A Report from the 7th Annual Aging Research and Drug Discovery (ARDD) Meeting
Most 2020 conferences were held online as a result of COVID-19, curtailing the networking, discovery, and serendipitous discussion that is most of the point of attending a conference. Presentations were still given and research results announced, however. It remains useful to glance over conference reports for a sense of the mood and focus of the academic research and clinical development communities.
A tremendous growth in the proportion of elderly people raises a range of challenges to societies worldwide. Healthy aging should therefore be a main priority for all countries across the globe. However, science behind the study of age-associated diseases is increasing and common molecular mechanisms that could be used to dissect longevity pathways and develop safe and effective interventions for aging are being explored. The 7th Annual Aging Research and Drug Discovery (ARDD) meeting was held online on the 1st to 4th of September 2020. The meeting covered topics related to new methodologies to study aging, knowledge about basic mechanisms of longevity, latest interventional strategies to target the aging process as well as discussions about the impact of aging research on society and economy.
Molecular and therapeutic importance of NAD+ metabolism for aging was underlined in multiple talks at the ARDD meeting. Eric Verdin, Buck Institute, USA introduced the concept of competition among major NAD+-utilizing enzymes for NAD+ that may explain its age-dependent decline across multiple tissues. Evandro Fei Fang, University of Oslo, Norway underlined the importance of the NAD+-mitophagy / autophagy axis in aging and neurodegeneration and presented data on how impairment of this axis contributes to the progression in accelerated aging diseases as well as in the most common dementia, the age-predisposed Alzheimer's disease.
Another recently uncovered molecule that is able to improve mitochondrial function via mitophagy is Urolithin A, a gut microbiome metabolite known to improve mitochondrial function via mitophagy, increases muscle function, and possesses geroprotective features across multiple species. Pénélope Andreux, Amazentis, Switzerland presented results from a double blinded placebo controlled study showing that urolithin A administration in healthy elderly people is safe and was bioavailable after single or multiple doses over a 4-week period. Oral consumption of urolithin A decreased plasma acylcarnitines, a sign of improved systemic mitochondrial function, and displayed transcriptomic signatures of improved mitochondrial and cellular health in muscle.
Notably, studies of multiple interventions in different aging models include examinations of various markers of cellular senescence. Its significance for the aging process has been shown multiple times across model systems. Senescent cells occur in all organs, including post-mitotic brain tissues, during aging and at sites of age-related pathologies. The SASPs of senescent cells lead to chronic inflammation and may contribute to the development of various cellular phenotypes associated with aging and diseases. Hence, a novel class of drugs targeting senescent cells are emerging, including senolytics (selective elimination of senescent cells) and senomorphics (selective modification of senescent cells).
Several strategies were proposed to target senescent cells. Marco Demaria, ERIBA, Netherlands, demonstrated the important role of oxygen in the development of the senescence phenotype. Data illustrated that growth arrest, lysosomal activity and DNA damage signalling were similarly activated in senescent cells cultured at 1% or 5% oxygen, but induction of the SASP was suppressed by low oxygen. Tissues exposed to low oxygen also expressed a lower SASP than more oxygenated ones. It was demonstrated that hypoxia restrains SASP via AMPK activation and mTOR inhibition, and that intermittent treatment with hypoxia mimetic compounds can serve as a potential strategy for the reduction of SASP in vivo.
Current knowledge shows that aging is a very complex but plastic process. 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. A collaborative effort between academic research with a growing number of emerging biotech companies, as well as increased investment funds to accelerate discoveries, will most likely bring effective aging pharmaceuticals in the near future.