Research round-up: Ageing

Low self-confidence leads to greater frailty

Many people accept frailty as a natural effect of ageing, but a study by researchers at Johns Hopkins University in Baltimore, Maryland, suggests that maybe they shouldn’t. It found that the older adults most likely to become physically weak and vulnerable were those who lacked ‘self-efficacy’, a term used to describe confidence in one’s ability to meet life’s challenges.

The team studied more than 4,800 participants in the US National Health and Aging Trends Study, which began in 2011 and monitors the well-being of people aged 65 and older who still live in the community, rather than in hospitals or nursing homes. The researchers assessed people’s self-efficacy by noting how much they agreed with the statement: “When I really want to do something, I usually find a way to do it.” They then tracked participants’ levels of frailty over time, based on criteria such as how often they felt exhausted, whether they had unintended weight loss, and whether their walking speed was low for their age.

When people initially scored low in self-efficacy, their risk of becoming frail during the seven-year study was about 41% higher than that of their more confident peers. This increased risk persisted in participants of different ages, backgrounds and levels of education. The researchers suggest exploring measures to boost older adults’ self-confidence, such as teaching exercise routines and the principles of good nutrition, to see whether they help ward off frailty and its attendant health effects.

J. Am. Geriatr. Soc. 69, 3507–3518 (2021)

Microbes reverse signs of mouse ageing

Throughout our lives, microorganisms move in and out of our guts like short-term tenants — and manipulating their comings and goings could potentially nudge the ageing process into reverse. When researchers from University College Cork in Ireland fortified the gut microbiomes of old mice with bacteria from younger ones, it improved the old mice’s immunity and cognitive function.

Part of Nature Outlook: Ageing

In previous studies, shunting gut microbes from young fish into middle-aged ones seemed to increase the older fishes’ lifespan, and the Cork team wondered whether they could produce similar effects in mice. To test this, they transplanted fecal microbes from young mice (3–4 months old) into older ones (19–20 months) and observed the effects for four weeks.

The microbes were like a fountain of youth. The mice that received them had greater immunity than before the transplant and achieved higher scores in cognitive tests than mice in the comparison group, including on a ‘water maze’ test in which they needed to find a submerged, hidden platform. The team also saw changes in the brains’ hippocampus that suggested ageing reversal, such as the production of N-glycolylneuraminate and other chemicals that aid cognition.

Nature Aging 1, 666–676 (2021)

Exercise more for a happier old age

Across the board, doctors promote exercise to increase well-being in people of all ages. But new data suggest that these benefits may be especially pronounced in the elderly.

The researchers, from universities and hospitals in the United Kingdom and Spain, took their data from a sample of 14,585 people aged over 65 in six low- and middle-income countries in the World Health Organization’s Study on Global Ageing and Adult Health (SAGE). In the original SAGE study, participants were asked to rate their happiness regularly over a three-year period, choosing from a range of five options from ‘very unhappy’ to ‘very happy’. SAGE administrators also recorded whether or not each participant had met the recommended guidelines of at least 150 minutes of moderate exercise per week, which could include activities such as brisk walking, cycling or playing tennis.

The UK and Spanish team reported in their new analysis that the higher people scored in measures of physical activity, the happier they felt over time. Among people who regularly met the exercise guidelines, more than half reported feeling either happy or very happy, whereas among those who did not meet the guidelines, only 15% described themselves that positively.

Several factors have been proposed to explain the association between exercise and happiness in older people, although the researchers acknowledge that factors including limited mobility, lack of sleep and anxiety can affect an older person’s ability to exercise.

Previous studies have shown that exercise triggers the release of endorphins, which promote a sense of well-being. Exercise also elicits calm-inducing brain chemicals such as gamma-aminobutyric acid (GABA) and endocannabinoids, helping to relieve anxiety. Finally, active people are less likely to succumb to cognitive decline as they age.

Age Ageing 50, 488–497 (2021)

Social isolation linked to disability problems

Not only are lonely older adults less happy than their more gregarious peers, but they also struggle more with disability and functioning after hospital discharge, according to a study of 997 older people with serious illness.

