Telomere Length as a Marker of Biological Age: State-of-the-Art, Open Issues, and Future Perspectives

Vaiserman, Alexander; Krasnienkov, Dmytro

doi:10.3389/fgene.2020.630186

Cited by 262 publications

(211 citation statements)

References 182 publications

(233 reference statements)

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“…Aging is associated with telomere shortening and damage in several tissues (Vaiserman & Krasnienkov, 2021) (Demanelis et al, 2020) (Fumagalli et al, 2012) (Hewitt et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging

Sepe

Rossiello

Cancila

et al. 2021

Preprint

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is known to be more common in the elderly, who show also more severe symptoms and a higher risk of hospitalization and death. Here we show that the expression of the Angiotensin Converting Enzyme 2 (ACE2), the SARS-CoV2 cell receptor, increases during aging in mouse and human lungs, and following telomere shortening or dysfunction in mammalian cells and in mouse models. This increase is regulated at the transcription level, and Ace2 promoter activity is DNA damage response (DDR)-dependent. Indeed, ATM inhibition or the selective inhibition of telomeric DDR, through the use of antisense oligonucleotides, prevents Ace2 upregulation following telomere damage, in cultured cells and in mice.We propose that during aging telomeric shortening, by triggering DDR activation, causes the upregulation of ACE2, the SARS-CoV2 cell receptor, thus making the elderly likely more susceptible to the infection.

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“…Aging is associated with telomere shortening and damage in several tissues (Vaiserman & Krasnienkov, 2021) (Demanelis et al, 2020) (Fumagalli et al, 2012) (Hewitt et al, 2012).…”

Section: Resultsmentioning

confidence: 99%

DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging

Sepe

Rossiello

Cancila

et al. 2021

Preprint

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“…Short telomeres are associated with several age-related diseases: coronary artery disease, Alzheimer's disease, chronic obstructive disease, and osteoporosis (reviewed in [134,135]). Shorter telomeres are also observed in some cancers (reviewed in [136]).…”

Section: Discussionmentioning

confidence: 99%

Potential of Telomerase in Age-Related Macular Degeneration—Involvement of Senescence, DNA Damage Response and Autophagy and a Key Role of PGC-1α

Błasiak

Szczepańska

Fila

et al. 2021

IJMS

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Age-related macular degeneration (AMD), the main cause of vision loss in the elderly, is associated with oxidation in the retina cells promoting telomere attrition. Activation of telomerase was reported to improve macular functions in AMD patients. The catalytic subunit of human telomerase (hTERT) may directly interact with proteins important for senescence, DNA damage response, and autophagy, which are impaired in AMD. hTERT interaction with mTORC1 (mTOR (mechanistic target of rapamycin) complex 1) and PINK1 (PTEN-induced kinase 1) activates macroautophagy and mitophagy, respectively, and removes cellular debris accumulated over AMD progression. Ectopic expression of telomerase in retinal pigment epithelium (RPE) cells lengthened telomeres, reduced senescence, and extended their lifespan. These effects provide evidence for the potential of telomerase in AMD therapy. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may be involved in AMD pathogenesis through decreasing oxidative stress and senescence, regulation of vascular endothelial growth factor (VEGF), and improving autophagy. PGC-1α and TERT form an inhibitory positive feedback loop. In conclusion, telomerase activation and its ectopic expression in RPE cells, as well as controlled clinical trials on the effects of telomerase activation in AMD patients, are justified and should be assisted by PGC-1α modulators to increase the therapeutic potential of telomerase in AMD.

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“…Obviously, stress exposure has multiple effects on physiology, and our data support the proposal that telomere dynamics might represent an integrative measure of the impact of an individual's experience on its overall biological state. [35][36][37] However, it was only in old age that telomere length was predictive of mortality risk, with telomere length reached by 36 months predicting the probability of dying within the following year. This suggests that there could be a critical telomere length below which the expected association with mortality risk emerges and above which it disappears.…”

Section: Discussionmentioning

confidence: 99%

Repeated exposure to challenging environmental conditions influences telomere dynamics across adult life as predicted by changes in mortality risk

et al. 2021

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Telomere Length as a Marker of Biological Age: State-of-the-Art, Open Issues, and Future Perspectives

Cited by 262 publications

References 182 publications

DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging

DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging

Potential of Telomerase in Age-Related Macular Degeneration—Involvement of Senescence, DNA Damage Response and Autophagy and a Key Role of PGC-1α

Repeated exposure to challenging environmental conditions influences telomere dynamics across adult life as predicted by changes in mortality risk

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