Telomere elongation in the gut extends zebrafish lifespan

Telomere shortening is a hallmark of aging and is counteracted by telomerase. The gut is one of the earliest organs to exhibit short telomeres and tissue dysfunction during normal zebrafish aging. This is recapitulated in prematurely aged telomerase mutants (tert-/-). Here, we show that gut-specific telomerase activity in tert-/- zebrafish prevents premature aging. Induction of telomerase rescues gut senescence and low cell proliferation to wild-type levels, while restoring gut tissue integrity, inflammation, and age-dependent gut microbiota dysbiosis. Remarkably, averting gut dysfunction results in a systemic beneficial impact. Gut-specific telomerase activity rescues premature aging markers in remote organs, such as the reproductive (testes) and hematopoietic (kidney marrow) systems. Functionally, it also rescues age-dependent loss of male fertility and testes atrophy. Finally, we show that gut-specific telomerase activity increases the lifespan of telomerase mutants. Our work demonstrates that delaying telomere shortening in the gut is sufficient to systemically counteract aging in zebrafish.

The Impact of Exercise on Telomere Length, DNA Methylation and Metabolic Footprints

Aging as a major risk factor influences the probability of developing cancer, cardiovascular disease and diabetes, amongst others. The underlying mechanisms of disease are still not fully understood, but research suggests that delaying the aging process could ameliorate these pathologies. A key biological process in aging is cellular senescence which is associated with several stressors such as telomere shortening or enhanced DNA methylation. Telomere length as well as DNA methylation levels can be used as biological age predictors which are able to detect excessive acceleration or deceleration of aging. Analytical methods examining aging are often not suitable, expensive, time-consuming or require a high level of technical expertise. Therefore, research focusses on combining analytical methods which have the potential to simultaneously analyse epigenetic, genomic as well as metabolic changes.

Telomere Shortening and Its Association with Cell Dysfunction in Lung Diseases

Telomeres are localized at the end of chromosomes to provide genome stability; however, the telomere length tends to be shortened with each cell division inducing a progressive telomere shortening (TS). In addition to age, other factors, such as exposure to pollutants, diet, stress, and disruptions in the shelterin protein complex or genes associated with telomerase induce TS. This phenomenon favors cellular senescence and genotoxic stress, which increases the risk of the development and progression of lung diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, SARS-CoV-2 infection, and lung cancer. In an infectious environment, immune cells that exhibit TS are associated with severe lymphopenia and death, whereas in a noninfectious context, naïve T cells that exhibit TS are related to cancer progression and enhanced inflammatory processes. In this review, we discuss how TS modifies the function of the immune system cells, making them inefficient in maintaining homeostasis in the lung. Finally, we discuss the advances in drug and gene therapy for lung diseases where TS could be used as a target for future treatments.

Effect of Physical Activity, Smoking, and Sleep on Telomere Length: A Systematic Review of Observational and Intervention Studies

Aging is a risk factor for several pathologies, restricting one’s health span, and promoting chronic diseases (e.g., cardiovascular and neurodegenerative diseases), as well as cancer. Telomeres are regions of repetitive DNA located at chromosomal ends. Telomere length has been inversely associated with chronological age and has been considered, for a long time, a good biomarker of aging. Several lifestyle factors have been linked with telomere shortening or maintenance. However, the consistency of results is hampered by some methodological issues, including study design, sample size, measurement approaches, and population characteristics, among others. Therefore, we aimed to systematically review the current literature on the effects of three relevant lifestyle factors on telomere length in human adults: physical activity, smoking, and sleep. We conducted a qualitative systematic review of observational and intervention studies using the Preferred Reporting Item for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The systematic literature search covered articles published in MEDLINE and EMBASE databases (from 2010 to 2020). A total of 1400 studies were identified; 83 were included after quality control. Although fewer sedentary activities, optimal sleep habits, and non- or ex-smoker status have been associated with less telomere shortening, several methodological issues were detected, including the need for more targeted interventions and standardized protocols to better understand how physical activity and sleep can impact telomere length and aging. We discuss the main findings and current limitations to gain more insights into the influence of these lifestyle factors on the healthy aging process.

