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Immunosuppression commonly disrupts the homeostasis of mutated normal skin, leading to widespread skin dysplasia and field cancerization. However, the immune system's role in maintaining the normal state of mutated tissues remains uncertain. Herein, we demonstrate that T cell immunity to cutaneotropic papillomaviruses promotes the homeostasis of ultraviolet radiation-damaged skin. Mouse papillomavirus (MmuPV1) colonization blocks the expansion of mutant p53 clones in the epidermis in a CD8^(+) T...

This concise review provides new perspectives on systemic reduction of tissue aging by comparing different strategies, such as heterochronic parabiosis, injections of young blood plasma, neutral blood exchange (NBE) and therapeutic plasma exchange (TPE). Unlike previous literature that primarily discusses the need for young blood factors, we emphasize the potential of diluting age-elevated proteins as the way to re-calibrate systemic proteome to its younger state without donor blood....

CONCLUSIONS: HGS asymmetry and weakness were associated with an increased risk of composite and individual domain IC impairment. Assessing and maintaining HGS symmetry and strength may have implications for the early identification of individuals at risk for IC impairment and the prevention of related adverse health outcomes.

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Substantial shifts in reproductive behaviors have recently taken place in many high-income countries including earlier age at menarche, advanced age at childbearing, rising childlessness and a lower number of children. As reproduction shifts to later ages, genetic factors may become increasingly important. Although monogenic genetic effects are known, the genetics underlying human reproductive traits are complex, with both causal effects and statistical bias often confounded by socioeconomic...

Sex hormone signaling declines during aging, from early midlife through menopause, as a consequence of reduced circulating estrogens and decreased receptiveness to these hormones in target tissues. Estrogens preserve energy homeostasis and promote metabolic health via coordinated and simultaneous effects throughout the brain and body. Age-associated loss of estrogen production during menopause has been implicated in a higher risk for metabolic diseases and increased mortality. However, it...

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People today are choosing to have children later in life, often in their thirties and forties, when their fertility is in decline. We sought to identify and compile effective methods for improving either male or female fertility in this context of advanced reproductive age. We found few clinical studies with strong evidence for therapeutics that mitigate reproductive aging or extend fertility; however, this Perspective summarizes the range of emerging experimental strategies under development....

The female reproductive axis is one of the first organ systems to age, which has consequences for fertility and overall health. Here, we provide a comprehensive overview of the biological process of female reproductive aging across reproductive organs, tissues and cells based on research with widely used physiologic aging mouse models, and describe the mechanisms that underpin these phenotypes. Overall, aging is associated with dysregulation of the hypothalamic-pituitary-ovarian axis,...

Reproductive aging, spanning an age-related functional decline in the female and male reproductive systems, compromises fertility and leads to a range of health complications. In this Perspective, we first introduce a comprehensive framework for biomarkers applicable in clinical settings and discuss the existing repertoire of biomarkers used in practice. These encompass functional, imaging-based and biofluid-based biomarkers, all of which reflect the physiological characteristics of reproductive...

Ovarian aging is characterized by declines in follicular reserve and the emergence of mitochondrial dysfunction, reactive oxygen species production, inflammation, and fibrosis, which eventually results in menopause. Menopause is associated with increased systemic aging and the development of numerous comorbidities; therefore, the attenuation of ovarian aging could also delay systemic aging processes in women. Recent work has established that the anti-diabetic drug Canagliflozin (Cana), a...

Caloric restriction (CR) slows biological aging and prolongs healthy lifespan in model organisms. Findings from the CALERIE randomized, controlled trial of long-term CR in healthy, nonobese humans broadly supports a similar pattern of effects in humans. To expand our understanding of the molecular pathways and biological processes underpinning CR effects in humans, we generated a series of genomic datasets from stored biospecimens collected from n = 218 participants during the trial. These data...

Organellar homeostasis and crosstalks within a cell have emerged as essential regulatory and determining factors for the survival and functions of cells. In response to various stimuli, cells can activate the organellar quality control systems (QCS) to maintain homeostasis. Numerous studies have demonstrated that dysfunction of QCS can lead to various aging-related diseases such as neurodegenerative, pulmonary, cardiometabolic diseases and cancers. However, the interplay between QCS and their...