The secret to healthy ageing may lie not within stem cells themselves, but in the fragile cellular “neighbourhoods” that support them. New research from Indian scientists suggests that the gradual breakdown of these supportive environments—rather than intrinsic failure of stem cells—could be a critical driver of age-related tissue decline. This opens fresh directions for ageing research and regenerative medicine.
In a study published in Stem Cell Reports, scientists from the Agharkar Research Institute (ARI), Pune, an autonomous institute under the Department of Science and Technology (DST), have shown that support cells surrounding stem cells are far more vulnerable to ageing-related damage. When these cells deteriorate, stem cells lose their ability to survive and regenerate tissue, even if they themselves remain largely intact.
As populations age globally, understanding how tissues lose their regenerative capacity has become a scientific priority. Stem cells are central to this process because they continuously renew tissues such as skin, intestine, muscle and reproductive organs. However, the new findings challenge the long-held assumption that ageing begins within stem cells themselves.
To investigate this, the ARI team studied the ovaries of the fruit fly Drosophila melanogaster, a powerful model organism widely used in ageing and developmental biology. The focus was on germline stem cells—specialised adult stem cells that continually divide to produce eggs—and the niche cells that surround and support them.
The researchers discovered a striking contrast in how different cell types handle autophagy, the cell’s internal recycling and repair system. Germline stem cells were able to function even with very low levels of autophagy. In contrast, neighbouring support cells known as cap cells were critically dependent on this process for their long-term survival.
When key autophagy-related genes, including Atg1, Atg5 and Atg9, were selectively switched off in cap cells, these niche cells began to accumulate cellular damage. Over time, they lost their structural integrity and failed to provide essential biochemical signals to the stem cells. As a result, germline stem cells were gradually lost—not because they were intrinsically weak, but because their supportive microenvironment collapsed.
“These findings show that ageing in this system starts with the support cells, not the stem cells,” the researchers note. Cap cells act like caretakers, supplying constant molecular cues, particularly Bone Morphogenetic Protein (BMP) signals, that help stem cells maintain their identity and continue producing eggs. When autophagy falters in midlife, BMP signalling weakens, and the stem cells can no longer be sustained.
The study reframes ageing as a collective, ecosystem-level process rather than a purely cell-autonomous one. It highlights how the health of stem cells is tightly linked to the wellbeing of neighbouring cells, much like residents depending on the stability of their neighbourhood.
Led by Kiran Suhas Nilangekar and Dr. Bhupendra V. Shravage of the Developmental Biology Group at ARI, the work places the institute at the forefront of research into how stem cell niches age. Importantly, it demonstrates that different cell types within the same tissue have very different resilience thresholds, with support cells acting as early “weak links” that may trigger tissue decline.
Although the research was conducted in fruit flies, its implications extend far beyond. Core pathways such as autophagy and stem cell niche signalling are highly conserved across species. Similar stem cell–niche relationships exist in mammalian tissues including the intestine, skin and muscle, suggesting that protecting support cells could help preserve regenerative capacity in ageing humans, noted the researchers.
Looking ahead, the ARI team plans to explore how different cell types balance resilience and vulnerability during ageing, and whether targeted modulation of autophagy in niche cells can slow the loss of regenerative potential.
