tripogon capillatus representing the first record of an epiphytic DT angiosperm. The study also provides the first field observation-based proof of the DT properties of the gesneriad Corallodiscus lanuginosus. A time-lapse video records the hydration process of this species.

The team, led by Dr Mandar Datar and comprising Smrithy Vijayan, Aboli Kulkarni, and Bhushan Shigwan, collaborated with Dr Stefan Porembski, from Rostock University Germany, who is recognised as an expert on tropical rock outcrops.

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Can you chant yourself into a deep, peaceful slumber?

by Hansraj Agrawal | Jun 10, 2023 | Science

A study by researchers from IIT-Mandi, IIT-Roorkee, Yale University (USA), University of Tubingen (Germany), and Brain Wave Science, Inc (USA), suggests that chanting the Hare Krishna mantra along with cognitive behavioural therapy (CBT) may be a cost-effective alternative to insomnia treatment. The ‘Hare Krishna mantra-based cognitive therapy (HMBCT)’ includes sleep restriction therapy, stimulus control therapy, and sleep hygiene, along with an audible mantra chanting-based training.

The results of the study were published in the Journal of Sleep Research and Therapy. The paper has been co-authored by Prof Laxmidhar Behera, Director, IIT-Mandi; Dr Tharun Kumar Reddy, Assistant Professor, Department of Electronics and Communication Engineering, IIT-Roorkee; and Dr Chandan Kumar Behera, Postdoctoral Associate, Yale University School of Medicine; Prof Niels Birbaumer, Director, Institute of Medical Psychology and Behavioural Neurobiology, University of Tubingen; and Dr Krishna Ika, President and CEO, Brain Wave Science, Inc, Southborough, USA.

Insomnia is a sleep disorder that affects millions of people worldwide and is characterised by difficulty falling asleep, or staying asleep, or both. Traditional CBT is a common treatment for insomnia, but it can be expensive and time-consuming. The researchers aimed to evaluate a novel, cost-effective alternative therapy that includes mantra chanting.

Explaining the rationale behind the research, Dr Laxmidhar Behera said, “Different spiritual traditions promote the use of chanting for spiritual awareness. Islam has prescribed prayers called Salah, while Christianity has the Gregorian chant. The Vedas, a large body of ancient Indian literature, describe the Hare Krishna mantra as a tool to purify the mind. Anecdotal reports have suggested that mantra meditation could improve sleep quality in primary insomnia subjects.”

The researchers conducted a pilot study to establish the groundwork for a larger study. They administered HMBCT therapy to one group of participants while another group listened to soothing music.

The six-week pilot study involved 48 male participants from varied faiths. Each week, the participants in the therapy group received six 45-minute sessions of HMBCT in the evening and were asked to practise the therapy on the evenings of sleep recording.

Sleep quality was assessed using behavioural measures, sleep logs, and sleep recordings before and after the treatment period. The results showed that HMBCT significantly improved sleep quality measures, including a 61 per cent reduction in Epworth Sleepiness Scale (ESS) scores and an 80 per cent reduction in Insomnia Severity Index (ISI) scores.

Participants did not take any sleep-inducing medication during the study.

The findings suggest that adding mantra chanting to traditional CBT may improve sleep quality.

Dr Reddy cautions that more research is needed to confirm the efficacy of HMBCT in treating insomnia.

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How a healthy gut adds years to your life

by Hansraj Agrawal | Jun 10, 2023 | Science

The impact of gut microbiomes on health, specifically neurological conditions, has gained significant attention in recent times. One particular metabolite, butyrate, has emerged as a crucial element in promoting brain health through the gut-brain axis.

“Without an externally administered synthetically produced butyrate as a supplement, we are able to make the human body produce its own butyrate by balancing the gut microbiome, which is probably a first in the world,” said one of the researchers, Samuel JK Abraham, Faculty of Medicine, Yamanashi University, Japan.

However, it is important to note that different pathways of butyrate production can lead to varying effects, including some that are detrimental. Maternal butyrate supplementation has also shown detrimental effects on offspring.

Researchers have been studying pullulans, beta-glucans produced by the yeast-like fungus Aureobasidium pullulans, which are found to help multiply butyrate-producing bacteria in the gut. (Beta-glucans are a group of polysaccharides, or complex carbohydrates, that are found in the cell wall of fungi, bacteria, and plants. Pullulan is a linear polysaccharide composed primarily of glucose units.)

“Butyrate being the single most demarcating factor between the longest living and the shortest, we can produce it not by a synthetic supplement, or a naturally produced supplement, but rather by making the gut environment good. So that is the most natural way towards a healthy, enduring, long life,” says Abraham.

