The practice of calorie restriction (also known as dietary restriction) improves health and slows aging. This occurs to a greater degree in short-lived species than in our own comparatively long-lived species, but nonetheless, the benefits are evident. Researchers here discuss the evidence for calorie restriction to be protective of kidney function, but for that protection to decline with age. This is an interesting perspective on calorie restriction, one that I haven't see much mentioned in the past. Very little of our biochemistry and function escapes aging, and we might expect near any measurable aspect of physiology and metabolism to become worse in older people. So why not also a reduction in the ability of our metabolism to respond favorably to a lower calorie intake?
Dietary restriction (DR) is believed to be one of the most promising approaches to extend life span of different animal species and to delay deleterious age-related physiological alterations and diseases. Among others, DR was shown to ameliorate acute kidney injury (AKI) and chronic kidney disease (CKD). However, to date, a comprehensive analysis of the mechanisms of the protective effect of DR specifically in kidney pathologies has not been carried out.
The protective properties of DR are mediated by a range of signaling pathways associated with adaptation to reduced nutrient intake. The adaptation is accompanied by a number of metabolic changes, such as autophagy activation, metabolic shifts toward lipid utilization and ketone bodies production, improvement of mitochondria functioning, and decreased oxidative stress. However, some studies indicated that with age, the gain of DR-mediated positive remodeling gradually decreases. This may be an obstacle if we seek to translate the DR approach into a clinic for the treatment of kidney diseases as most patients with AKI and CKD are elderly.
It is well known that aging is accompanied by impairments in a huge variety of organs and systems, such as hormonal regulation, stress sensing, autophagy and proteasomal activity, gene expression, and epigenome profile, increased damage to macromolecules and organelles including mitochondria. All these age-associated changes might be the reasons for the reduced protective potential of the DR during aging. Here we summarize the available mechanisms of DR-mediated nephroprotection and describe ways to improve the effectiveness of this approach for an aged kidney.