Ageing, Neurodegeneration and the Endocannabinoid System

Area of Science:

• Neuroscience
• Pharmacology
• Gerontology

Background:

• The endocannabinoid system (ECS) plays crucial neuromodulatory roles throughout life, including in the central nervous system (CNS).
• While ECS functions are well-studied in development and adulthood, its role in senescence and aging brains remains less explored.
• Altered ECS activity in aged brains contributes to cognitive and motor impairments, with these changes intensifying in neurodegenerative conditions.

Purpose of the Study:

• To review subtle alterations in the ECS of the aging brain without pathology.
• To demonstrate how these changes mirror extreme alterations seen in pathological brain aging.
• To explore neuroprotective therapies targeting the ECS for neurodegenerative diseases.

Main Methods:

• Literature review synthesizing existing research on the ECS in aging and neurodegeneration.
• Analysis of studies investigating cannabinoid receptor (CB1, CB2) expression and signaling pathways.
• Examination of endocannabinoid-inactivating enzymes (FAAH, MAGL) in aging and disease contexts.

Main Results:

• Aging is associated with altered ECS activity, including CB1 receptor downregulation and increased endocannabinoid-inactivating enzymes.
• These alterations can exacerbate age-related cognitive and motor deficits.
• Conversely, elevated endocannabinoids and CB2 receptor upregulation may represent protective adaptations.

Conclusions:

• The ECS undergoes significant changes during brain aging, both in normal senescence and in neurodegenerative diseases.
• Pharmacological modulation of ECS targets offers a promising therapeutic avenue for combating age-related neurodegeneration.
• Developing effective neuroprotective treatments is critical given increasing global lifespans and the incidence of age-related disorders.