When it comes to hunger, you may have heard of the concept of "intermittent fasting" in recent years. In biological research, the definition of "hunger" is more precise and complex. A 2021 review published in Nature Aging summarized that intermittent fasting scientifically falls under the category of "intermittent dietary regimens," which can be broadly divided into several types:
Alternate-day fasting (ADF) involves eating normally one day and consuming only water the next; the 5:2 diet means eating normally for five days a week and limiting intake to 500–700 calories on the remaining two days;
Time-restricted feeding (TRF) divides the day into two periods, restricting eating to the shorter window (typically 6–12 hours) and abstaining from food for the remaining time.
Other more extreme methods extend the fasting period to 1–2 days, but such practices are usually uncommon.
Overall, the key to intermittent dietary regimens is "intermittence"—periods of normal eating alternating with periods of restricted calorie intake. The "hunger phase" is crucial because it triggers a switch in metabolic mode.
In most mammals, excess glucose is stored as glycogen in the liver. After a period of fasting, as blood sugar levels drop, liver glycogen is gradually depleted to maintain blood glucose. When liver glycogen reserves become insufficient, the body switches metabolic modes, turning to ketones and fat as energy sources, commonly known as "fat burning."
Fat was originally a tool our ancestors used to store energy and withstand harsh winters when food was scarce. However, with continuously improving living standards, modern people experience hunger less often and overeat more frequently, leading to continuous fat accumulation and an obesity epidemic. According to World Health Organization (WHO) data, in 2022, one in every eight people was obese. As weight increases, the risk of various diseases also rises.
Therefore, "fat burning" itself can reduce the risk of modern "diseases of affluence." Some studies also suggest that this metabolic mode helps people better cope with stress and extend lifespan.
Furthermore, fasting can activate autophagy responses in the human body through related cellular signaling pathways, promoting the apoptosis of damaged, senescent cells. When eating resumes, the influx of nutrients can stimulate cell regeneration. In a sense, the cycle of fasting and refeeding is like giving cells an opportunity to renew and replace themselves. Consequently, corresponding tissues and organs become younger and healthier.
In recent years, researchers have increasingly recognized the benefits of cold exposure for animals. For example, the commonly used model organism, the nematode worm, shows a shortened lifespan when moved from a 20°C environment to a higher temperature. Conversely, relocating to an environment around 15°C can significantly extend its lifespan.
Similar results have been observed in mice. An environment merely 0.5°C higher than body temperature is enough to shorten their lifespan. Conversely, if the environment is 0.5°C lower than body temperature, the mice's lifespan can be extended. These studies clearly indicate intricate links between temperature and lifespan.
Scientists are trying to uncover the reasons behind this. A paper published last year in Nature Aging found that lower temperatures can activate proteasomes in nematodes to degrade aggregated pathogenic proteins. When they switched from nematodes to human cells, the same result was observed: at 36°C, this type of proteasome in human cells became activated, destroying disease-related proteins within the cells. This might explain some benefits brought by cold exposure.
Other explanations are more straightforward: in low-temperature environments, the rates of all biochemical reactions slow down, naturally decelerating aging; additionally, low temperatures can also promote fat burning, solving many problems through weight loss.
These explanations sound reasonable, but it must be noted that our understanding of cold exposure is still quite preliminary, with many mysteries yet to be solved. For instance, a collaborative study between the University of Michigan and Huazhong University of Science and Technology found that in adult nematodes, low temperatures can activate a protein called TRPA1 located on nerve cells and fat cells, initiating a series of biochemical reactions that ultimately activate the longevity gene DAF-16/FOXO.
Interestingly, in nematode larvae, the same environment yields completely opposite effects. In fact, larvae living in warmer environments have a lifespan about 20% longer. These seemingly contradictory data also tell us that there is much more to explore regarding temperature's impact on organisms.
Existing scientific research can only explain what reactions occur in organisms facing hunger or cold, and how these may potentially affect health, but cannot answer "why it is this way." People have had many speculations. One explanation suggests that modern society has developed too rapidly, and the body hasn't kept up with this pace.
If we imagine the human body as a smartphone, then the genome is our hardware, determining our performance upper limit; various stimuli from the environment are like software, undergoing rapid upgrades and iterations over the past few thousand years. Today, we can sit for long hours in temperature-controlled offices, reach for various foods and sugary drinks with ease, and no longer need to roam around like our hunter-gatherer ancestors. We have built a comfortable environment with our own hands, yet it leaves the body feeling disoriented. Some so-called adversities today might actually be closer to the environments familiar to the human body, allowing it to return to a healthier state.
Of course, the above explanation can only be considered a hypothesis, awaiting more evidence for confirmation. However, for modern individuals seeking to improve their health, there's no need to fully understand the underlying mechanisms. Perhaps simply following some human-supported practices (such as intermittent fasting, short bursts of high-intensity exercise, etc.) can yield benefits.
Additionally, we can await the latest achievements from the scientific community. At a previous American Chemical Society spring meeting, researchers from Washington University in St. Louis found a compound that can mimic the effects of exercise on the human body. This undoubtedly offers a novel health approach using drugs to simulate adversity. We also look forward to more such drugs in the future, allowing us to enjoy the same health benefits without experiencing uncomfortable sensations like hunger and cold.
