Discovering sirtuin longevity proteins in early branches of animal life

+ pathways in model organisms, including mammals, fruit flies (Drosophila melanogaster), nematodes (Caenorhabditis elegans), and yeast (Saccharomyces cerevisiae). Arrows indicate the regions of the cell where sirtuin activity has been described in each organism. Credit: Molecular biology and evolution (2022). DOI: 10.1093/molbev/msac192″ width=”800″ height=”530″/>

Overview of the different sirtuin/NAD+ pathways in model organisms, including mammals, fruit flies (Drosophila melanogaster), nematodes (Caenorhabditis elegans), and yeast (Saccharomyces cerevisiae). Arrows indicate the regions of the cell where sirtuin activity has been described in each organism. Credit: Molecular biology and evolution (2022). DOI: 10.1093/molbev/msac192

Animals on the early branches of the tree of life, such as jellyfish and sea sponges, defy the usual conventions of aging. Some show the ability to regenerate damaged or missing tissues, halt or reverse aging, and in the case of at least one jellyfish species a form of ‘immortality’. A new study from researchers at the University of California, Davis and Harvard Medical School takes a detailed look at a group of proteins called sirtuins, linked to protection against cell damage and aging, in these animals and throughout the animal kingdom. The work was published on September 6 in Molecular biology and evolution.

David Gold, assistant professor in the Division of Earth and Planetary Sciences, UC Davis College of Letters and Science; and David Sinclair, Harvard Medical School, wanted to reconstruct the evolution of sirtuins with a special focus on the little-studied animals on the early branches of life.

“The big advantage is that there was radiation from sirtuins early in the evolution of animals, with a significant amount of loss over time. If you just look at model organisms (i.e. yeast, roundworms, fruit flies, mammals) it seems like the number of The number of sirtuins has increased over the course of evolution, but we are describing several previously unrecognized sirtuins that are mainly found in early branching animals such as jellyfish, sea anemones and sea sponges,” Gold said.

Sinclair’s lab originally helped discover the link between sirtuin and aging in yeast and the link between sirtuin proteins and longevity in mammals.

“One of my specialties is reconstructing the evolution of gene families over long timescales. So I suggested that we examine the distribution of sirtuins in early animals to see if there is a link between sirtuin copies and their unusual longevity,” he said. gold.

More than 15,000 sirtuin proteins have been identified in more than 6,000 species of living things. Sirtuins are involved in the metabolism of nicotinamide adenosine dinucleotide, or NAD, which plays a central role in energy metabolism, DNA repair and other vital processes in cells. Sirtuins and NAD are involved in two main pathways, each with a different protein, NAMPT or PNC1. NAMPT pathways are found in mammals and bacteria while PNC1 is found in fruit flies, yeast and roundworms. In addition, most eukaryotes have multiple versions of sirtuin.

Sirtuins appear early in evolution

Because they are so important, sirtuins, NAMPT and PNC1 must have appeared very early in life’s evolution. But since then they have gone through many changes and variations in the different branches of life.

Gold and Sinclair searched for sirtuin-like proteins from various animals in public databases and collected them on an evolutionary tree. They focused on the early branching animal phyla: Porifera (sea sponges), Ctenophora (comb jelly), Placozoa (amoeba-like animals), and Cnidaria (sea anemones, corals, jellyfish, and hydras).

The researchers discovered several new sirtuins, especially in the early branching animals. The last common ancestor of all animals had at least nine sirtuins, they found. Since that distant time, there has been a complex pattern of gains and losses. New sirtuin genes formed from duplications of old ones. Some families of proteins disappeared in one line of animals, but survived in others to this day.

The first animals had genes for both NAMPT and PNC1, but these have repeatedly disappeared from lines. There doesn’t seem to be a clear pattern as to why a modern group of animals has lost or retained either, or why it has some sirtuin protein families but not others, Gold said. Also, there doesn’t seem to be a direct link between a particular sirtuin family and longevity, he said. However, the discovery of additional sirtuin genes in early branching animals is exciting and could play a key role in their longevity and unique life history strategies.

“We don’t yet know what the link is between these extra copies of the sirtuin gene and the unusual life histories of early branching animals. That’s the next step,” Gold said.


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More information:
David A Gold et al, Sirtuin Evolution at the Dawn of Animal Life, Molecular biology and evolution (2022). DOI: 10.1093/molbev/msac192

Quote: Discovering Sirtuin longevity proteins in early branches of animal life (2022, September 22) retrieved September 22, 2022 from https://phys.org/news/2022-09-sirtuin-longevity-proteins-early-animal.html

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