Prior to the advent of senolytic therapies, all of the methods shown to improve long-term health and increase life span in laboratory animals involved triggering increased levels of stress response mechanisms. These include cell maintenance activities such as autophagy, responsible for recycling damaged cell components and removing unwanted metabolic waste. Calorie restriction is the best studied of means to beneficially stress an organism, but it is far from the only approach that might be taken. Inducing transient ischemia, a reduction in blood flow to a tissue, has been shown to trigger many of the same stress response mechanisms, and researchers here review the evidence from this part of the field.
Recently, attention has been focused on an innovative approach, termed as ischemic conditioning (IC), particularly remote ischemic conditioning (RIC), knowing that repetitive, transient and sublethal series of ischemia-reperfusion (IR) bursts can trigger endogenous protection and tolerance against subsequent ischemic threats. RIC may benefit multiple organs of the body at the same time. It seems to be a promising non-pharmaceutical and non-surgical therapy for preventing and treating age-related systemic vascular diseases such as combined lesions in the brain, heart, and kidney, and also arteriosclerosis-induced neurodegenerative disorders.
Decreased physiological reserve and tissue resilience are characteristics of biological ageing, which render the human system more susceptible to pathological threats. Given the fact that elderly patients usually have at least two afflicted organs or tissues, therapeutic approaches with systemic actions (inducing protective responses in a wide range of organs and tissues) are warranted. The emerging area of RIC builds upon this foundation. The capability of this non-pharmaceutical and non-surgical intervention to protect vital organs simultaneously by enhancing the body's powers to adapt to pathological threats could provide a safe, less burdensome, minimally-invasive way for ageing-related disorders. Currently, RIC is being evaluated in a variety of clinical settings such as cerebrovascular disease, coronary artery disease, and renal injury that predominantly influence the older population.
To date, regarding the safety and tolerability of the methodology, no RIC-associated adverse events have been reported in the published clinical studies. Although the prospect of clinical transformation of RIC on multi-organ protection is promising, challenges still exist. For instance, although previous experimental work has implied that the number and duration of IR cycles might affect the efficacy of RIC, there is a paucity of clinical data comparing the effectiveness of different RIC protocols, and no convincing evidence of the most favorable conditioning strategy has been established.
Future experimental or clinical work should focus on addressing the issues that may influence the translation of RIC from test bench to bedside, such as identifying the protective mechanism underlying ischemic conditioning, optimizing the conditioning regimen, establishing biomarkers to accurately evaluate the efficacy of RIC, and figuring out the impact of potential comorbidities, medications, and other factors on RIC.