Common chronic diseases represent the greatest driver of rising healthcare costs, as well as declining function, independence, and quality of life. Geroscience‐guided approaches seek to delay the ...onset and progression of multiple chronic conditions by targeting fundamental biological pathways of aging. This approach is more likely to improve overall health and function in old age than treating individual diseases, by addressing aging the largest and mostly ignored risk factor for the leading causes of morbidity in older adults. Nevertheless, challenges in repurposing existing and moving newly discovered interventions from the bench to clinical care have impeded the progress of this potentially transformational paradigm shift. In this article, we propose the creation of a standardized process for evaluating FDA‐approved medications for their geroscience potential. Criteria for systematically evaluating the existing literature that spans from animal models to human studies will permit the prioritization of efforts and financial investments for translating geroscience and allow immediate progress on the design of the next Targeting Aging with MEtformin (TAME)‐like study involving such candidate gerotherapeutics.
Geroscience‐guided approaches seek to delay the onset and progression of chronic conditions by targeting the pathways of aging. This approach is likely to improve overall health in old age by addressing aging—the largest risk factor for the leading causes of morbidity. Here, we propose the creation of a standardized process for evaluating FDA‐approved drugs for their geroscience potential, permitting the prioritization of efforts and investments for translating geroscience discoveries.
Abstract
Background
Hospitalized COVID-19 patients tend to be older and frequently have hypertension, diabetes, or coronary heart disease, but whether these comorbidities are true risk factors (ie, ...more common than in the general older population) is unclear. We estimated associations between preexisting diagnoses and hospitalized COVID-19 alone or with mortality, in a large community cohort.
Methods
UK Biobank (England) participants with baseline assessment 2006–2010, followed in hospital discharge records to 2017 and death records to 2020. Demographic and preexisting common diagnoses association tested with hospitalized laboratory-confirmed COVID-19 (March 16 to April 26, 2020), alone or with mortality, in logistic models.
Results
Of 269 070 participants aged older than 65, 507 (0.2%) became COVID-19 hospital inpatients, of which 141 (27.8%) died. Common comorbidities in hospitalized inpatients were hypertension (59.6%), history of fall or fragility fractures (29.4%), coronary heart disease (21.5%), type 2 diabetes (type 2, 19. 9%), and asthma (17.6%). However, in models adjusted for comorbidities, age group, sex, ethnicity, and education, preexisting diagnoses of dementia, type 2 diabetes, chronic obstructive pulmonary disease, pneumonia, depression, atrial fibrillation, and hypertension emerged as independent risk factors for COVID-19 hospitalization, the first 5 remaining statistically significant for related mortality. Chronic kidney disease and asthma were risk factors for COVID-19 hospitalization in women but not men.
Conclusions
There are specific high-risk preexisting comorbidities for COVID-19 hospitalization and related deaths in community-based older men and women. These results do not support simple age-based targeting of the older population to prevent severe COVID-19 infections.
Senescent cells are highly associated with aging and pathological conditions and could be targeted to slow the aging process. One commonly used marker to examine senescent cells in vivo is p16, which ...has led to important discoveries. Recent studies have also described new senescence markers beyond p16 and have highlighted the importance of investigating senescence heterogeneity in cell types and tissues. With the development of high-throughput technologies, such as single-cell RNA-seq and single-nucleus RNA-seq, we can examine senescent cells at the single-cell level and potentially uncover new markers. This review emphasizes that there is an urgent need to investigate senescence heterogeneity and discuss how this could be accomplished by using advanced technologies and sequencing datasets.
Currently, senescent cells do not have a known gold standard genetic marker.Single cell RNA-seq and single-nucleus RNA-seq have emerged as powerful methods for investigating senescence heterogeneity.It is unknown what cell populations are being targeted by senolytics in vivo.Gaining a greater understanding of senescent cell heterogeneity can have large clinical implications and improve patient treatment.
Differences in immune function and responses contribute to health- and life-span disparities between sexes. However, the role of sex in immune system aging is not well understood. Here, we ...characterize peripheral blood mononuclear cells from 172 healthy adults 22-93 years of age using ATAC-seq, RNA-seq, and flow cytometry. These data reveal a shared epigenomic signature of aging including declining naïve T cell and increasing monocyte and cytotoxic cell functions. These changes are greater in magnitude in men and accompanied by a male-specific decline in B-cell specific loci. Age-related epigenomic changes first spike around late-thirties with similar timing and magnitude between sexes, whereas the second spike is earlier and stronger in men. Unexpectedly, genomic differences between sexes increase after age 65, with men having higher innate and pro-inflammatory activity and lower adaptive activity. Impact of age and sex on immune phenotypes can be visualized at https://immune-aging.jax.org to provide insights into future studies.