Abstract
Frailty is a geriatric syndrome associated with both locomotor and cognitive decline, typically linked to chronic systemic inflammation, i.e., inflammaging. In the current study, we investigated the effect of a two-month oral supplementation with standardized extracts of H. erinaceus, containing a known amount of Erinacine A, Hericenone C, Hericenone D, and L-ergothioneine, on locomotor frailty and cerebellum of aged mice. Locomotor performances were monitored comparing healthy aging and frail mice. Cerebellar volume and cytoarchitecture, together with inflammatory and oxidative stress pathways, were assessed focusing on senescent frail animals. H. erinaceus partially recovered the aged-related decline of locomotor performances. Histopathological analyses paralleled by immunocytochemical evaluation of specific molecules strengthened the neuroprotective role of H. erinaceus able to ameliorate cerebellar alterations, i.e., milder volume reduction, slighter molecular layer thickness decrease and minor percentage of shrunken Purkinje neurons, also diminishing inflammation and oxidative stress in frail mice while increasing a key longevity regulator and a neuroprotective molecule. Thus, our present findings demonstrated the efficacy of a non-pharmacological approach, based on the dietary supplementation using H. erinaceus extract, which represent a promising adjuvant therapy to be associated with conventional geriatric treatments.
Highlights
Numerous findings further implicate the cerebellum in motor declines in older adults, supporting the idea that cerebellar-prefrontal circuits may be especially important for motor and cognitive performance in older age
With regard to oxidative stress pathway, our findings demonstrated a marked reduction of both iNOS and Cyclooxygenase 2 (COX2) immunopositivity in He1 mice only, paralleled by a concurrent slighter, but even significant, decrease of superoxide dismutase-1 (SOD1) immunoreactivity
Our present results revealed a significant increase of vascular endothelial growth factor (VEGF) expression levels, mainly localized in Purkinje cells soma and mossy fibers rosettes, in He1 treated mice only, evaluated in terms of both cell frequency and optical density (OD), while a complete lack of immunoreactivity was evidenced at blood vessels level
Summary
Aging is a universal process characterized by a gradual decline in physical and cognitive functions. A variety of changes occur, including brain atrophy, oxidative stress, and reduced antioxidant mechanisms, contributing to impairment of cognitive and locomotor performances [1]. The term frailty was proposed to describe a multisystemic impairment scenario, which negatively affects the health of an elderly individual, contributing to aggravate a clinical condition that is often already compromised. The World Health Organization (WHO) recognized frailty as an increasingly widespread syndrome that should be prevented, reversed, or at least mitigated to improve the quality of life in the elderly [2]
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