# Calorie Restriction Effects on Aging, Learning Performance, and Transcription in Aged Aplysia californica

## TL;DR

Calorie restriction in sea slugs helps maintain cognitive abilities with age, unlike unrestricted feeding.

## Contribution

The study reveals how calorie restriction delays aging effects on learning in Aplysia californica.

## Key findings

- CR animals maintained cognitive performance in aged sea slugs, unlike AL animals.
- CR diet led to transcriptional changes linked to memory consolidation and neuronal function.
- Gene expression in CR animals showed enrichment in processes like protein kinase C binding and microtubule severing.

## Abstract

Along with increasing an animal's lifespan, calorie restriction (CR) is shown to improve an animal's cognition. To elucidate the molecular differences that accompany CR that may benefit cognition, sibling
Aplysia californica
were reared on either an ad‐lib (AL) or CR diet. Siblings from each diet were trained in two behaviors, learning food is inedible (LFI) and habituation of the tail withdrawal reflex (TWR), at two time points along their lifespans: younger animals at training time 1 (TT1) and aged siblings at training time 2 (TT2). In analysis by diet, TT2 CR animals' learning performance was on par with their TT1 CR siblings in both paradigms, illustrating a maintenance of cognition in age. Meanwhile, TT2 AL animals performed worse than TT1 AL siblings in habituation but better in LFI, illustrating the lack of cognitive maintenance in age. RNA sequencing was performed on part of the buccal ganglia that houses many of the neurons involved in LFI. Gene expression results implied morphological changes occurring within the motor and interneurons of the buccal ganglia after learning in LFI. These neurons showed enrichment of protein kinase C binding (GO:0005080), cadherin binding (GO:0045296), and microtubule severing ATPase activity (GO:0008568) as well as neuroactive ligand‐receptor interaction (ko04080) and valine, leucine and isoleucine biosynthesis (ko00290) all of which have been implicated to assist in memory consolidation and reconsolidation.

Buccal ganglia inter‐ and motoneuronal transcriptional changes were investigated after learning food is inedible (LFI) in
Aplysia californica
reared on different diets at two ages. Those reared on calorie restriction showed delayed signs of aging and maintained their performance in LFI when aged while those reared on ad‐lib did not.