Biological response modifier beta-glucans (BRMGs) such as nichi glucan have demonstrated anti-inflammatory effects in Covid-19 cases, anti-fibrotic effects in fatty liver disease, and improvements in behaviour and sleep patterns in people with autism spectrum disorder (ASD).

To further investigate the effects of nichi glucan, a randomised clinical study was undertaken involving 18 people with ASD, with one group receiving only conventional treatment and the other receiving nichi glucan supplementation.

The results showed that, from an abundance, the presence of enterobacteriaceae (which causes life-threatening complications) decreased significantly in the group receiving nichi glucan, while it increased in the control group. Changes were also observed at the species level, with decreases in harmful bacteria and increases in beneficial bacteria.

“These findings suggest that AFO-202 beta 1,3-1,6 glucan, produced by Aureobasidium pullulans, not only balances the gut microbiome in children with ASD but also potentially plays a prophylactic role in Parkinson’s and Alzheimer’s diseases,” the study showed.

The study also highlights the role of gut microbiota in health. Understanding the composition and function of gut microbiota in different populations and conditions can provide valuable insights for developing targeted interventions to improve health outcomes.

Live human study

A recent study titled ‘Gut microbiota differences in elderly individuals: A comparison between rural city Kyotango and urban city Kyoto’ explored the gut microbiota of older healthy individuals in two Japanese cities. The study revealed notable distinctions in the composition of gut microbes, highlighting the possible connection between gut microbiota and longevity.

The study, conducted by researchers from a Japanese university, involved 102 participants — 51 from Kyotango and 51 from Kyoto — matched by age and gender. Faecal samples were collected from each participant and analysed using 16S ribosomal RNA gene sequencing to determine the diversity, abundance, and function of their gut microbiota.

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Precise cellular delivery

by Hansraj Agrawal | May 28, 2023 | Science

Researchers at IIT-Madras have developed a technique to deliver large-sized biomolecules into live cells using infrared laser pulses.

This technology, known as ‘photoporation’ or ‘optoporation’, is a safe and effective method to transport molecules into cells for potential use in disease diagnosis and treatment.

Biomolecules are essential chemicals produced and utilised by living organisms, and form the basic building blocks of life. Nucleic acids, a specific type of biomolecule, make up the genetic material (RNA and DNA) in living organisms. The introduction of nucleic acids into living cells is called ‘transfection.’

Researchers worldwide are investigating multiple transfection techniques such as microinjection, electroporation (using an intense electric field to introduce small molecules into cells), and photoporation.

The team at IIT-Madras has been working to develop devices that perform parallel high-throughput photoporation for cellular therapy and diagnostics.

This method involves using a light, directly or indirectly, to create temporary nano pores in the cell membrane, allowing for the delivery of biomolecules like drugs, genes, and proteins.

“It is a precise and non-invasive technique that provides higher efficiency with lower toxicity and less damage to cells,” says Dr Tuhin Subhra Santra, associate professor, Department of Engineering Design, IIT-Madras.

The researchers created a titanium micro-ring device to be placed near the monolayer cells into which the molecules must be introduced.

When the micro-ring is exposed to infrared laser, photothermal bubbles are produced on its surface.

The bubbles are induced on the cell membrane; when they collapse, the resulting jet flow in the vicinity of the cell membrane creates nanopores.

Toughened bio-material

Dr Paramita Das, assistant professor at the Functional Nanocomposites Lab, Department of Chemical Engineering, IISER, Bhopal, has developed ‘ternary nanoparticles’ from biological materials such as carboxymethyl cellulose polymer. Ternary nanocomposites are composed of three distinct components at the nanoscale. These components typically include two types of nanoparticles and a matrix material that surrounds and binds them together.

Ternary nanocomposites exhibit unique properties arising from the synergistic interactions between the three components.

“These ternary nanocomposite films are not only flexible but also exhibit high tensile strength, stiffness, and toughness, and could be placed among the top end of the CNC-based bouligand-structured nanocomposites,” says a note from IISER, Bhopal.

Ternary nanocomposites have a wide range of applications in electronics, energy storage, catalysis, sensors, coatings, and biomedical engineering.

By manipulating the composition, size, shape, and distribution of the nanoparticles within the matrix material, researchers can design ternary nanocomposites with specific properties for different applications.

Today there is a need for high-performance, mechanically strong and lightweight engineering materials for various applications, including packaging, structural engineering, transportation, energy, environment, and aerospace.

Biological materials have outstanding mechanical properties because of the combination of multiple building blocks and sophisticated hierarchical arrangements at various length-scales, the paper says.

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