Abstract
Global average life expectancy continues to rise. As aging increases the likelihood of frailty, which encompasses metabolic, musculoskeletal, and cognitive deficits, there is a need for effective anti-aging treatments. It is well established in model organisms that dietary restriction (DR), such as caloric restriction or protein restriction, enhances health and lifespan. However, DR is not widely implemented in the clinic due to patient compliance and its lack of mechanistic underpinnings. Thus, the present study tested the effects of a somewhat more clinically applicable and adoptable DR regimen, every-other-day (EOD) intermittent fasting, on frailty in 20-month-old male and female C57BL/6 mice. Frailty was determined by a series of metabolic, musculoskeletal, and cognitive tasks performed prior to and toward the end of the 2.5-month dietary intervention. Late-life EOD fasting attenuated overall energy intake, hypothalamic inflammatory gene expression, and frailty in males. However, it failed to reduce overall caloric intake and had a little positive effect in females. Given that the selected benefits of DR are dependent on augmented production of the gasotransmitter hydrogen sulfide (H2S) and that renal H2S production declines with age, we tested the effects of EOD fasting on renal H2S production capacity and its connection to frailty in males. EOD fasting boosted renal H2S production, which positively correlated with improvements in multiple components of frailty tasks. Therefore, late-life initiated EOD fasting is sufficient to reduce aging-related frailty, at least in males, and suggests that renal H2S production capacity may modulate the effects of late-life EOD fasting on frailty.
Highlights
The global population over age 65 is expected to nearly double from 8.5 to 16.7% by the year 2050 [1], largely due to advancements in medicine and paradigm shifts in public health policies
Late-life initiated EOD fasting is sufficient to reduce aging-related frailty, at least in males, and suggests that renal H2S production capacity may modulate the systemic effects of late-life EOD fasting on frailty
Mice that remained on the ad libitum (AL) feeding regimen (Chow AL) consumed more food overall than the mice placed on the EOD fasting regimen (Chow EOD)
Summary
The global population over age 65 is expected to nearly double from 8.5 to 16.7% by the year 2050 [1], largely due to advancements in medicine and paradigm shifts in public health policies. Studies that compared the effects of EOD fasting and continuous CR in adult mice showed that both dietary regimens are comparably effective to enhance glucose metabolism/insulin sensitivity [75] and to protect against aging-related neurobehavioral deficits (i.e., decreased locomotion and memory impairments; [76]). These findings suggest EOD fasting initiated in late-life may enhance health and lifespan, at least in rodents. Late-life initiated EOD fasting is sufficient to reduce aging-related frailty, at least in males, and suggests that renal H2S production capacity may modulate the systemic effects of late-life EOD fasting on frailty
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