Aging is an unavoidable biological process characterized by a gradual deterioration of structural integrity and physiological function, driven by complex and multifactorial mechanisms. This process is a major contributing factor to numerous chronic disorders, including skin aging, neurodegenerative diseases [1,2], cardiovascular diseases [3], metabolic syndrome [4], and cancer [5]. Among the various phenotypic features of aging, the skin provides a visible indication, often exhibiting wrinkles, dryness, roughness, discoloration, and reduced brightness.

Intrinsic skin aging is a primary contributor to overall skin aging and is mainly driven by telomere shortening, chronic inflammation, and oxidative stress induced by free radicals [6]. Telomeres are tandemly repeated DNA sequences (TTAGGG in vertebrates) positioned at the termini of linear chromosomes, where they interact with a complex of specific proteins to maintain genomic stability. In most somatic cells, telomeres progressively shorten with each cell division, and once a critical length is reached, cells enter a permanent growth-arrest state termed replicative senescence. Within the epidermis, the accumulation of senescent cells impairs barrier function, resulting in elevated trans-epidermal water loss (TEWL). In the dermis, senescent cells contribute to the degradation of extracellular matrix components, including a reduction in type III collagen, which promotes wrinkle formation [7]. Chronic, low-grade inflammation represents another hallmark of aging which is closely related to the incidence and mortality rates of the elderly. This phenomenon, known as inflammaging, is usually identified as elevated circulating levels of pro-inflammatory cytokines such as, IL-1β, IL-6, and TNF-α [8]. Additionally, oxidative stress plays a vital role in the aging process by inducing DNA damage and disrupting redox homeostasis, finally leading to cell cycle arrest and apoptosis [9].

Apoptosis is a fundamental mechanism through which organisms maintain tissue homeostasis and integrity. However, senescent cells exhibit a marked resistance to apoptotic signals [10]. These cells actively release a diverse array of cytokines, chemokines, proteolytic enzymes and growth factors—collectively called the senescence-associated secretory phenotypes (SASPs)—which modulate the surrounding microenvironment and trigger persistent inflammation and tissue deterioration by influencing nearby healthy cells [11,12]. Therefore, the selective elimination of senescent cells (senolytics) or the suppression of SASP production in these cells (senomorphics) represent two promising anti-aging therapeutic strategies.

Recent investigations have highlighted the anti-aging potential of marine-derived bioactive substances originating from algae, invertebrates, and vertebrates [[13], [14], [15]]. Among these compounds, fucoxanthin (Fx) — a well-known xanthophyll carotenoid abundant distributed in edible brown algae such as Laminaria japonica and Undaria pinnatifida, possesses a unique chemical structure characterized by allene bonds, a 5,6-monocyclic epoxide, acetylated groups, and multiple conjugated double bonds [16]. Fx exhibits potent antioxidant activity by activating the Nrf2/ARE signaling pathway [17], stabilization of mitochondrial membrane potential to counteract oxidative injury [18], and scavenging free radicals owing to its high degree of unsaturation [19]. Moreover, Fx exhibits pronounced anti-inflammatory properties by suppressing NF-κB pathway activation [20]. Given these properties, Fx has significant potential for mitigating chronic inflammation and oxidative stress associated with aging. Our previous studies showed that topical or oral administration of Fx can effectively protect the dorsal skin of hairless mice from ultraviolet (UV)-induced photoaging [21,22]. Furthermore, we detected two major metabolites of Fx, fucoxanthinol and amarouciaxanthin A -, in both the epidermis and dermis of mice fed a diet containing 0.001% Fx [21]. Additionally, astaxanthin, a carotenoid structurally similar to Fx, delays chronic skin aging in aged mice [23]. However, the effects of Fx on intrinsic skin aging in mice remain unknown. Although photoaging and intrinsic aging share common features such as oxidative stress and inflammation, their underlying mechanisms differ substantially. Photoaging is driven by intense oxidative and inflammatory responses, whereas intrinsic aging is associated with the gradual accumulation of free radicals, and chronic low-grade inflammation. Moreover, intrinsic aging is influenced by additional complex factors, including metabolic alterations, cellular senescence, telomere shortening, and immune system decline [24]. Therefore, the present study focused on the physiological effects of dietary Fx on natural aging, particularly focusing on skin health, in aged C57BL/6J mice. Meanwhile, intrinsic aging affects multiple organs beyond the skin, leading to metabolic dysregulation, chronic inflammation, and functional decline. Given that the metabolites of Fx is systemically distributed, its potential effects may not be limited to the skin but could extend to other tissues [25]. Accordingly, this study also evaluated aging-associated changes in selected tissues to provide a broader assessment of the physiological effects of dietary Fx.