In a recent study published in the journal Cell, researchers looked at the association between human longevity and growth and metabolic pathways.
There has been a lot of research on the relationship between nutrients and cellular responses in humans. However, there is a need for extensive research to determine the amount, types, and combinations of nutrients that can promote healthy longevity.
The researchers explored the impact of specific nutrients on the response pathways responsible for regulating disease and aging in humans.
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The protein-endocrine axis
Diets that include increased levels of protein and amino acids, such as methionine, were most effective in improving growth hormone (GH) signaling, as well as insulin-like growth factor 1 (IGF-) levels. 1). This, in turn, reduced rodent shelf life by stimulating a pro-aging axis, including increasing circulating IGF-1 levels. In particular, IGF-1 levels in individuals consuming high-protein diets than those reporting low-protein diets. In addition, mutations in the GH and GH receptor that reduced growth gene levels resulted in an extended shelf life of 35% to 40%.
In particular, deficiencies in both GH and GH receptors (GHR) reduced circulating IGF-1 levels, which served as the main promoter of growth in humans. This sharp drop and reduced insulin levels due to decreased GHR levels could lead to a reduction in GHR signaling, which in turn translates into prolonged longevity. Notably, compared to wild-type mice, mice that had a smaller copy of the IGF-1R gene lived between 16% and 33% longer, while mice with mutations in the receptor substrate. of insulin 1 (IRS-1) also lived 16% to 30% more.
In addition, mutations found in the target kinase of rapamycin S6 (TOR-S6K) or GH-IGF-1 resulted in increased longevity and health. In addition, individuals with mutations in the GHR gene showed protection against age-related diseases. In particular, the incidence of cancer in Ecuadorian individuals with GHR deficiency was remarkably low. In addition, these individuals also reported a low incidence of diabetes despite the high prevalence of diabetes in this population, probably due to increased insulin sensitivity in people.
The sugar-endocrine axis
Sugars have also been found to play a critical role in signaling, leading to the acceleration of the aging process. The team noted that the disruption of adenylyl cyclase (AC) type 5, which is seen mainly in the brain and heart, caused a 30% increase in half-life and reduced the incidence of cardiomyopathy in mice. . In addition, disruption of the RIIb subunit of protein kinase A (PKA) in male mice was associated with increased longevity, lower fasting glucose and insulin levels, and a lower incidence of left ventricular hypertrophy.
Caloric restriction (CR) in humans
CR resulted in a reduction in total body weight and loss of adiposity, which resulted in higher fat-free mass levels in proportion to total body mass in individuals who were on a CR regimen. Associations were also found between CR and increased insulin sensitivity, lower risk of cardiovascular disease, and improved liver health. In addition, this indicated a delay in aging, which was verified by the methylation clock.
The team noted that crucial processes for the transition to a healthier state included autophagy, proteostasis, involvement of gene regulatory mechanisms, including ribonucleic acid (RNA) processing, and alterations in signaling. of growth, including translation and synthetic pathways, and energy metabolism and the switch to lipid fuel. use. This indicated that longevity depended on reduced activity in the growth pathways and a change in metabolic processes associated with fasting conditions.
In addition, the team studied the health benefits of fasting, along with determining how each type of fasting affects health, disease risk factors, and longevity.
The regimen used in the studies included a time-restricted diet (TRE), with a daily feeding window of eight to 10 hours each day, lasting between four and 12 weeks, and TRE imposed on five or more days a week. Almost all studies reported a reduction in weight and adiposity or waist circumference among individuals imposed by TRE. Improvements in factors associated with cardiovascular disease were also reported. TREs with a six-hour feeding period were also effective in increasing insulin sensitivity.
Several studies have also reported the association of longer daily fasting periods involving skipping breakfast with higher mortality rates. Another TRE mode that required participants to fast every two days improved cardiovascular markers, reduced trunk fat, improved fat-to-lean ratio, and improved b-hydroxybutyrate levels.
The diet of longevity
The team observed that a diet with low but sufficient levels of protein or normal levels of protein with a large amount of legume consumption, resulting in a lower intake of methionine and other amino acids, contributed to the reduction of pro-aging activity. GHR, insulin, IGF-1 and TOR-S6K signaling. However, for people 65 years of age and older, the low-protein diet showed no reduction in IGF-1 levels and instead resulted in loss of lean body mass.
Overall, the results of the study highlighted the importance of longevity diet in improving standard health care. Researchers believe that this diet could prevent morbidity and improve health into old age.
Nutrition, longevity and disease: from molecular mechanisms to interventions, Valter D. Longo, Rozalyn M. Anderson, Cell, VOLUME 185, NUMBER 9, P1455-1470, April 28, 2022, DOI: https://doi.org /10.1016 /j.cell.2022.04.002