Background: The positive effect of caloric restriction (CR) in the intervention of age-related skin and hair disorders is a disputed issue, and the mechanisms by which it influences the immune response in old age are still not well understood. This work postulated that CR could prevent age-related cutaneous disorders by enhancing skin immunogenicity and regenerative cells expression with downregulation of inflammatory, oxidative and apoptotic stressors.Methods: A total of 45 female Wister rats were divided into three groups; adult control, aged, and aged-CR groups. The CR group was subjected to caloric restriction from 13 to19 months of age. Dorsal skin samples were collected for each group and subjected to light and scanning microscopy, morphometric, biochemical, molecular and immunohistochemical studies. Results: In contrast to the devastating impact of aging on rat skin and hair, CR resulted in upregulations of both oxide synthase (iNOS) and CD4 gene immune cells expressions, p53, cytokeratin (CK) 19, and transforming growth factor-beta 2 (TGF-β2) immune expression levels. Additionally, we observed amelioration of both inflammatory and oxidative stress factors with preservation of most of skin and hair internal and external structures, collagen, and elastic fibers percentage area. Conclusion: These initial outcomes strongly suggest that in aged rat skin, the CR can protect against skin and hair aging through elevations of both innate and adaptive immunity. These effects were mediated through prohibition of the catabolic effects of apoptotic/oxidative and inflammatory stressors and promotion of the anabolic effects of stem and immune cells and will be explored in further studies.