To help aging populations, classify organismal senescence

Calimport, Stuart R. G.; Bentley, Barry L; Stewart, Claire E.; Pawelec, Graham; Scuteri, Angelo; Vinciguerra, Manlio; Slack, Cathy; Chen, Danica; Harries, Lorna W.; Marchant, Gary E.; Fleming, G. Alexander; Conboy, Michael J.; Antebi, Adam; Small, Gary W.; Gil, Jesús; Lakatta, Edward G.; Richardson, Arlan; Rosen, Clifford J.; Nikolich, Karoly; Wyss‐Coray, Tony; Steinman, Lawrence; Montine, Thomas J.; Magalhães, João Pedro de; Campisi, Judith; Church, George M.

doi:10.1126/science.aay7319

Cited by 50 publications

(30 citation statements)

References 13 publications

(23 reference statements)

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“…might help identify senescent cells implicated in tissue pathology. This information might be particularly valuable given the growing recognition that disease diagnosis, etiology, progression, and treatment vary in older populations [42].…”

Section: Agingmentioning

confidence: 99%

Survey of senescent cell markers with age in human tissues

Idda

McClusky

Lodde

et al. 2020

Aging

110

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Cellular senescence, triggered by sublethal damage, is characterized by indefinite growth arrest, altered gene expression patterns, and a senescence-associated secretory phenotype. While the accumulation of senescent cells during aging decreases tissue function and promotes many age-related diseases, at present there is no universal marker to detect senescent cells in tissues. Cyclin-dependent kinase inhibitors 2A (p16/CDKN2A) and 1A (p21/CDKN1A) can identify senescent cells, but few studies have examined the numbers of cells expressing these markers in different organs as a function of age. Here, we investigated systematically p16-and p21-positive cells in tissue arrays designed to include normal organs from persons across a broad spectrum of ages. Increased numbers of p21-positive and p16-positive cells with donor age were found in skin (epidermis), pancreas, and kidney, while p16-expressing cells increased in brain cortex, liver, spleen and intestine (colon), and p21-expressing cells increased in skin (dermis). The numbers of cells expressing p16 or p21 in lung did not change with age, and muscle did not appear to have p21-or p16positive cells. In summary, different organs display different levels of the senescent proteins p16 and p21 as a function of age across the human life span.

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Section: Agingmentioning

confidence: 99%

Survey of senescent cell markers with age in human tissues

Idda

McClusky

Lodde

et al. 2020

Aging

110

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show abstract

“…Aging is a complex, multifactorial process [1] that leads to loss of function and is the primary risk factor for major human pathologies including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases [1,2]. Although there is still much debate in the scientific community, proposals have been made to classify aging as a disease in order to develop therapeutic strategies to prevent or delay the onset of age-related illnessess [3][4][5]. Increasing frailty with age leads to an increased risk of many diseases.…”

Section: Introductionmentioning

confidence: 99%

Geroprotective and senoremediative strategies to reduce the comorbidity, infection rates, severity, and lethality in gerophilic and gerolavic infections

Zhavoronkov

2020

Aging

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The recently identified SARS-CoV-2 betacoronavirus responsible for the COVID-19 pandemic has uncovered the age-associated vulnerability in the burden of disease and put aging research in the spotlight. The limited data available indicates that COVID-19 should be referred to as a gerolavic (from Greek, géros "old man" and epilavís, "harmful") infection because the infection rates, severity, and lethality are substantially higher in the population aged 60 and older. This is primarily due to comorbidity but may be partially due to immunosenescence, decreased immune function in the elderly, and general loss of function, fitness, and increased frailty associated with aging. Immunosenescence is a major factor affecting vaccination response, as well as the severity and lethality of infectious diseases. While vaccination reduces infection rates, and therapeutic interventions reduce the severity and lethality of infections, these interventions have limitations. Previous studies showed that postulated geroprotectors, such as sirolimus (rapamycin) and its close derivative rapalog everolimus (RAD001), decreased infection rates in a small sample of elderly patients. This article presents a review of the limited literature available on geroprotective and senoremediative interventions that may be investigated to decrease the disease burden of gerolavic infections. This article also highlights a need for rigorous clinical validation of deep aging clocks as surrogate markers of biological age. These could be used to assess the need for, and efficacy of, geroprotective and senoremediative interventions and provide better protection for elderly populations from gerolavic infections. This article does not represent medical advice and the medications described are not yet licensed or recommended as immune system boosters, as they have not undergone clinical evaluation for this purpose.

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“…Comprehensive and systematic classification and staging of organ and tissue senescence, as well as pathologic atrophy, remodeling, calcification, and metabolic dysfunction, are urgently needed; this was recently proposed by a working group of prominent aging researchers. [ 50 ] Scoring systems may facilitate the development of personalized treatment recommendation, such as senolytic interventions acting on senescing tissues, or other therapies that take into account organ‐specific disease staging differentials.…”

Section: Molecular and Cellular Biomarkersmentioning

confidence: 99%

Aging Biomarkers: From Functional Tests to Multi‐Omics Approaches

Kudryashova¹,

Burka²,

Kulaga

et al. 2020

Proteomics

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Aging results in various deleterious changes in the human body that may lead to loss of function and the manifestation of chronic diseases. While diseases can generally be reliably diagnosed, the aging process itself requires more sophisticated approaches to evaluate its progression. Numerous attempts have been made to establish biomarkers to quantify human aging at the cellular, tissue, and organismal level. Here, an up‐to‐date overview of biomarkers related to human aging with an emphasis on biomarkers that take into account different mechanisms of aging between individuals is provided. Classical discrete molecular and non‐molecular biomarkers handpicked by researches on the base of their strong correlation with age, as well as emerging omics‐based biomarkers, are discussed and potential future directions and developments in the field of aging assessment are outlined.

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To help aging populations, classify organismal senescence

Abstract: Comprehensive disease classification and staging is required to address unmet needs of aging populations

Cited by 50 publications

References 13 publications

Survey of senescent cell markers with age in human tissues

Survey of senescent cell markers with age in human tissues

Geroprotective and senoremediative strategies to reduce the comorbidity, infection rates, severity, and lethality in gerophilic and gerolavic infections

Aging Biomarkers: From Functional Tests to Multi‐Omics Approaches

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