Document Type
Article
Publication Date
10-1-2025
Original Citation
Mauduit O,
Kumar P,
Scholand K,
Aksan E,
Schaefer L,
Abu-Romman A,
Delcroix V,
Yu Z,
Sindikubwabo A,
Korstanje R,
Makarenkova H,
de Paiva C.
Exploring the transformative effects of calorie restriction on the lacrimal gland in adult mice. Geroscience. 2025;47(5):6157–76.
Keywords
JMG, Animals, Caloric Restriction, Lacrimal Apparatus, Mice, Mice, Inbred C57BL, Female, Dry Eye Syndromes, Aging, Cornea, Disease Models, Animal
JAX Source
Geroscience. 2025;47(5):6157–76.
ISSN
2509-2723
PMID
40580246
DOI
https://doi.org/10.1007/s11357-025-01748-w
Grant
The Jackson Laboratory Nathan Shock Center of Excellence in the Basic Biology of Aging AG038070 (RK)
Abstract
Advanced age is one of the most recognizable risk factors for dry eye. Dry eye disease affects millions worldwide and can result from age-related lacrimal gland dysfunction, which correlates with a decline in lacrimal gland secretory cell function and chronic inflammation. This study investigated the potential of calorie restriction to maintain lacrimal gland and ocular surface health. Adult female C57BL/6 J mice were subjected to a 40% calorie restriction for 4 months, starting at 6-7 months and continuing until 10-11 months. These mice were compared to controls fed ad libitum. Bulk RNA sequencing of lacrimal glands, conjunctiva, and cornea subjected to calorie restriction compared to ad libitum revealed significant differentially expressed genes (DEGs). Pathways enriched in the upregulated DEGs indicate enhanced circadian rhythm, secretory functions, and lipid metabolism. These findings were confirmed using individual qRT-PCR and western blotting. In contrast, pathways enriched in the downregulated DEGs were associated with immune cell activation, adaptive immune responses, extracellular matrix remodeling, and metalloproteinase activity. Histological sections of calorie-restricted lacrimal glands revealed reduced mononuclear cell infiltration and fewer positive cells for CD4, CD19, and MHC II than in ad libitum lacrimal glands. Calorie restriction also prevented age-related corneal barrier dysfunction and mitigated age-related conjunctival goblet cell loss, hallmarks of dry eye disease. These findings suggest that calorie restriction supports lacrimal gland and ocular surface health by reducing inflammation and extracellular matrix remodeling and by enhancing the lacrimal gland's secretory function.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.