Age Tech World explores the latest research developments in ageing and longevity.
Shorter telomeres linked to increased risk of age-related brain diseases
Researchers have found evidence suggesting that healthier lifestyle choices could mitigate telomere length-associated risks.
The risk of stroke, dementia, and late-life depression (LLD) increases for people as they get older. Likewise, telomeres, which are protective caps on chromosomes, naturally shorten with age, or exposure to adverse environmental conditions, like stress and pollution, increasing the risk for DNA damage.
This study sought to determine the association between these age-related brain diseases and leukocyte telomere length (LTL), and whether LTL was a direct causal factor or merely a predictive marker for brain diseases.
To investigate this relationship, the research team analysed data from 356,173 participants in the UK Biobank. They also used the McCance Brain Care Score (BCS), which accounts for factors like blood pressure, blood sugar levels, cholesterol, and lifestyle behaviours, and social-emotional aspects that influence risk factor profiles.
Their findings showed that individuals with shorter LTLs and lower BCSs, reflecting less optimal lifestyle choices, were at greater risk for these brain diseases. Notably, those with shorter LTLs but healthier lifestyle scores (high BCS) did not show a significantly increased risk, suggesting that a high BCS may mitigate the effects of short telomeres.
One notable limitation of the study was that LTL was only measured at the initial visit, and so telomere shortening could not be tracked over time. Additionally, the study only included individuals of European descent, which limits its generalisability.
Nevertheless, reducing risk factors appears to mitigate the negative effects of shorter telomeres on cerebral health, which sets the stage for future studies to explore whether lifestyle interventions can in fact slow ageing’s effects on the brain.
Novel truncated RNAs from jumping DNA encode reverse transcriptases in ageing human brain
Scientists have recently reported real-world links in medical records associating common HIV drugs with a reduced incidence of Alzheimer’s disease.
The studies showed patients were at less risk of developing Alzheimer’s disease if they were taking drugs to block a famous enzyme called reverse transcriptase (RT), which copies RNA into DNA, opposite to the classical process.
To better understand the links between Alzheimer’s disease risk and people taking prescribed RT inhibitor drugs, researchers at Sanford Burnham Prebys looked for evidence of actual RT activity in the ageing human brain and in brains affected by Alzheimer’s disease, identifying RT enzymatic activity, and novel RNAs that encode brain RTs especially in neurons of the ageing human brain.
The scientists examined post-mortem brain tissue from donors who had died from Alzheimer’s disease and compared it to control samples without obvious disease.
RT activity was found within every brain sample, with a trend towards reductions in RT activity in the brains from terminal Alzheimer’s disease. This is consistent with the neuronal degeneration that is a hallmark of Alzheimer’s disease.
The scientists assessed multiple possible sources and identified long interspersed nuclear element-1 (LINE1), an ancient genetic sequence so common in mammalian genomes that it makes up nearly one-fifth of all human DNA.
It is normally inactive, but scientists have found rare forms that are active, using their own RTs to copy and paste themselves elsewhere in the genome.
In addition to uncovering abbreviated versions of LINE1, the scientists found that most of these variations contained only one of the two protein-coding regions that appear on a full-length transcript.
The scientists addressed their second major question regarding the types of cells with RT activity by comparing samples of neuron-rich gray matter with white matter that contains mostly glial cells.
They found that RT activity was significantly higher in gray matter, which the team say is consistent with RT activity being predominantly found in neurons;
Given the proven safety of FDA-approved RT inhibitor drugs, the researchers suggest that physicians and scientists should pursue prospective clinical trials studying these drugs’ effects on persons with early Alzheimer’s disease as a near-term approach to helping Alzheimer’s disease patients and their families.
Targeted immunotherapy for cancer could be used to tackle Alzheimer’s
Researchers have engineered immune cells that are equipped with specialised targeting devices called chimeric antigen receptors (CARs) that can distinguish and respond to tau tangles and various forms of toxic amyloid plaques – both of which are implicated in Alzheimer’s disease pathology.
The work, from researchers at the Buck Institute, has been inspired by advances in cancer therapy.
