How can life be longer? New advances!

Dietary restriction, including intermittent fasting, is often thought to improve health. Multiple studies have shown that fasting extends the lifespan of a wide range of experimental organisms. Many prospective clinical trials have also shown that fasting reduces risk factors for diseases associated with aging, including cardiovascular disease, diabetes, and cancer. Fasting also increases resistance to various oxidative stresses, such as acute surgical stress. There are even studies showing that fasting enhances cancer treatment.

However, it is not clear whether different types of dietary restrictions extend life expectancy in the same way because the mechanisms that extend life expectancy are complex and unresolved. If the specific nutrient components of dietary restriction that are associated with life extension can be identified, a more targeted and feasible dietary restriction strategy can be defined.

On February 2, 2024, Monash University researchers published a research paper in the journal GeroScience entitled "Short-term fasting of a single amino acid extends lifespan".

The team found that intermittent, short-term deprivation of the essential amino acid isoleucine in the diet (i.e., dietary deficiency of isoleucine) in the model organism D. melanogaster significantly improves its resistance to stress and extends its lifespan, opening up new ways of understanding the impact of diet on longevity and health.

The study identifies a simpler alternative to traditional intermittent fasting, offering new possibilities for extending lifespans and promoting healthy aging.

Unlike traditional intermittent fasting, this approach does not require a significant reduction in overall food intake, making it a more practical and feasible strategy. This study not only expands our understanding of the impact of diet on longevity but also has the potential to revolutionize our understanding of how diet can help with longevity.

Previous research has shown that moderate restriction of all dietary amino acids can lead to stress resistance, but to increase longevity, it needs to be maintained over a long period of time in adulthood.

In a paper published in the journal Open Biology in December 2022, the team found that short-term deprivation of a single essential amino acid enhanced tolerance to the toxic substance nicotine in young adult D. melanogaster. But the effect of this approach on older D. melanogaster and how it affects long-term health is unclear.

The team added, "We don't yet know whether deprivation of a single amino acid for a short period of time also extends lifespan. If so, when do the amino acids need to be restricted, and for how long? This all needs to be explored further."

To investigate this, the team first assessed whether nicotine tolerance could be gained by briefly restricting isoleucine intake in D. melanogaster as they age. They maintained D. melanogaster on a nutritionally complete synthetic diet for one, two, three, or five weeks (their average lifespan is about nine weeks), respectively, and then transferred them to an isoleucine-deficient diet for one, three, five, or seven days, and then measured their survival when exposed to a lethal dose of nicotine.

Using this data to select the treatment regimen that offered the best protection from the toxin, the team found that a one-week isoleucine-restricted diet for D. melanogaster at mid-life (at three weeks) and later in life (at five weeks) significantly extended lifespan, regardless of their diets early and late in life.

Further revealing the mechanism by which short-term isoleucine restriction extends lifespan, the team found that endogenous damage in D. melanogaster is cleared during isoleucine restriction and that these effects cumulatively have beneficial outcomes on lifespan. These processes transiently induce autophagy and enhance protein homeostasis, thereby inhibiting aging.

This finding challenges existing notions about the stringency of dietary modifications for longevity and health benefits, and this relatively less stringent approach to isoleucine-restricted diets can provide benefits similar to those associated with broader dietary restrictions like traditional fasting.

The team says this study not only advances our understanding of the effects of diet on longevity in D. melanogaster, but also suggests a new, simpler avenue for aging research in other species. Specific amino acid restriction as a viable alternative to intermittent fasting opens the door to more targeted research into the mechanisms of dietary intervention.model organism D. melanogaster

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