In a new study released in Cell researchers looked at the relationship between longevity in humans to metabolic processes and growth.

There is a great deal of research on the relationship between cellular and nutritional responses in humans. However, there is the need for a thorough study to identify the amount of nutrients, the types, and combinations of nutrients that will aid in promoting healthy longevity.

Researchers studied the effect of specific nutrients on the response pathways that regulate diseases and the process of aging in humans.

Study of longevity, nutrition and diseases from molecular mechanisms to interventions. Image Credit: udra11 / Shutterstock

The protein-endocrine Axis

A diet that increased amino acid and protein levels, including methionine, proved to be the most effective in boosting the growth hormone (GH) signaling and insulin-like growth factor 1 (IGF-1) levels. This in turn decreased the life span of rodents through activating a pro-aging axis and also increasing IGF-1 levels in the bloodstream. Particularly IGF-1 levels were higher in those who consume high protein diets are higher than those who eat low-protein diets. Furthermore, changes in GH and GH receptors that decreased the growth gene’s levels resulted in prolonged lifespans of 35% to 40%..

Aside from that, the deficiency from the two GH as well as GH receptors (GHR) diminished the levels of IGF-1 in the bloodstream. IGF-1 which was the primary promoter of human growth. The dramatic decline in IGF-1 levels and lower levels of insulin caused by lower levels of GHR could result in a decrease in the activity of GHR, which will result in an extension of life. Incredibly, it was observed that, in comparison to wild-type mice, those with one less version of IGF-1R live 16%-33 percent longer, whereas mice that had Iris receptor substrate 1 (IRS-1) mutations also lived from 16% to 30 percentage more.

Additionally, mutations in either target-of rapamycin S6 Kinase (TOR-S6K) or GH-IGF-1 lead to a longer health and longevity. In addition, those who had genetic mutations within the GHR gene showed protection from the effects of age on diseases. In particular, the rate of cancer among Ecuadorian people suffering from GHR deficiency was extremely low. Additionally, these people have also reported a low prevalence of diabetes, despite the rate of diabetes among this group, possibly because of the increased insulin sensitivity of those.

The sugar-endocrine linkage

Sugars are also believed to play an important function in the process of signaling, resulting in the rapid aging process. The researchers found that deficiency of adenylyl-cyclase (AC) kind 5, typically found in the heart and brain and the brain, resulted in an increase of 30% in the median lifespan and a decrease in the rate of cardiac myopathy among mice. In addition, the depletion in the protein kinase (PKA) RIIb subunit in male mice was linked to longer life span in addition to lower fasting glucose levels and insulin levels as well as lower rates of left hypertrophy of the ventricular wall.

Caloric limitation (CR) for humans

CR led to a reduction in body weight as well as decreased adiposity that resulted in fat-free mass increasing relative to total body weight of those who are on an CR regimen. There were also associations between CR and increased insulin sensitivity, less risk of developing cardiovascular diseases, and better liver health. Additionally, this suggested the slowing of aging that was confirmed by the clock for methylation.

The research team found that the essential processes for achieving better health included proteostasis and autophagy. involvement of genes’ regulators, including ribonucleic acid (RNA) processing changes in growth signaling , including synthetic and translation pathways, and energy metabolism as well as the shift to the use of lipids as fuel. It was evident that longevity was linked to the decrease in the activities of the growth pathways as well as changes in metabolic processes that are associated with being fasted.


The team also studied the health benefits of fasting as well as the study of how each kind of fast impacts the health of people, diseases risk factors and the length of life.

The protocol utilized in the research included time-restricted diet (TRE) that included the daily window for eating between 8 and 10 hours per day, with a duration that ranges from four to 12 weeks as well as TRE applied to at least five days per week. Nearly all studies showed the reduction of the amount of weight and waist circumference in TRE-imposed people. Improved factors that are associated with cardiovascular diseases were also observed. The TREs that had a six-hour eating intervals were also efficient in increasing the sensitivity of insulin.

Numerous studies have also documented the link between prolonged intervals of fasting per day that do not include breakfast with higher mortality rates. Another method of TRE that requires participants to fast on a regular basis every day increased cardiovascular markers, decreased the amount of fat in the trunk, increased fat-to-lean ratios and enhanced levels of B-hydroxybutyrate.

The diet for longevity

The study team found that the diet that had moderate but adequate levels of protein or regular levels of protein, coupled with the highest quantity of legumes, leading to a lesser intake of methionine as well as various amino acids led to the decrease in the pro-aging activity of GHR IGF-1, insulin and TOR-S6K signaling. However, for those 65 and over the diet that was low in protein did not show any decrease in IGF-1 levels, but instead caused the loss of body fat.

The overall findings of the study pointed out the importance in the long-term diet to improve the standard of healthcare. Researchers believe that this type of diet can help prevent morbidity and enhance longevity into old age.

Journal reference:
  • Nutrition, longevity and disease: From molecular mechanisms to interventions, Valter D. Longo, Rozalyn M. Anderson, Cell, VOLUME 185, ISSUE 9, P1455-1470, APRIL 28, 2022, DOI:,