The team have carried out a proof-of-concept study which holds promise for precisely delivering therapeutic drugs directly to affected areas of the brain with fewer side effects.
The aim of the work is to turn immune cells into mobile biological drug factories that can “decide” when to release drugs at a site of pathology and, once cleared, can then move onto the next site of pathology.
While based on the same methods used to create targeted therapies for cancer, the researchers say there is a significant difference in the work as this technology does not involve the same toxicity seen in CAR-T cells, whereas these cells are designed to save neurons.
The suite of CARs have been built using pieces from well-known Alzheimer’s antibodies including those currently being tested in phase III clinical trials.
According to the team, these CARs allowed immune cells to detect tau tangles as well as different versions of amyloid beta, including Aβp3-42, which is more likely to clump together and resist being broken down.
The researchers say the technology goes beyond Alzheimer’s, and could be applicable to any disease that involves the immune system and extracellular aggregates.
Sensory impairment is vital for our understanding of dementia
A team of researchers are challenging the view that memory problems are the primary hallmark of dementia.
The team argues that changes in sensory perception such as vision and balance may be equally important indicators that many healthcare providers are currently missing.
The experts lay out the body of evidence supporting this shift in understanding in A New Approach to Dementia.
The lesser-known characteristics of dementia for some individuals include abnormalities such as altered visual and hearing perception, changes in hearing ability and sound processing, especially in noisy environments, diminished sense of smell and taste, and tactile sensitivity issues.
These changes in sensory and perceptual processing may accompany the more commonly recognised memory problems associated with conditions like Alzheimer’s disease.
This emerging understanding has significant implications for clinical practice and caregiving, and the authors suggest that incorporating comprehensive sensory and perceptual testing into standard diagnostic, care, support and management protocols could enable a better understanding of the experience of the person living with dementia and their signs and symptoms.
It could also lead to more targeted or personalised approaches, help maintain independence, and improve the quality of life for people living with dementia.
“This isn’t about replacing memory assessment, but rather expanding our toolkit to improve our capture of the full, more holistic, spectrum of dementia-related changes,” the researchers said.
Landmark study reveals survival limits of kidney transplantation in older patients
A major international study has revealed that the long-accepted survival advantage of deceased-donor kidney transplantation does not extend equally to every patient and every donor organ.
The large-scale analysis, drawing on data from the European Renal Association (ERA) Registry, examined five-year survival outcomes in 64,013 wait-listed adults across Catalonia, Denmark, France, Norway, and the UK who began dialysis between 2000 and 2019.
Using a robust target trial emulation (TTE) framework designed to mirror the structure of a randomised clinical trial, the researchers compared long-term survival between those who received kidney transplants and those who remained on dialysis.
“TTE allowed us to eliminate many of the biases that have clouded older registry studies and get as close as ethically possible to a randomised clinical trial,” explained lead author Dr Rachel Hellemans.
“We found that transplantation with standard-criteria kidneys still offers a clear survival benefit at virtually every age, but in the oldest, most comorbid recipients receiving lower-quality organs, that edge can all but disappear.”
The data showed a consistent survival advantage with standard-criteria donor kidneys – those from donors under 60 without significant risk factors for poor kidney function – regardless of recipient age or underlying health conditions.
However, the picture is less clear with expanded-criteria donor (ECD) kidneys, including organs from older donors or those with risk factors that may affect kidney quality.
Among patients aged 75 and older, five-year survival rates were around 57to 58 per cent, only slightly higher than the 54 per cent seen in patients who remained on dialysis. This was particularly the case for those with cardiovascular disease or those receiving kidneys from donors after circulatory death.
A key factor behind these findings is the higher early post-transplant mortality observed in high-risk patients.
The director of the ERA Registry, Dr. Vianda Stel said: “The breadth of data we could access via the ERA Registry showed that the survival advantage of a transplant plateaus for the very oldest or highest-risk patients who are likely to receive an expanded-criteria or circulatory-death donor kidney.
“This arms clinicians with guidance to have informed discussions with their patients. The message isn’t ‘don’t transplant older people.’ It’s ‘be open about uncertainty when the numbers say benefit may be marginal.”