Caloric restriction attenuates age-related liver and kidney alterations in mice: Histological evidence

This study evaluated the histological impact of long-term caloric restriction (CR) on liver and kidney aging, assessing fibrosis, metabolic overload, and senescence-associated readouts.

Eight-week-old male C57BL/6 mice were assigned to a standard diet (SD) or 50% CR and sacrificed at 12 or 16 months. A two-month-old group served as control (n=5/group). Liver and kidney tissues were processed for Hematoxylin and Eosin (H&E), Periodic Acid-Schiff (PAS), and Masson's Trichrome staining. Immunohistochemistry (IHC) assessed SIRT1, p16^INK4a, and acetylated p53 (Lys382) in both organs, and β-galactosidase immunoreactivity (IHC-DAB) in liver. Sections underwent morphometric quantification and statistical analysis.

Aged SD mice exhibited liver injury, increased PAS positivity, and collagen deposition, whereas CR attenuated these changes. The SD 16M group displayed the highest PAS positivity, while CR limited glycogen accumulation and preserved lobular architecture. In the kidney, SD animals developed tubular degeneration and architectural disruption; CR preserved renal structure and reduced tubular damage. CR was associated with higher SIRT1 immunoreactivity and lower acetylated p53, consistent with preserved SIRT1-linked deacetylation status. p16-positive cells increased with age under SD and were reduced by CR, though not fully normalized at 16 months. β-galactosidase immunoreactivity was evident in aged SD hepatocytes but minimal in CR groups.

Long-term CR preserves hepatic and renal histoarchitecture during aging by limiting metabolic overload, fibrotic remodeling, and senescence, accompanied by a sustained SIRT1/acetyl-p53 profile consistent with reduced p53 activation.