Fight Aging!

Species that exhibit negligible senescence tend to be long-lived, but more interestingly appear to exhibit few to none of the functional declines of degenerative aging until very late in life, quite unlike the situation for most mammals, and particularly for humans. One can argue that the most useful species that exhibit negligible senescence are those with near relative species that age more normally. The closer the relative, the more likely it is that comparing the biochemistry of the two will lead to new knowledge regarding aging. So naked mole rats versus other, less long-lived mole rats, Brandt's bat versus other shorter-lived small bats, or as in today's open access paper, the red sea urchin versus short-lived urchin species.

Whether this work on the comparative biology of aging can cost-effectively produce a basis for useful therapies in human medicine remains an open question. Research into the biochemistry of naked mole rats, probably the closest negligibly senescent species to our own species, has yet to yield a way to build useful treatments for aspects of human aging. The one experiment conducted to date involving the transfer of naked mole-rat genes into mice didn't produce the hoped-for sizable gains. It may turn out to be slow, expensive, and challenging to work towards this sort of modification of our biochemistry, as compared with the more standard approaches to medical research

Genomic signatures of exceptional longevity and negligible aging in the long-lived red sea urchin

A tremendous variety of life history strategies have evolved across the animal kingdom, including some animals that achieve remarkably long lifespans (on the order of centuries) without the physiological decline that typically accompanies aging. This phenomenon, referred to as negligible senescence, is characterized by a lack of increased mortality rate or decreased fecundity as an organism ages, in combination with maintenance of physiological function and disease resistance. Animals with extraordinary longevity and negligible senescence rely on unique mechanisms to promote long-term maintenance of tissue homeostasis and physiological function while avoiding degenerative and neoplastic diseases. Understanding these mechanisms can reveal effective strategies to achieve longevity and healthy aging.

Comparative genomics between long-lived and short-lived species is a powerful approach to understand the evolution of longevity and enables unbiased discovery of genes and pathways that regulate lifespan. This approach has been used to identify molecular signatures related to longevity and has uncovered both shared and distinct strategies to modulate aging and disease resistance. Sea urchins represent a promising group of organisms to advance our understanding of lifespan determination and healthy aging. There are approximately 1,000 extant sea urchin species that exhibit a wide range of lifespans, including species with exceptional longevity and negligible senescence.

Life history data indicates that the red sea urchin, Mesocentrotus franciscanus, is one of the Earth's longest-living animals. It is reported to live more than 100 years and shows negligible senescence as defined by indeterminate growth, life-long reproduction, and no age-associated increase in mortality rate or increased incidence of disease, including no known cases of cancer. Negligible senescence has also been reported for other sea urchin species despite a wide range of lifespans. This includes the variegated sea urchin, Lytechinus variegatus, which is reported to live 3-4 years, the painted sea urchin, Lytechinus pictus, reported to live 5-7 years, and the purple sea urchin, Strongylocentrotus purpuratus, reported to live longer than 50 years.

Studies to date, conducted within the framework of known theories of aging, have demonstrated that both short-lived and long-lived sea urchin species lack many hallmarks of aging. Sea urchins maintain telomere length, antioxidant and proteasome enzyme activities, and regenerative capacity, and exhibit little accumulation of oxidative cellular damage with age. Gene expression studies using tissues of long-lived species indicate that key cellular pathways involved in protein homeostasis, tissue regeneration, and neurological function are maintained with age. Although genomes have been assembled for several sea urchin species, including S. purpuratus, L. variegatus, and L. pictus, to date no high-quality genome has become available for the long-lived red sea urchin M. franciscanus. Here we report a chromosome-level assembly for the red sea urchin genome. Targeted analysis of this genome and comparisons between long- and short-lived species sheds light on the molecular, cellular, and systemic mechanisms that promote longevity and negligible senescence.