Hormesis for Healthy Aging and Longevity
Exercise is possibly the worst thing you can do to your body on a biochemical level – it creates all sorts of oxidative stress, kills cells, and causes damage. However, the period after exercise leads to the initiation of regenerative pathways which strengthen the body beyond just the muscles. Metabolism, cognition, and the immune system are several systems which benefit from exercise, and this illustrates the concept of hormesis. When we induce specific types of stress, it leads to a beneficial effect via the innate regenerative mechanisms that already exist within us. Systems such as the Heat shock response and DNA damage response can be harnessed for our benefit. 7 major regenerative pathways regulate these responses.
Aging is a complex and dynamic process. The current paradigm focuses on specific drugs and individual pathways such at Tor or telomeres. However, when it comes to interventions it is nearly impossible to get results from these very narrow approaches due to the adaptive nature of biological systems.
By creating repeated mild stress in humans, we can induce general regeneration systems to improve the homeodynamic state of a person. By repeatedly inducing a heat shock response to cells in a lab, Suresh was able to see improvement in health and a reduction in signs of aging. Similar effects have been seen since then in subsequent experiments.
The hormetic response is often shown as a J shaped curve, indicating that small doses of a stressor are positive while large doses are detrimental.
How can we measure health without involving the concept of disease? We need to have a better understanding of the nature of health, which comes back to the issue of biomarkers of aging. The frailty index is not sufficient.
We need to measure the effects of combinations of hormetic interventions. When using curcumin on cells then inducing heat shock, the cells had 5-6 times better outcomes. When heat shock was done prior to curcumin, the cells generally died. These interactions need to be investigated further.