All the participants were part of the US National Health and Aging Trends Study and had been admitted to a hospital intensive-care unit at some point during a six-year period from 2011 to 2017. Researchers at Yale School of Medicine in New Haven, Connecticut, and the University of Maryland School of Medicine in Baltimore assessed social isolation by looking at factors such as how connected people felt to their family, friends and partners.

The team’s analysis showed that the more socially isolated people were, the more they struggled with disabilities after hospital discharge, and the more likely they were to die within a year of being admitted to hospital. For each one-point increase in a participant’s score on the study’s social-isolation scale, which ranged from 0 to 6, they could expect a 7% greater disability burden and a 14% higher mortality risk in the year after their hospital admission.

The results underscore the importance of screening older people for social isolation — perhaps around the time of their hospital visit — so clinicians can recommend some steps to keep them engaged in the community, the researchers say. Such a strategy could lower people’s risk of physical deterioration or death during the vulnerable post-discharge period, the researchers conclude.

JAMA Intern. Med. 181, 1433–1439 (2021)

How ageing changes gene expression

For years, physicians’ clearest vantage point on ageing was how it appeared to the naked eye, but a research team at the Salk Institute for Biological Studies in La Jolla, California, has provided a much clearer view. It has created a comprehensive model of the human transcriptome that documents thousands of ways in which the ageing process changes the way genes function.

To illustrate the full spectrum of ageing-related gene expression, the team collected more than 3,000 high-quality RNA samples from people of varying ages with a variety of medical histories and backgrounds. The RNA came from a wide range of body tissues including the brain, heart, skin, retina and bones.

The researchers then assessed patterns of ageing-related gene function by pinpointing groups of genes that functioned differently in people of different ages. They sought to uncover how these gene processes were involved in ageing. For example, they found that some genes that control apoptosis (a type of cell death) in the brain functioned differently in older people than in younger ones. The model also serves as what the researchers call an ultra-predictive RNA ageing clock, meaning that if they take a sample of someone’s RNA and compare it against their accumulated library of RNA data, they can determine how old that person is with a high degree of accuracy.

The team hopes their model can serve as a reference point for testing anti-ageing therapies in humans. Over the course of a clinical trial, a researcher could check whether a drug shifts the gene expression patterns towards those normally seen in younger people — in effect, turning back the RNA-ageing clock. Age-related changes in gene function could also serve as therapeutic targets for future drugs that promote healthy ageing.

Aging Cell 20, e13280 (2021)

Sex differences in Alzheimer’s disease

It has long been known that Alzheimer’s disease often manifests differently in women and men. Now, researchers at the University of California, San Francisco, and elsewhere have discovered some reasons why. Sex-based differences in X-chromosome function, they report, can affect symptoms of Alzheimer’s, such as difficulty accessing memories, and can also affect physical changes, such as the build-up of tau protein in the brain.

More from Nature Outlooks

The researchers examined more than 500 people after death, most of whom had been diagnosed with Alzheimer’s disease while they were alive. Autopsies paid particular attention to tissue from the dorsolateral prefrontal cortex, a brain region that governs attentional processes and working memory. The researchers extracted RNA from each tissue sample and sequenced it to get a clear picture of how genes on the X chromosome were functioning in each person’s brain.

In women, but not in men, high rates of expression of 19 different genes predicted slower cognitive decline, as measured in clinic-based neurological testing. By contrast, X-chromosome activity in men was more associated with physical brain changes. When men (but not women) had high expression of X-chromosome genes, they had more accumulation of tau protein, which forms structures known as neurofibrillary tangles that block communication between brain cells.

The researchers speculate that differences in the biology of X chromosomes — such as women having two X chromosomes, whereas men have just one — might contribute to the distinct ways in which Alzheimer’s disease develops in men and women. Continued studies of X chromosomes, they say, could further clarify these findings and suggest personalized treatments that alter X-chromosome activity.

JAMA Neurol. 78, 1249–1254 (2021)