The Effect of Carbohydrate-Restricted Diets on the Skin Aging of Mice

Abstract

Low-carbohydrate, high-protein diets, known as carbohydrate-restricted diets, are in contrast to the carbohydrate-centric meals typical of the Japanese diet. Carbohydraterestricted diets were reported to reduce visceral fat, owing to which they have attracted attention and been widely implemented. If, as proposed, carbohydrate-restricted diets are effective in delaying senescence, then Japanese diets have a hidden potential to evolve further. However, long-term carbohydrate restriction in mice was reported to have a negative effect on the cardiovascular system, with shortening of lifespan due to activation of mechanistic target of rapamycin (mTOR). As a result, the safety of long-term adherence to carbohydraterestricted diets remains doubtful. Recently, we conducted a study using senescence-accelerated mouse-prone 8 (SAMP8) mice to examine the effects of a carbohydrate-restricted diet on aging and skin senescence, and to determine the effect of long-term carbohydrate restriction on the aging process in mice. Here, we discuss the safety of long-term carbohydrate restriction based on the findings obtained from animal studies.

Low-carbohydrate diets adversely impact the skin of a mouse model of photoaging exposed to ultraviolet B radiation

“…Thickening of the epidermis is one of the most prominent signs of photoaging, which is considered to be an extrinsic type of aging caused by UV rays and is a phenomenon not observed during endogenous aging. (11,14,17,18) Chronological skin aging causes the skin to atrophy and become thin, whereas photoaging causes the epidermis to become thicker as a defense mechanism to protect the basal cell layer and dermal layer from UV rays. UVB radiation generates reactive oxygen species (ROS) in the skin tissue, inducing the production of pro-inflammatory cytokines (TNF-α, IL-1β, etc.…”

“…(20) LC diets induce an increase in thiobarbituric acid reactive substances in the skin, promote chronic inflammation, and further suppress the autophagic activity associated with decreased mTOR activation. (11,24,25) Therefore, ROS produced in the skin may amplify the ROS migrated from the liver to worsen skin morphology. In addition, skin damage resulting from LC diet intake while being exposed to UVB radiation appears to occur as a result of an increase in pro-inflammatory cytokines as well as NF-κB and MMP activation, which may be directly induced by oxidative stress.…”

“…(6,7) Moreover, the administration of LC diets has also been reported to accelerate aging and cause heart disease, hence raising questions about their safety. (8)(9)(10)(11)(12) In recent years, many media outlets have promoted LC diets for the maintenance of good health (i.e., to prevent aging and obesity), causing a subsequent increase in the number of people following these diets, even among nonobese individuals. Meanwhile, a decrease in dietary carbohydrate levels has been found to be accompanied by an increase in dietary fat and protein levels.…”

“…The skin, considered to be the largest organ in humans, functions as a sensor for exogenous stimuli, undergoing dynamic changes in response to internal and external environmental changes. (13)(14)(15) Okouchi et al (11) reported that LC diets aggravate skin aging in SAMP8 mice, a model of accelerated aging. Meanwhile, photoaging, which is distinct from chronological aging, is defined as deterioration of the skin morphology as a result of ultraviolet (UV) radiation.…”

Modulation of CT1 Function: From Klotho Protein to Ammonia and Beyond

“…Whether mTOR cross talks with SGK1 in the regulation of CT1 remains currently unknown, yet both kinases might participate in the adjustment of cellular creatine content to nutrient and energy supply ( 21 ). For instance, mTOR can be activated by various amino acids ( 22 ), time-of-day-dependent caloric restriction ( 23 ), or carbohydrate-restricted feeding ( 24 ), with diet-driven mTOR activation potentially followed by creatine stream via CT1.…”