In the protein nutrition strategy of middle-aged and elderly people, some believe that low protein is good for health, while others believe high protein is good for health. Facing the contradictory situation, the following hypothesis is proposed. There is a process of change from lower to higher ratio of protein nutritional requirements that are good for health in the human body after about 50 years of age, and the age at which the switch occurs is around 65 years of age. Hence, in this study, 50, 25-month-old male rats were randomly divided into five groups: Control (basal diet), LP (low-protein diet with a 30% decrease in protein content compared to the basal diet), HP (high-protein diet with a 30% increase in protein content compared to the basal diet), Model 1 (switched from LP to HP feed at week 4), and Model 2 (switched from LP to HP feed at week 7). After a total of 10 weeks intervention, the liver and serum samples were examined for aging-related indicators, and a newly comprehensive quantitative score was generated using principal component analysis (PCA). The effects of the five protein nutritional modalities were quantified in descending order: Model 1 > HP > LP > Control > Model 2. Furthermore, the differential metabolites in serum and feces were determined by orthogonal partial least squares discriminant analysis, and 15 differential metabolites, significantly associated with protein intake, were identified by Spearman’s correlation analysis (p < 0.05). Among the fecal metabolites, 10 were positively correlated and 3 were negatively correlated. In the serum, tyrosine and lactate levels were positively correlated, and acetate levels were negatively correlated. MetaboAnalyst analysis identified that the metabolic pathways influenced by protein intake were mainly related to amino acid and carbohydrate metabolism. The results of metabolomic analysis elucidate the mechanisms underlying the preceding effects to some degree. These efforts not only contribute to a unified protein nutrition strategy but also positively impact the building of a wiser approach to protein nutrition, thereby helping middle-aged and older populations achieve healthy aging.

IntroductionRecent evidence supports a role for the gut microbe-metabolites in longevity. However, the phenomenon of hypertension is more common in the longevity area and whether hypertension is associated with longevity remains unclear. Here, we hypothesize that the levels of gut microbiota, SCFAs, and urine metabolites were different between hypertension elderly and hypertension longevity.MethodsWe recruited 46 elderly volunteers from Donglan County, Guangxi, and 32 were selected and included in the experiment. The subjects with hypertension were divided into two groups according to age, Hypertension Elderly (HTE, aged 70.5 ± 8.59, n = 19) and Hypertension Longevity (HTL, aged 100 ± 5.72, n = 13). The gut microbiota, SCFAs, and urine metabolites were determined by three-generation 16S rRNA full-length sequencing, GC-MS, and 1H-NMR, respectively.ResultsCompared with the HTL group, the HTE group had higher levels of hypertension-related genera Klebsiella and Streptococcus, while having lower levels of the SCFA-producing genera Bacteroides, Faecalibacterium, and Alistipes. Based on LEFse analysis, Klebsiella pneumoniae, Lactobacillus gasseri, Streptococcus salivarius, Ruminococcus, Actinomyces, Rikenellaceae, f_Saccharimonadaceae, Clostridium perfringens, and Bacteroids, Faecalibacterium prausnitzii, Parabacteroides, Alistipes were biomarkers that showed significant differences between the groups. In addition, the microbial pathways associated with K. pneumoniae and E. coli may promote hypertension, while A. muciniphila may play a role in reversing the development of hypertension in long-lived elderly. Metabolomics revealed that HTL contained a lower concentration of fecal acetate and propionate than HTE, while it contained a higher concentration of serum acetate and urine acetate. Furthermore, their immune cells exhibited no significant changes in SCFAs receptors.ConclusionAlthough long-lived elderly have extremely high systolic blood pressure, their unique gut microbiota composition and efficient acetate absorption in the colon may offset the damages caused by hypertension and maintain healthy homeostasis.