Exposure to Cold as an Approach to Modestly Slow Aging
Mild stresses are observed to slow aging in short-lived species, sometimes dramatically. Low nutrient intake, heat, cold, toxins, and anything else that makes cells react by upregulating maintenance processes tends to produce sweeping improvements in metabolism, reduced inflammation, and a range of other benefits. This results in extended healthy life span. Unfortunately, long-lived species such as our own do not exhibit anywhere near the same degree of extended life, even while the cellular biochemistry of the response to mild stress looks very similar. The underlying reasons for this difference have yet to be established.
Although the longevity benefits of low temperatures were documented over a century ago, the precise mechanisms by which cold influences lifespan and healthspan are not fully understood. The prevailing hypothesis suggests that cold-induced longevity is mainly attributed to a slowdown in the rate of biochemical reactions and metabolic processes, leading to reduced energy expenditure and a decelerated pace of physiological activities. Recent research, however, has uncovered more intricate mechanisms through which cold exposure can extend lifespan and improve health.
Cold exposure has been shown to impact several key physiological processes related to aging. One of the major mechanisms is its ability to reduce chronic inflammation, a condition often referred to as "inflammaging". Chronic, low-grade inflammation is a hallmark of aging and is associated with the development of various age-related diseases, including cardiovascular diseases, diabetes, and neurodegenerative disorders. It has been reported that cold exposure can mitigate inflammation by modulating immune responses and reducing the production of pro-inflammatory cytokines in healthy individuals as well as patients with inflammatory diseases. These cytokines are typically elevated in chronic inflammation and are associated with various age-related diseases. By lowering their production, cold exposure may help decrease systemic inflammation.
Another significant aspect of aging is oxidative stress, which results from the accumulation of reactive oxygen species (ROS) that causes damage to cellular components and contributes to cellular aging and various diseases. The free radical theory of aging posits that oxidative stress is a major driver of the aging process. Cold exposure has been shown to reduce oxidative stress and enhance the body's antioxidant defenses, thereby reducing inflammation and protecting cells from damage.
Metabolic regulation is also profoundly affected by cold exposure by increasing energy expenditure and altering metabolic pathways. Activating brown adipose tissue (BAT) through cold exposure increases energy expenditure and improves metabolic health. This process enhances insulin sensitivity, promotes lipid metabolism, and helps to regulate glucose metabolism, thereby mitigating inflammatory responses associated with metabolic dysfunction. These metabolic pathways play a crucial role in maintaining overall health and longevity. Additionally, recent studies have also revealed that cold exposure can activate proteasomes through PA28γ/PSME3 pathway, enhancing protein degradation and reducing disease-related protein aggregation.
Despite the promising short-term benefits of cold exposure, the long-term effects remain unclear. Epidemiological studies present a paradox: while short-term cold exposure seems to offer health benefits, populations living in high-altitude cold environments face an increased health risks, including higher mortality rates and a greater incidence of cardiovascular diseases. This complexity underscores the need for further research to fully understand the relationship between cold exposure and aging.