A study shows that exposure to cold temperatures activates a system specialized in eliminating protein aggregates involved in cellular aging.
It has been known for several years that a moderate reduction in body temperature is associated with longer life expectancy. This is particularly noticeable in cold-blooded animals (poikilotherms) such as certain species of fish, whose low temperatures (15 ° C) significantly increase life expectancy.
This phenomenon is also observed in homeotherms (warm-blooded animals) such as rodents: if mice are exposed to cold to reduce their body temperature by 0.5 °C, their lifespan is extended, while if we increase the temperature by 0.5, their lifespan is shortened Increase °C.
It is also possible that slightly cooling the body is beneficial to human health: for example, although it has long been assumed that our normal body temperature is 37 ° C (with fluctuations of fractions of a degree throughout the day), recent data suggests this this temperature has fallen by about 0.03 °C per decade since the Industrial Revolution and is now about 36.6 °C.
It has been suggested that this decline, which may reflect a decrease in chronic inflammation through better treatment of infections and the use of anti-inflammatory drugs, may contribute to the increase in life expectancy observed over the past 150 years. (1)
To better understand how cold can improve longevity, German researchers studied the protein aggregates that accumulate in cells during aging.
These aggregates, which arise from defects in the three-dimensional configuration of proteins that make them insoluble, are very toxic to the cell and, over time, lead to loss of function in the affected organs. (2)
This is particularly noticeable in neurodegenerative diseases such as Alzheimer's disease, Huntington's disease or amyotrophic lateral sclerosis (ALS) (known as Lou Gehrig's disease or Charcot disease), all of which are caused by the accumulation of abnormal clusters of certain proteins become.
Since cells contain an enzymatic system specialized in eliminating these aggregates (the proteasome), they wanted to find out whether cold activates this proteasome and allows these aggregates to be eliminated to protect the cell from their toxicity.
It appears that this is indeed the case. (3)
In an animal model containing the typical aggregates of Huntington's disease or ALS, a decrease in temperature from 20 to 15 °C leads to activation of the proteasome and complete elimination of these aggregates, which is associated with increased life expectancy.
An identical phenomenon is observed when human cells derived from an ALS patient are exposed to a temperature of 36 °C, suggesting that the mechanism for eliminating defective proteins that can be activated by cold is very ancient and preserved during evolution.
Clean the cell
Human body temperature is kept constant by an extremely sophisticated control system and therefore it is of course not possible to lower our body temperature for long periods of time.
On the other hand, an interesting observation from the study is that it would be possible to circumvent this limitation: the researchers have actually observed that even at normal temperature (37 ° C), we can stimulate the elimination of toxic aggregates by increasing the concentrations of one Protein (called PSME3), which is involved in the activation of the proteasome.
By developing therapies that manage to recreate this phenomenon, we could not only slow down a central process of biological aging, but above all allow the cleansing of the cell of toxic aggregates that are responsible for several serious diseases, especially at the neurological level are.
♦ (1) Protsiv M et al. Falling human body temperature in the United States since the Industrial Revolution. Elife 2020:9:e49555.
♦ (2) Cuanalo-Contreras K et al. Extensive accumulation of misfolded protein aggregates during natural aging and senescence. Forehead. Aging neuroscience. 2022; 14:1090109.
♦ (3) Lee HJ et al. Cold temperatures extend life expectancy and prevent disease-related protein aggregation through PA28y-induced proteasomes. Nat aging 2023; 3:546-566.