The great pond snail (Lymnaea stagnalis) has been used for neurobiological research at the ELKH Balaton Limnological Research Institute for more than 30 years. Partly supported by the National Brain Research Program (NAP), the Ecophysiological and Environmental Toxicological Research Group has identified new homolog sequences in Lymnaea to vertebrate genes involved in aging. The latest findings, as well as an overview of the results originating from age-related studies utilizing Lymnaea, have been published in the prestigious The Journals of Gerontology: Series A, in collaboration with researchers at the University of Sussex (Brighton, UK).

In modern society, the general increase of life span supported by rapid advances in medical interventions also resulted in a growing number of people being affected by age-related changes to the nervous system, such as decreased learning and memory, and diseases and conditions such as mild cognitive impairment and dementia. This can have a dramatic impact on quality of life, and can also impose emotional and financial burdens not just on the affected individuals but also their carers, relatives and the society as a whole. As a result, there is a great social and economic need to better understand the mechanisms underlying these neurophysiological processes leading to therapeutic interventions.

Researchers are looking for possible solutions to slow down or even reverse the loss of memory associated with aging. However, relatively little information is currently available on the key molecules, signaling pathways, and cellular changes responsible for aging and age-related memory impairment.

Due to the complexity of their nervous systems, the study of aging processes in vertebrates is not an easy task at the level of neural circuits and individually identified neurons. As a result, aging research relies heavily on invertebrate model organisms. One such invertebrate model animal is the great pond snail (Lymnaea stagnalis), which has been a well-known and popular subject for aging and memory research for decades. The research team had previously studied the effect of PACAP protein and IGF-1 hormone on reversing aging in Lymnaea. The researchers then established that neural circuits can be re-programmed pharmacologically to rejuvenate old animals and to improve memory.

Although many age-related findings have been obtained for Lymnaea over the years at the level of neural circuits and associated behaviors, the underlying detailed molecular mechanisms had not yet been studied in the absence of sequences of evolutionarily conserved, relevant key molecules. To make this possible, the research team identified a number of evolutionarily conserved sequences in Lymnaea to genes that are associated with the aging of vertebrates or the development of human neurodegenerative diseases, such as Parkinson’s, Alzheimer’s, and Huntington’s disease. Thanks to the findings presented, the research group successfully won the tender of the New National Excellence Program (ÚNKP-20-3-II-PTE-888) and the Cooperative Doctoral Program (KDP-2020-1018493) implemented in 2020 with the support of NKFIH, so it can continue to model aging processes using Lymnaea.

The research team recently identified additional, previously unknown sequences in Lymnaea that are responsible for epigenetic modifications which also play a key role in vertebrate aging, providing the opportunity for a broad-based study of molecular and cellular changes during aging.

The review article highlights that the results of the “Lymnaea aging model” confirmed, among other things, that several consistent, evolutionarily conserved behavioral, anatomical, and physiological processes take place in different invertebrate and vertebrate species (e.g., declined implicit learning and motor functions, reduced neural arborization).

In order to continue the research, the research group also submitted an FK-OTKA application this year entitled “Cellular and molecular mechanisms of age-related changes in a defined neuronal network encoding associative memory”, in which the researchers aim to slow down age-related memory impairment by genetically manipulating evolutionarily conserved genes – klotho [#MT153186], huntingtin [#MT153189], presenilin [#MT153195], RbAp48/RBBP4 [#QNG40052] – that are assumed to play a key role in learning processes (e.g., through NMDA receptors).