An International Online Forum Provides Perspectives on Aging Mechanisms and Therapeutics

The proportion of elderly individuals in the world population continues to climb, raising several health-related challenges related to age-associated diseases for societies. To mitigate these challenges, burgeoning research geared toward healthy aging along with enhanced lifespan has provided longevity-related molecular mechanism insight for developing aging therapeutics.

The Aging Research and Drug Discovery (ARDD) Online Meeting On Aging Genetics and Therapeutics

Scheibye-Knudsen and a plethora of colleagues from numerous global universities published a meeting report in Aging describing key research on molecular mechanisms and existing therapeutic options for aging held 1^st to 4^th September 2020. Their notes touch on novel approaches for aging studies that include genetically-based aging clocks and analyses of changes to DNA like mutations that accumulate with passing years. To slow or reverse these genetic changes thereby mitigating aging itself, this scientific collective relay new findings on lifestyle alterations and pharmacological approaches for healthspan and lifespan modulation.

Using AI to Analyze DNA and Predict Biological Age

During the meeting, scientists presented information on the development of ways to analyze people’s DNA for aging research purposes. In particular, artificial intelligence (AI) research has led to the development of clocks to predict chronological and biological age—age in years and age according to physiological health, respectively. Along these lines, Dr. Steve Horvath from the University of California Los Angeles created an aging clock not only for chronological age but also the risk of death by measuring molecular tags on DNA called methylation. In the future, analysis of these DNA methylations in the context of biological aging can help predict biological age and the efficacy of effective treatment options slowing or reversing biological age progression.

DNA Sequence Changes May Facilitate Aging

Researchers have found other DNA changes that accumulate during aging, namely mutations in the DNA itself (point mutations) and rearrangements of DNA (genomic rearrangements). Jan Vijg from the Albert Einstein College of Medicine presented information on these mutations contributing to mortality—the occurrence of death—and disease. She showed that genetic sequencing of white blood cells in humans called B lymphocytes identified an exponential increase in mutation frequency with age. Given this information, Dr. Vijg surmised that de novo, or new, mutations accumulate from the earliest developmental stages to adulthood and old age.

Chromosome Alterations May Affect Fertility

Dr. Eva Hoffman of the University of Copenhagen in Denmark also presented research that highlights a reproductive lifespan. Dr. Hoffman’s work points to changes in fertility rates during aging from chromosome errors and aberrations in egg cells, oocytes, controlling natural fertility in humans. Current knowledge of reproductive aging from this research is paving the way for infertility interventions.

Reducing Specific Dietary Protein Building Blocks May Improve Metabolic Health and Delay Aging

Therapeutic options that may slow the accumulation of DNA methylation markers and mutations that facilitate aging include dietary strategies for metabolic intervention. Dr. Dudley Lamming of the University of Wisconsin presented research on the role of essential dietary amino acids—protein building blocks—in lifespan regulation. In the Lamming laboratory, researchers found a reduction in specific essential amino acids called branched chain amino acids (leucine, isoleucine, and valine) improves metabolic health and reduces body fat content (adiposity) in mice. The reduction of these amino acids also extended lifespan in experimental mouse models of aging called progeroid mice that mimic the human disease progeria—a condition where affected individuals look older than they are. If the findings from Lamming’s laboratory translate to humans, cutting out certain protein building blocks like leucine, isoleucine, and valine from our diets could be a way to improve metabolic health and possibly extend lifespan.

Enzyme Inhibitors May Enhance Healthy Aging

Dr. Eric Verdin of the Buck Institute presented pharmacological approaches based on the vital molecule for metabolism and cell health maintenance called nicotinamide adenine dinucleotide (NAD+). He has focused his research on an enzyme called CD38 that increases in abundance with age and consumes NAD+. Finding ways to suppress NAD+ consumption by inhibiting CD38 may lead to new methods to improve metabolism to facilitate healthy aging and increase lifespan.

The Future Looks Bright for Aging Research

“Conserved molecular pathways underlining aging can be manipulated using genetic, pharmacological and non-pharmacological approaches to significantly improve the healthspan and lifespan in model organisms, and perhaps humans,” stated Scheibye-Knudsen and colleagues in their meeting report. Importantly, a collaborative effort continues to grow between biotechnology companies and academia to accelerate therapeutic discoveries to combat aging. According to Scheibye-Knudsen and colleagues, the future of aging research is bright.