Telomere shortening rate predicts species life span

Whittemore, Kurt; Vera, Elsa; Martínez‐Nevado, Eva; Sanpera, Carola; Blasco, Marı́a A.

doi:10.1073/pnas.1902452116

Cited by 294 publications

(247 citation statements)

References 46 publications

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“…The enzyme telomerase can replenish the lost telomeric DNA, a mechanism that plays a fundamental role in cancer growth, but there is no evidence that telomerase is a resilience mechanism for aging. Telomeres have been proposed to serve as a “molecular clock,” and short telomeres have been hypothesized to contribute to the aging process (Greider, ; Saretzki, ; Vera, Bernardes de Jesus, Foronda, Flores, & Blasco, ; Whittemore, Vera, Martinez‐Nevado, Sanpera, & Blasco, ). A 13‐year prospective study in the Baltimore Longitudinal Study of Aging reported that indeed, average telomere length shortens with aging, but the direction and magnitude of change are different in different circulating cells and extremely heterogeneous across individuals, with a substantial percentage of individuals showing average lengthening.…”

Section: Introductionmentioning

confidence: 99%

Measuring biological aging in humans: A quest

et al. 2019

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The global population of individuals over the age of 65 is growing at an unprecedented rate and is expected to reach 1.6 billion by 2050. Most older individuals are affected by multiple chronic diseases, leading to complex drug treatments and increased risk of physical and cognitive disability. Improving or preserving the health and quality of life of these individuals is challenging due to a lack of well‐established clinical guidelines. Physicians are often forced to engage in cycles of “trial and error” that are centered on palliative treatment of symptoms rather than the root cause, often resulting in dubious outcomes. Recently, geroscience challenged this view, proposing that the underlying biological mechanisms of aging are central to the global increase in susceptibility to disease and disability that occurs with aging. In fact, strong correlations have recently been revealed between health dimensions and phenotypes that are typical of aging, especially with autophagy, mitochondrial function, cellular senescence, and DNA methylation. Current research focuses on measuring the pace of aging to identify individuals who are “aging faster” to test and develop interventions that could prevent or delay the progression of multimorbidity and disability with aging. Understanding how the underlying biological mechanisms of aging connect to and impact longitudinal changes in health trajectories offers a unique opportunity to identify resilience mechanisms, their dynamic changes, and their impact on stress responses. Harnessing how to evoke and control resilience mechanisms in individuals with successful aging could lead to writing a new chapter in human medicine.

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Section: Introductionmentioning

confidence: 99%

Measuring biological aging in humans: A quest

et al. 2019

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“…Despite the number of upstream, independent variables, the mechanism of telomere shortening and changes in epigenetic expression is shared and provides a common diagnostic, prognostic, and therapeutic focal point. In AD, for example, data show telomere shortening in older glial cells 143 and correlations between glial (or other) telomere lengths and AD status [144][145][146][147][148][149][150] (as well as Parkinson disease 151,152 ) and lifespan, 153 as well as epigenetic changes in neurons. 154,155 Not surprisingly, 156 studies looking at inappropriate cells (such as peripheral leukocytes) 157,158 often find inclusive or misleading results.…”

Section: Upstream Variablesmentioning

confidence: 99%

A unified model of dementias and age‐related neurodegeneration

Fossel

2020

Alzheimer's & Dementia

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Those working with Alzheimer's and other dementias have been frustrated by the implacability of these diseases. Regardless of limited symptomatic treatment, 1 there are no proven disease-modifying interventions. Despite huge and growing costs of care, 2 a pipeline of candidate drugs, 3 >400 registered trials, 4 tens of thousands of patients, 5 billions of dollars in both US federal 6 and pharmaceutical company investment, 7,8 more than a century of clinical expertise, and thousands of professional careers, dozens of pharmaceutical and biotechnology firms have foundered and failed 9 in attempts to prevent, slow, or alter the course of the dementias.This article presents a novel model to explain the relationships between age-related neurodegenerative disorders (eg, dementias) and the underlying molecular mechanisms of the aging process. The hypothesis is prompted by the fact that accepted conceptual models have failed to yield effective interventions for Alzheimer's or other dementias. 10 This article is a specific response to the Alzheimer's & Dementia editorial of November 2015, 11 which called for a systemic re-evaluation of our current models and their ability to answer fundamental questions regarding complex brain disorders and their relationship to clinical dementia, as well as the failure to yield effective clinical interventions.The article is divided into three parts. The first part explores current models of age-related neurogenerative diseases. The second part proposes a specific model and details both its working and its implications.The third part applies the model to answering the 10 key questions proposed by the Alzheimer's & Dementia editorial. The intent is to provide a conceptual model that accords with known data and proposes a novel point of clinical intervention. The model is intended to provoke discussion and provide a point of departure, rather than to offer a complete and final model for age-related neurodegenerative disease. The value of any such model rests on the outcome of clinical trials, but the model offers potentially innovative pathways to such trials. Current dementia modelsAlthough there is no general explanation for the failure to identify an effective intervention, there is growing consensus that a major factor is the lack of a comprehensive model for the dementias. 12 Over the past century, 13 several models have attained varying degrees of acceptance.Such models generally assume (or imply) a predominant single cause of Alzheimer's disease (AD; Figure 1).Such models suggest that, although several factors may contribute to the pathology, most Alzheimer's pathology results from a single predominant cause, such as amyloid plaque. In Figure 1, A (the predominant cause) is the leading causal factor, whereas B, C, D, and E represent contributing (but less significant or even incidental) factors.Until recently, the foremost among such explanations has been amyloid (A ) theory, [14][15][16][17] in various iterations. Other candidates have been tau tangles, 18-20 mitochondrial dysfun...

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“…Telomeres represent a particularly fragile genomic location and tend to accumulate damage during aging. Also, they tend to shorten during chronological aging, and their rate of shortening is inversely related to longevity in mammals and birds [52]. Unprotected telomeres trigger a DNA damage response leading to cellular senescence [53], which can accelerate aging.…”

Section: Molecular Level Telomeresmentioning

confidence: 99%

Development and Longevity: Cellular and Molecular Determinants – A Mini-Review

2020

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Across species, development and longevity are tightly linked. We discuss the relevant literature and suggest that the root for this stringent relationship is the rate of development. The basis for the relationship between rate of development and longevity lies in adaptations that have occurred through evolution at multiple levels of biological complexity: organism, organ, cellular, and molecular. Thus, the analysis of the relationship is of interest for multiple fields of biology.

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Telomere shortening rate predicts species life span

Cited by 294 publications

References 46 publications

Measuring biological aging in humans: A quest

Measuring biological aging in humans: A quest

A unified model of dementias and age‐related neurodegeneration

Development and Longevity: Cellular and Molecular Determinants – A Mini-Review

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