Pune: Scientists at the Agharkar Research Institute in Pune reported that damage to stem cell support cells, not stem cells themselves, triggered age-related tissue decline, opening new directions for healthy ageing research.
According to the study, researchers found that the microenvironment surrounding stem cells played a decisive role in maintaining tissue health over time. The findings showed that neighbouring support cells were far more vulnerable to ageing-related damage than the stem cells they sustained.
The research team studied ovarian tissue in the fruit fly Drosophila melanogaster. The institute functions under the Department of Science and Technology. The study appeared as a cover article in the journal Stem Cell Reports.
Scientists observed that germline stem cells could survive with very low levels of autophagy. However, nearby support cells known as cap cells relied heavily on this internal recycling process for long-term survival.
When researchers switched off autophagy-related genes such as Atg1, Atg5, and Atg9 in cap cells, the cells accumulated damage. They gradually lost structure and stopped sending essential maintenance signals to stem cells. As a result, stem cells disappeared despite remaining intrinsically robust.
Healthy ageing research links autophagy failure to tissue decline
The study showed that ageing began with the breakdown of support cells rather than stem cells. Cap cells normally supply biochemical signals, including Bone Morphogenetic Protein signals, which preserve stem cell identity and egg production.
When autophagy weakened in these niche cells during midlife, BMP signalling also declined. Consequently, stem cells could no longer sustain themselves, directly linking microenvironmental damage to reduced regenerative capacity.
Researchers said the findings challenged the long-held belief that ageing mainly resulted from damage inside individual cells. Instead, the study highlighted ageing as a community-level process within tissues.
The team demonstrated that different cell types within the same tissue had distinct autophagy requirements. This insight underscored the need to study entire cellular ecosystems while designing strategies to delay ageing.
The study was led by Kiran Suhas Nilangekar and Dr Bhupendra V. Shravage at the Developmental Biology Group, ARI Pune. Researchers said the findings positioned the institute at the forefront of stem cell ageing research.
Although conducted in fruit flies, the pathways studied are conserved across species. Scientists said the results could inform future studies on mammalian tissues such as skin, intestine, and muscle.
Researchers added that strengthening or protecting support cells could indirectly prolong stem cell function. They said future work would explore whether targeted autophagy modulation could slow age-related tissue decline.
