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Mitigating Age-Associated Senescence in Subcutaneous Adipose Tissue through Caloric Restriction
Hamid Malekzadeh, Somaiah Chinnapaka, Zayaan Tirmizi, Asim Ejaz
Department of Plastic Surgery, University of Pittsburgh Medical Center
2024-01-15
Presenter: Hamid Malekzadeh
Affidavit:
I certify that the material proposed for presentation in this abstract has not been published in any scientific journal or previously presented at a major meeting.
Director Name: J. Peter Rubin
Author Category: Fellow Plastic Surgery
Presentation Category: Basic Science Research
Abstract Category: Aesthetics
Introduction:
Adipose tissue plays a key role in maintaining aesthetic contour of the body, but aging disrupts this balance, resulting in altered fat distribution. This includes a decline in subcutaneous adipose depots and an increase in insulin-resistant visceral adipose depots. Adipose-derived stem cells (ASCs) are essential components for tissue regeneration, yet aging adversely affects their stemness and regenerative potential.
Methods:
Stromal vascular fraction (SVF) was isolated from young (2 months) and aged (22-24 months) C57BL/6 mice. SVF cells were seeded and the 3rd passage of their culture was utilized for this study. Mitochondrial activity, expression of senescence markers, and autophagy in adipose-derived stem cells from young and aged mice were compared.
Results:
We observed age-related decreases in subcutaneous adipose tissue mass and increases in visceral fat depots. Aged subcutaneous ASCs showed heightened reactive oxygen species (ROS) production. Assessing mitochondrial membrane activity as an indicator of stem cell quiescence and senescence, we noted a significant decline in quiescent ASCs with age, specifically in subcutaneous adipose depots. Additionally, aged subcutaneous adipose tissue accumulated more senescent ASCs with impaired autophagy. However, long-term caloric restriction reduced mitochondrial activity in ASCs, preventing the accumulation of senescent cells and preserving autophagy activity in aging ASCs.
Discussion:
These findings suggest that caloric restriction and mimetics might offer a potential strategy to rejuvenate the stemness of aged ASCs. Further research, including controlled interventions in animals and human studies, would validate these findings and establish the clinical potential of this approach for enhancing the stemness of aged stem cells.
