At the Optispan Podcast, we aim to help you become your own detective of research in the geroscience field and beyond. Critical thinking is our compass. We want to help you dig into every aspect of a study: are the methods they used solid? Was the sample size big enough? Did they crunch the numbers right? What's the most reasonable interpretation of the data? Might a conflict of interest skew the results?

In Part II of a two-part series about a recent study of how a supplement called "Leap Years" affects canine cognitive function, Matt takes a magnifying glass to a bioRxiv preprint describing the clinical trial's methodology and findings. Beginning with a sentence-by-sentence dissection of the study's abstract, he describes various things he finds unusual or questionable about the way researchers ran and publicized the clinical trial: exclusion of certain data, a lack of disclosure around the supplement's ingredients, the use of an assessment tool that was not validated for its intended purpose, and more. He discusses conclusions we can actually draw from the study based on the information the researchers have supplied, and whether or not he would give the supplement to his own dog.

This episode is Part II of a two-part series. In part I, Matt talks about the press release announcing the drug's potential ability to reverse age-related decline and improve cognitive function in dogs, as well as the importance of interrogating bold advertising claims rather than taking them at face value.

Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!

LeapYears

You can get more information about and purchase the LeapYears product here. Animal Biosciences, the company selling the product, describes LeapYears as "the only dual action dog supplement system that targets aging at the source – the cellular level." The website provides several resources about dog aging, cellular senescence, NAD boosters, and its clinical trial results.

A Randomized, Controlled Clinical Trial Demonstrates Improved Cognitive Function in Senior Dogs Supplemented with a Senolytic and NAD+ Precursor Combination

This is the preprint upon which the LeapYears product is based. Preprints are drafts of full papers that have not yet undergone peer review, a process of ensuring the credibility, validity, and reliability of published research by subjecting it to rigorous evaluation by independent experts. Preprint results can be exciting, valid, and spark interesting discussions, but should be interpreted with caution. This preprint provides some insight into the nuances of the clinical trial that led to the product's eventual introduction to the pet market.

NAD+ homeostasis in human health and disease

Nicotinamide adenine dinucleotide (NAD), an essential cofactor present in all living cells that modulates several metabolic pathways, became more prominent in the scientific literature in the last two decades when it was highlighted as a crucial component of sirtuin function. In this review, the authors discuss current knowledge of NAD's role in various human diseases as well as current therapeutic strategies that target NAD.

Age-Dependent Decline of NAD+—Universal Truth or Confounded Consensus?

This article questions the consensus view that NAD levels decline with age by examining NAD changes in various species, including yeast, worms, rats, mice, monkeys, and humans. They find that the evidence for age-dependent NAD declines is limited, in part due to a relative paucity of studies assessing how NAD levels change with age, and in part due to the many discrepancies in the literature about this topic, even down to the level of individual tissues. They note that human studies of age-related NAD changes are particularly limited and inconclusive, and call for larger-scale studies of and greater nuance in discussing the relationship between NAD levels and age.

A common signature of cellular senescence; does it exist?

At its core, cellular senescence represents a state of irreversible growth arrest in cells. Pinpointing a universal definition of senescence is challenging, however, because senescence manifests differently across cell types and contexts and encompasses a spectrum of phenotypic changes beyond just growth arrest, including alterations in gene expression, metabolic activity, and the secretion of pro-inflammatory factors. Subsets of senescent cells may exhibit distinct properties and functions. This review examines the question of whether there exists a common signature of cellular senescence.