This week we wish to highlight the recently published Nature article from Juricic, P. et. al titled “Long-lasting geroprotection from brief rapamycin treatment in early adulthood by persistently increased intestinal autophagy”.

Domina’s systematic approach holds great promise as it aims to address complex, polygenic, multifactorial diseases - which actually is how most diseases should be characterized - they are not the result of a single gene or protein or cell type defect; indeed over-focused targeting has been one of the reasons for the failure of so many therapies against prevalent diseases. Instead, Domina aims to develop therapeutics that modulate and restore neuronal communication that directly impacts cognitive function, something that current approaches usually fall short of doing. That being said, recent acquisitions and partnerships between established pharma/biotech and startups focusing on neuropsychiatric/neurodegenerative disorders have garnered multi millions of dollars with the potential for billions of dollars in subsequent milestone payments, and we anticipate Domina should match these achievements in the coming years.

Given that mental disorders are the leading cause of disability compared to any other disease category already, perhaps the most impactful thing we could do for average life expectancy and longevity overall around the world would be to heavily focus on mental health. After all, the same distinction between lifespan and healthspan works for mental health as well - people don’t want to live longer if they are not healthy, and the same applies to mental wellness as well.

Cells are the fundamental units of life and disease. Many cell types maintain our bodies’ normal functions. Other anomalous cell types emerge to initiate disease. Association of cells with outcomes is largely missing because “diagnostically speaking” important cell types are very rare and routine identification and analysis of single cells is economically impractical. Sampling Human has built a breakthrough platform for clinically relevant access to the full spectrum of single cell data. The platform which uses “living cellular analyzers” or engineered microbes is: comprehensive, specific, sensitive and effective.

The hallmark of aging is the accumulation of damage in all compartments of the body associated with loss of homeostasis which manifests as compromised function. While clinical trials targeting the ageing process overall are still a few years away (hinging on whether aging is classified as a disease by the FDA), clinical trials targeting aging-associated diseases have been underway for years and we anticipate that they will only increase in number as the world's population continues to grey. Among the trials conducted thus far, those targeting sarcopenia, or the wasting away of muscle with age, has gotten a large amount of attention. Given the intricate nature of their design, these trials potentially serve as a template for future clinical trials targeting aging at large. Herein we aim to showcase the intricacies, nuances and considerations associated with the design of clinical trials targeting aging associated disease particularly through the lens of sarcopenia. 

Omic Aging Biomarkers or clocks are based on the simple principle that “your body keeps a count” in other words, a wide variety of environmental and biological factors cause dysregulation in your normal bodily functions which are imprinted at the very molecular levels of the body. It is thus worthwhile to go through a brief history of epigenetic aging clocks and also talk about how they can be made better.

COVID impacted all aspects of life including the world economy. One aspect which COVID, as a condition, highlighted was its ability to differentially impact the older populations, especially those with comorbidities. The vulnerability of older adults was brought to fore, and made clear that there exist key differences in the immune system across the lifespan. As we age, our immune cells weaken in their ability to fight infections and allow for opportunistic infections to ravage the elderly. In recent years we have come to better understand the reasons for this deficiency and T cells are a major player in this dysfunction. 

Clinical trial design, management and data analysis is undergoing a data revolution. With the advent of integration of large scale Omic data sets ranging from Clinical-omics (EHR data) down to single cell omics, the data deluge has both been a boon and bane. This data is only helpful in improving in the design and management of clinical trials if we are able to appropriately analyze and interpret it. Clearly, the bottleneck is no longer the data generation but rather the data processing and insight generation from this data. This has given way to a boom in development of computational tools, platforms and methods to solve these challenges which are now being integrated into the daily working of these trials.