Early exposure to UV radiation causes telomere shortening and poorer condition later in life

Determining the contribution of elevated ultraviolet–B radiation (UVBR; 280 — 315 nm) to amphibian population declines is being hindered by a lack of knowledge about how different acute UVBR exposure regimes during early life history stages might affect post–metamorphic stages via long–term carryover effects. We acutely exposed tadpoles of the Australian green tree frog (Litoria caerulea) to a combination of different UVBR irradiances and doses in a multi–factorial experiment, and then reared them to metamorphosis in the absence of UVBR to assess carryover effects in subsequent juvenile frogs. Dose and irradiance of acute UVBR exposure influenced carryover effects into metamorphosis in somewhat opposing manners. Higher doses of UVBR exposure in larvae yielded improved rates of metamorphosis. However, exposure at a high irradiance resulted in frogs metamorphosing smaller in size and in poorer condition than frogs exposed to low and medium irradiance UVBR as larvae. We also demonstrate some of the first empirical evidence of UVBR-induced telomere shortening in vivo, which is one possible mechanism for life–history trade–offs impacting condition post-metamorphosis. These findings contribute to our understanding of how acute UVBR exposure regimes in early life affect later life–history stages, which has implications for how this stressor may shape population dynamics.

Prenatal thyroid hormones accelerate postnatal growth and telomere shortening in wild great tits

Early-life environment is known to affect later-life health and disease, which could be mediated by the early-life programming of telomere length, a key hallmark of ageing. According to the fetal programming of telomere biology hypothesis, variation in prenatal exposure to hormones is likely to influence telomere length. Yet the contribution of key metabolic hormones, i.e. thyroid hormones (THs), has been largely ignored. We recently showed that in contrast to predictions, exposure to elevated prenatal THs increased postnatal telomere length in wild collared flycatchers, but the generality of such effect, its underlying proximate mechanisms and consequences on survival have not been investigated. We therefore conducted a comprehensive study evaluating the impact of THs on potential drivers of telomere dynamics (growth, post-natal THs, mitochondria and oxidative stress), telomere length and medium-term survival using wild great tits as a model system. While prenatal THs did not significantly affect telomere length after hatching (i.e. day 7), they influenced postnatal telomere shortening (i.e. shorter telomeres at day 14 and the following winter) but not apparent survival. Circulating THs, mitochondrial density or oxidative stress biomarkers were not significantly influenced, whereas TH-supplemented group showed accelerated growth, which may explain the observed delayed effect on telomeres. We discuss several alternative hypotheses that may explain the contrast with our previous findings in flycatchers. Given that shorter telomeres in early life tend to be carried until adulthood and are often associated with decreased survival prospects, the effects of prenatal THs on telomeres may have long-lasting effects on senescence.

From climate warming to accelerated cellular ageing: an experimental study in wild birds

Climate change is increasing both the average ambient temperature and the frequency and severity of heat waves. While direct mortality induced by heat waves is increasingly reported, sub-lethal effects are also likely to impact wild populations. We hypothesized that accelerated ageing could be a cost of being exposed to higher ambient temperature, especially in early-life when thermoregulatory capacities are not fully developed. We tested this hypothesis in wild great tit (Parus major) by experimentally increasing nest box temperature by ca. 2 degrees during postnatal growth and measuring telomere length, a biomarker of cellular ageing predictive of survival prospects in many bird species. While increasing early-life temperature does not affect growth or survival to fledging, it accelerates telomere shortening and reduces medium-term survival from 34% to 19%. Heat-induced telomere shortening was not explained by oxidative stress, but more likely by an increase in energy demand (i.e. higher thyroid hormones levels, increased expression of glucocorticoid receptor, increased mitochondrial density) leading to a reduction in telomere maintenance mechanisms (i.e. decrease in the gene expression of telomerase and protective shelterin). Our results thus suggest that climate warming can affect ageing rate in wild birds, with potential impact on population dynamics and persistence.