An Epigenetic View of the Benefits of Calorie Restriction in Aged Rats
One way to look at the impact of aging versus the impact of an intervention to slow aging is to examine transcriptional changes in cells. Pick a tissue and cell type, assess the whole transcriptome of RNA molecules produced by that cell type, then compare old versus young animals and treated versus untreated old animals. Here, researchers compare the effects of aging in rat muscle versus the effects of calorie restriction, an intervention known to slow aging in mammals. As one might expect, calorie restriction reduces the magnitude of many of the changes in transcription that take place with age.
Age-related muscle wasting, sarcopenia is an extensive loss of muscle mass and strength with age and a major cause of disability and accidents in the elderly. Mechanisms purported to be involved in muscle ageing and sarcopenia are numerous but poorly understood, necessitating deeper study. Hence, we employed high-throughput RNA sequencing to survey the global changes in protein-coding gene expression occurring in skeletal muscle with age. Caloric restriction (CR) is a known prophylactic intervention against sarcopenia. Therefore, total RNA was isolated from the muscle tissue of both rats fed ad libitum and CR rats. RNA-seq data were subjected to Gene Ontology, pathway, co-expression, and interaction network analyses. This revealed the functional pathways most activated by both ageing and CR, as well as the key "hub" proteins involved in their activation.
RNA-seq revealed 442 protein-coding genes to be upregulated and 377 to be downregulated in aged muscle, compared to young muscle. Upregulated genes were commonly involved in protein folding and immune responses; meanwhile, downregulated genes were often related to developmental biology. CR was found to suppress 69.7% and rescue 57.8% of the genes found to be upregulated and downregulated in aged muscle, respectively. In addition, CR uniquely upregulated 291 and downregulated 304 protein-coding genes. This data may provide the initial evidence for several targets for potential future therapeutic interventions against sarcopenia.
In Jan Gruber's new paper where they evaluated mortality data created weights for a new mortality calculator LinAge2, BMI is protective of death in both genders. Higher BMI live longer.
I have thought for a while CR didn't work in humans, or that maybe at younger ages it gives benefit, but if you look at mortality from hospital stays or protein requirements in the elderly, it becomes obvious CR is harmful.
@Lee A confounding factor with that though would be the fact that people tend to lose weight when they are sick. So if you're lumping together people who have lower weight from sickness with those who have a lower weight from CR, without considering the reason for the lower weight, then even if CR is beneficial that benefit will be swamped out in the data by all the people who have lost weight from illness.