Breakthroughs in medicine and technology account for a global increase in life expectancy, yet improvements in quality of life for the elderly population lag far behind. Human longevity coupled with poor healthspan expectations is a significant challenge facing anti-aging medicine and the future of population health. Targeted therapeutic interventions and preventive care protocols are necessary to mitigate the sharp rise in age-related disease and disability accompanying longer life expectancy.
Different designer diamines, lab-derived amines with two amino groups, are increasingly being studied for their potential to enhance the healthspan by promoting mitophagy and protecting cells against oxidative damage. In a recent study, researchers from the Hebrew University of Jerusalem evaluated a new molecule for its potential to prevent age-related diseases and increase life expectancy and wellness. Their findings were published in Autophagy and outline the role of mitophagy in age-related disease and the promising protective effect of diamines.
Mitochondrial Dysfunction and Mitophagy
Impaired mitochondrial function constitutes one of the primary pathogenic events underlying various age-related diseases such as Alzheimer’s, Parkinson’s, and sarcopenia. Mitochondrial dysfunction is characterized by irregular mitochondrial morphology, insufficient adenosine triphosphate production, mitochondrial DNA mutation accumulation, heightened mitochondrial reactive oxygen species production, and consequent oxidative damage.
When the degradation process of dysfunctional mitochondria – or mitophagy – is impaired, the buildup of defective mitochondria can result in cellular damage, neurodegeneration, and the development of mitochondrial diseases. Thus, accelerating the aging process while diminishing healthspan.
A review article published in Frontiers in Cell and Developmental Biology describes mitophagy as a “mitochondrial quality control mechanism enabling the degradation of damaged and superfluous mitochondria.” This process prevents the detrimental effects of damaged mitochondria accumulation and reinstates cellular homeostasis in response to stress. However, this mechanism declines with age, resulting in cell dysfunction and deterioration in tissue activity.
Current evidence indicates that mitophagy is significantly impaired in aging and age-related diseases, including cardiovascular disease and cancer. Therapeutic interventions aiming at mitophagy induction may potentially ameliorate age-related diseases, promoting longevity and healthspan.
Inducing Mitophagy with Designer Diamines
The augmentation of mitophagy is emerging as a strategy for preventing age-related diseases and enhancing human healthspan. The team of researchers from the Hebrew University of Jerusalem based their study on an established microphagy-promoting agent, the scaffold of spermidine, and designed structurally related compounds.
Led by Professors Einav Gross and Shmuel Ben-Sasson of the Faculty of Medicine at the university, the researchers evaluated the efficacy of their molecules on a model-organism. They examined the impact of various therapies on longevity and quality of life, searching for a solution to protecting the organisms and human cells from damage.
The team identified 1,8-diaminooctane (VL-004) as an agent capable of inducing mitophagy and enhancing healthspan; it even exceeded spermidine in its ability to promote mitophagy and protect against oxidative stress.
Gross and Ben-Sasson’s study may have far-reaching future implications, particularly for the treatment of currently incurable conditions and age-related diseases. The ability to ameliorate the degenerative processes innate to the aging process could halt and reverse upward trends in the prevalence of age-related diseases such as Alzheimer’s disease, Parkinson’s disease, heart failure, and sarcopenia.
According to the study’s authors, the initial structural characterization implies simple rules for designing molecules with improved bioactivity, paving the path for a new generation of agents for healthy aging.
The findings also revealed that such molecules can be used preventively and are user-friendly .” In the future, we hope we will be able to significantly delay the development of many age-related diseases and improve people’s quality of life,” shared Ben-Sasson in a press release accompanying the study.
Gross and Ben-Sasson are working to advance their research and translate it into therapeutic interventions to minimize the burden of age-related diseases on patients, their families, and our health care systems.
Designer diamines have previously been shown to induce mitophagy, but the mechanism underlying this phenomenon has yet to be investigated at length. In addition to helping extend longevity, these compounds also have potential uses for restoring cellular health, slowing aging, and treating aging-related degenerative diseases. More research is needed before designer diamines can be brought to market, but this study suggests a positive future for mitophagy-based treatments and significant potential value for the global aging population.