Much of the comparative biology of aging involves study of long-lived mammals in an attempt to understand which mechanisms determine species longevity. It is possible that a better understanding of this biochemistry might form the basis for therapies, though this is by no means guaranteed. It is quite possible that mechanisms of species longevity will be very difficult to move between species, or to influence in another species without negative consequences. The past few decades of research into mimicking the beneficial responses to exercise and calorie restriction well illustrate that reworking the engines of metabolism is a very challenging endeavor. Few inroads have been made despite enormous effort and expenditure. This is one of many reasons as to why I favor the damage repair approach: don’t try to engineer a better metabolism, keep the one we have, and repair the forms of damage that impair it with age.

One important question in aging research is how differences in genomics and transcriptomics determine the maximum lifespan in various species. Despite recent progress, much is still unclear on the topic, partly due to the lack of samples in non-model organisms and due to challenges in direct comparisons of transcriptomes from different species. The novel ranking-based method that we employ here is used to analyze gene expression in the gray whale and compare its de novo assembled transcriptome with that of other long- and short-lived mammals.

Gray whales are among the top 1% longest-lived mammals. Despite the extreme environment, or maybe due to a remarkable adaptation to its habitat (intermittent hypoxia, Arctic water, and high pressure), gray whales reach at least the age of 77 years. In this work, we show that long-lived mammals share common gene expression patterns between themselves, including high expression of DNA maintenance and repair, ubiquitination, apoptosis, and immune responses. Additionally, the level of expression for gray whale orthologs of pro- and anti-longevity genes found in model organisms is in support of their alleged role and direction in lifespan determination. Remarkably, among highly expressed pro-longevity genes many are stress-related, reflecting an adaptation to extreme environmental conditions.

The conducted analysis suggests that the gray whale potentially possesses high resistance to cancer and stress, at least in part ensuring its longevity. This new transcriptome assembly also provides important resources to support the efforts of maintaining the endangered population of gray whales.