Taking out the trash is a chore even our cells cannot avoid. Through a process called autophagy, cells collect damaged proteins and other waste, break them down and reuse their molecular building blocks. This cellular recycling system helps prevent the accumulation of debris that can damage cells and contribute to disease.

For years, scientists have generally believed that autophagy declines as people grow older. That decline has been considered one of the hallmarks of ageing and has been linked to cancer, cardiovascular disease, diabetes and neurodegenerative conditions. But new research suggests the story is considerably more complicated.

Scientists at Sanford Burnham Prebys Medical Discovery Institute reported in Aging Cell that autophagy does not simply slow down across the body with age. Instead, its activity appears to change differently depending on the type of cell and a person’s sex. The researchers also found preliminary evidence that exercise could influence cellular recycling in older adults.

“We commonly see people cite this idea that autophagy declines with age, but the actual evidence for this in humans is very thin,” said senior author Caroline Kumsta, PhD, an assistant professor at Sanford Burnham Prebys. To investigate, researchers studied skin and blood samples from healthy volunteers aged 23 to 72 and transformed some skin cells into induced neurons, allowing them to examine several cell types.

The team analysed the activity of genes involved in autophagy and directly measured how quickly cells recycled their contents. The results revealed striking differences. Autophagy declined with age in male skin cells but remained stable in female skin cells. In female-induced neurons, it actually increased with age. Gene activity also did not reliably predict the amount of recycling taking place inside cells.

The researchers then examined whether autophagy was related to physical health. Among adults aged 70 and older, higher autophagy was associated with poorer physical function across the cell types studied. Greater autophagy in blood cells was linked to lower aerobic fitness, while higher levels in skin cells were associated with higher body mass index. In induced neurons, greater autophagy was associated with lower grip strength and metabolism and a higher resting heart rate.

The findings raise the intriguing possibility that more cellular recycling is not necessarily better at every age. “It appears that increased autophagy flux may be good in younger people yet problematic in older people,” Kumsta said. Lead author Tatiana Moreno, PhD, said the results show that researchers need to consider cell type, sex and age when exploring autophagy as a possible target for healthy-ageing treatments.

A small pilot experiment also offered a clue about the role of exercise. Five adults aged 77 to 88 completed a 12-week mild exercise programme designed to help prevent falls. Afterwards, their blood-cell autophagy appeared to move towards levels seen in younger people while their physical performance improved. Although the pilot was far too small to establish cause and effect, the researchers say it provides an intriguing direction for future studies — and another sign that the relationship between ageing and cellular recycling may be far more dynamic than previously thought.

More information: Tatiana Moreno et al, Autophagy Flux Is Remodeled Sex- and Cell Type-Specifically During Human Aging, and Is Linked to Reduced Physical Function in Older Adults, Aging Cell. DOI: 10.1111/acel.70734

Journal information: Aging Cell Provided by Sanford Burnham Prebys