Canonical and extra‐telomeric functions of telomerase: Implications for healthy ageing conferred by endurance training

Abstract

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Extended longevity of termite kings and queens is accompanied by extranuclear localization of telomerase in somatic organs and caste-specific expression of its isoforms

“…All above observations point at the extranuclear localization of a specific TERT isoform in somatic tissues of different termite castes, which is particularly enriched in the soma of long- lived reproductives and may be linked with their longevity via an unknown non-canonical function independent of telomere maintenance. Within the growing list of non-canonical roles attributed to hTERT and telomerase in humans, several functions are accompanied by active telomerase export from the nucleus upon oxidative stress and participation of TERT in protection against oxidative damage (reviewed, e.g., in Cong & Shay, 2008; Ding et al ., 2013; Saretzki, 2014; Romaniuk et al ., 2019; Ségal-Bendirdjian & Geli, 2019; Zheng et al ., 2019; Smith et al ., 2022; Denham, 2023). It is mostly manifested in mitochondria by reducing the levels of reactive oxygen species, protecting mtDNA from oxidative damage and enhancing the efficiency of respiratory chain.…”

Nurturing longevity through natural compounds: Where do we stand, and where do we go?

“…As a result, 10 years after their appearance, the understanding of the molecular mechanisms underlying aging has been expanded, and many significant advancements have been made in regard to uncovering the secrets behind aging and its reversal, along with the investigation of various pro-longevity therapies and interventions (Lopez-Otin et al, 2013, 2023, including the use of plant-derived natural compounds (Table 1).…”

“…The assembly of telomerase occurs within specialized subnuclear structures called Cajal bodies, and its proper trafficking to telomeres is facilitated by the telomerase Cajal body protein 1 and TPP1 proteins (L. Chen et al, 2018;Vogan et al, 2016). Composed of the telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC) genes and their associated dyskerin complex (Figure 2), telomerase catalyzes the addition of telomeric DNA to the ends of chromosomes, countering the natural shortening of telomeres that occurs with each cell division (Denham, 2023) F I G U R E 2 Mechanistic molecular pathways and subcellular structures involved in the aging processes through regulation of genome, epigenome, and transcriptome levels that could be employed as targets for longevity interventions. AKT, protein kinase B; AMPK, adenosine monophosphate-activated protein kinase; ATM, ataxia telangiectasia mutated; ATR, ataxia-telangiectasia mutated and rad3-related; BER, base excision repair; BRCA1/2, Breast Cancer gene 1/2; CHK1/2, checkpoint kinase 1/2; ERK, extracellular signal-regulated kinase; ERCC1-XPF, excision repair cross complementing 1 protein-xeroderma pigmentosum group F; FOXO, Forkhead box class O proteins; HR, homologous recombination; IRF(R), insulin-like growth factor (receptor); IR, insulin receptor; IRS, insulin receptor substrate; MEK, mitogen-activated protein kinase/ERK kinase; mTOR, mammalian target of rapamycin; NER, nucleotide excision repair; NHEJ, non-homologous end joining; OSK (Oct4, Klf4, Sox2), Yamanaka factors; PARP1/2, poly (ADP-ribose) polymerase; PI3K, phosphatidylinositol 3-kinase; POT1, protection of telomere 1; RAP1, Ras-proximate-1; STK17A, serine/threonine kinase 17a; TERC, telomerase RNA component; TERT, telomerase reverse transcriptase; TIN2, TERF1-interacting nuclear factor 2; TRF1/2, telomeric repeat binding factor 1/2; TPP1, tripeptidyl-peptidase 1.…”

“…The present review aimed to critically evaluate the published data on the modulation of the aging hallmarks to promote longevity and overall well-being over the past 10 years. Here, we define the original nine hallmarks as "old" ones, given their presence in the aging field for over a decade, and interpret the additional ones that were recently introduced as "new" (Lopez-Otin et al, 2013, 2023. The following keyword combinations were used to retrieve the relevant articles from scientific databases: "natural compounds," "phytochemicals," "ageing," "longevity," "lifespan," and "healthspan."…”

Telomere shortening induces aging-associated phenotypes in hiPSC-derived neurons and astrocytes

“…Consequently, short telomeres are considered one of the primary hallmarks of aging, as they lead to aging hallmarks including genomic instability, cellular senescence, and loss of regenerative capacity (López-Otín et al 2023 ). Cell and animal models with genetic modifications or absence of telomerase activity have provided direct evidence for the role of telomerase in the maintenance of telomeres and its contribution to biological aging (Denham 2023 ). Moreover, telomeropathies, arising from mutations in genes responsible for telomere maintenance, manifest as premature aging syndromes (Vieri et al 2021 ).…”