Secrets of Longevity Unveiled in Ancient Mollusks
In 2006, scientists discovered an extraordinary ocean quahog mollusk off the coast of Iceland, known as Ming or Hafrun. Initially estimated to be 405 years old, subsequent research revealed Ming's astonishing age of 507 years, making it one of the oldest non-colonial animals with a precisely determined age. The name of this 87x73 mm (3.4 × 2.9 inches) mollusk reflects its birth during China's Ming Dynasty and its enigmatic life in the ocean. Despite its significance, Ming's long life came to an end in 2006 when researchers unintentionally froze the specimen, shedding light on the secrets of extreme longevity in the animal kingdom.
Why these mollusks live so long remains an intriguing question. It turns out they possess a stable proteome, meaning their proteins maintain their structure even under various stresses like high temperatures and oxidants.
A stable proteome in simple terms means that the proteins in an organism remain structurally intact and functional even when the organism is exposed to various stresses or challenges.
This is significant because protein dysfunction, known as proteostasis disruption, is considered a key hallmark of the aging process. Consequently, a stable proteome emerges as a characteristic feature shared among all long-lived species, such as mole-rats, bats, whales, and others. These findings are corroborated by E. Philipp and colleagues' research.
In the gill and mantle tissues of the Arctica islandica mollusk, intriguing changes occur throughout its life. During its early development when the mollusk is growing and preparing for reproduction, specific biological processes like the activity of catalase, citrate synthase, and glutathione levels decrease.
Catalase is an enzyme that plays a crucial role in breaking down hydrogen peroxide (H2O2) into water (H2O) and molecular oxygen (O2). This process is one of the ways the body combats oxidative stress and prevents cell damage from hydrogen peroxide, which can be toxic to cells at high concentrations.
Citrate synthase is an enzyme that plays a key role in the Krebs cycle (also known as the citric acid cycle) inside the mitochondria of cells. This cycle is involved in metabolism and energy production, converting acetyl-CoA and oxaloacetate into citrate and initiating a sequence of chemical reactions that generate energy in the form of ATP.
Glutathione is an antioxidant present in the body's cells that performs several important functions. It protects cells from oxidative damage by helping to combat free radicals and other oxidative stressors. Glutathione also participates in various cellular processes, including detoxification and immune system regulation.
However, when the mollusk reaches maturity (around 32 years), these processes become stable and remain unchanged for an extended period (over 150 years). On the other hand, the activity of superoxide dismutase, another biological process, remains high throughout the mollusk's entire life. These findings suggest that the Arctica islandica mollusk possesses a high capability to combat free radicals, which may explain its remarkable longevity. You can find these findings in the scholarly work titled "Imperceptible Senescence: Understanding Aging in the Ocean Quahog Arctica islandica" authored by Doris Abele, Julia Strahl, Thomas Brey, and Eva E R Philipp.
In study titled "Low Hydrogen Peroxide Production in Mitochondria of the Long-Lived Arctica Islandica: Underlying Mechanisms for Slow Aging," a team of researchers led by Daniel Munro, Nicolas Pichaud, Frédérique Paquin, Vincent Kemeid, and Pierre U Blier made a fascinating discovery. They found that the mitochondria, which are the cell's energy-producing powerhouses, in long-lived Arctica islandica mollusks produced significantly less H₂O₂ compared to the mitochondria of two shorter-lived species. This intriguing observation suggests a possible link between the reduced production of this harmful molecule and the extended lifespan of these mollusks. Furthermore, the scientists hypothesize that changes in the functioning of specific cellular components in these mollusks may play a pivotal role in this process.
In 2012, scientists conducted a groundbreaking study comparing the ability of bivalve mollusk species with varying lifespans to resist genotoxic stressors (titled "Resistance to Genotoxic Stresses in Arctica islandica, the Longest Living Noncolonial Animal: Is Extreme Longevity Associated With a Multistress Resistance Phenotype?"). They aimed to test the hypothesis that extremely long-lived bivalve mollusks do not possess unique resistance to oxidative stress but exhibit a broader multi-stress resistance phenotype.
The researchers assessed the susceptibility (in terms of organism mortality) to genotoxic stressors, including topoisomerase inhibitors, agents that cross-link DNA or disrupt genome integrity through alkylation or DNA methylation, and mitochondrial oxidative stress. They conducted these experiments using three bivalve mollusk species with significantly different lifespans: Arctica islandica (ocean quahog), Mercenaria mercenaria (northern quahog), and Atlantic bay scallop, Argopecten irradians irradians (with maximum species lifespans of >500, >100, and ~2 years, respectively).
The results consistently showed that the short-lived A. irradians was significantly less resilient compared to the two long-lived species. Notably, Arctica islandica consistently displayed higher resilience than Mercenaria mercenaria to mortality induced by oxidative stressors, as well as a DNA methylating agent, nitrogen mustard, and DNA-alkylating agent methyl methanesulfonate. Conversely, M. mercenaria tended to be more resilient to epirubicin and genotoxic stressors that cause DNA damage by inhibiting topoisomerases.
These findings provide additional support for the hypothesis that there is a connection between longevity and overall resistance to multiple stressors, not limited to oxidative stress.
As pointed out by the authors, the genomic stability observed in long-lived mollusks may be closely related to their near absence of pathologies associated with mutagenesis and tissue regeneration. This characteristic is also common among many other long-lived species, reaffirming that genomic stability is an inherent trait of longevity.
The genome is the complete set of genes and genetic information necessary for the development, growth, and functioning of an organism. Genomic stability means that this genetic information remains unchanged and is not subject to unwanted alterations, mutations, or damage. Disruptions in genomic stability can lead to mutations, cancer, and other diseases.
Scientific studies of the longest-living animals on Earth confirm that long-lived mollusks can achieve their remarkably extended lifespan through the reduction of oxidative stress, genomic and proteomic stability, as well as control over lipid peroxidation.
Photo by febb, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=47254998
