Proteasome Modulation: A Way to Delay Aging?

Pharmacological intervention in a transgenic mouse model improves Alzheimer's-associated pathological phenotype: Involvement of proteasome activation

“…6A , i ). As proteasome can be activated by different modes of function [ 68 ], next we examined the compounds’ effects on the transcriptional activation of its subunits. Treatment with 18α-GA and 18α-GA + n-3FA but not with n-3FA alone enhanced the protein levels of the catalytic β5 proteasome subunit to similar rates ( Fig.…”

Healthspan improvement and anti-aggregation effects induced by a marine-derived structural proteasome activator

“…We and other research groups have reported that proteasome activation delays cellular senescence [ 9 , 14 , 18 ]. Given the proteasome activating properties of DBTO ( 1 ), we sought to investigate its effects on the progression of senescence in human primary embryonic fibroblasts.…”

“…Thus, it is not surprising that an age-related impairment of the proteasome function in both in vitro and in vivo aging models (where redox status is altered) has been revealed. As aging progresses, the proteasome content and function diminish [ 9 ]. In contrast, cultured fibroblasts from healthy centenarians maintained their proteasomes active compared to cultures from old donors [ 10 ], thus potentially indicating the importance of preserved functional proteasomes for a successful aging process.…”

The role of cycloastragenol at the intersection of NRF2/ARE, telomerase, and proteasome activity

“…Moreover, hTERT was determined to bind to multiple proteasome subunits and promote 26S proteasome assembly, which indicates another non-canonical function for hTERT that is independent of its telomere-regulatory function [80]. Studies toward the discovery of proteasome activators have been reported several natural and synthetic small compounds that stimulate proteasomal activity [81]. Although there are several studies regarding proteasome activation of triterpenoids such as Betulinic acid [82], 18α-GA [25], and Hederagenin [25], no study has been reported to determine the effects of CA on the proteasomal activity.…”