ws for a deeper understanding of the skin microbiome's role in health and disease. These results should be helpful in the design of longer-term intervention trials with microbiome-based skin care treatments. Dermal injection of chemically cross-linked hyaluronic acid (CL-HA) is a common procedure to smooth wrinkles and add fullness to the face. Due to its physical properties, CL-HA both fills space and exerts mechanical forces within the dermis. Dermal fibroblasts produce the collagen-rich extracellular matrix (ECM), which comprises the bulk of skin. Attachment to the ECM allows fibroblasts to achieve a stretched, morphology, which confers a functional phenotype that maintains collagen production. In aged/photoaged skin, collagen fibril fragmentation impairs fibroblast attachment, resulting in a collapsed morphology and reduced collagen production. This article describes investigations of the impact of CL-HA injection on fibroblast morphology and function in the aged/photoaged human skin. Fifty-three subjects, age 70 years or older, received a single injection of saline (vehicle control) and CL-HA (0.5 ml each) in separate adjacent skin sites on photodamaged forearm or sun-protected buttock skin. Full-thicknecing production of collagen by dermal fibroblasts. Deposition of mature collagen, which remains in the skin for decades, likely confers long-term benefits. Reduced collagen production in aged/photoaged skin is an adaptive response of fibroblasts to ECM fragmentation, rather than inherent cellular aging mechanisms. Facial aging is a multifactorial process governed by both intrinsic and extrinsic factors that impart a change to each component of the facial anatomy. Our understanding of the science of aging has evolved over the years. A recent and valuable addition to our understanding is the knowledge of both the superficial and deep facial fat compartments. The deep compartments provide structural support to the midface and the superficial fat compartments. Understanding the anatomy and the spectrum of their changes helps to tailor management options for facial rejuvenation. The authors present a review on facial aging as it relates to these fat compartments and provide a management algorithm based on the longitudinal changes seen during aging. Facial aging is a multifactorial process governed by both intrinsic and extrinsic factors that impart a change to each component of the facial anatomy. Our understanding of the science of aging has evolved over the years. A recent and valuable addition to our understanding is the knowledge of both the superficial and deep facial fat compartments. https://www.selleckchem.com/products/Nutlin-3.html The deep compartments provide structural support to the midface and the superficial fat compartments. Understanding the anatomy and the spectrum of their changes helps to tailor management options for facial rejuvenation. The authors present a review on facial aging as it relates to these fat compartments and provide a management algorithm based on the longitudinal changes seen during aging. The genetic basis of youthfulness is poorly understood. The aging of skin depends on both intrinsic factors and extrinsic factors. Intrinsic factors include personal genetics, and extrinsic factors include environmental exposure to solar radiation and pollution. We recently reported the critical role of the mitochondria in skin aging phenotypes wrinkle formation, hair graying, hair loss, and uneven skin pigmentation. This article focuses on molecular mechanisms, specifically mitochondrial mechanisms underlying skin aging. This contribution describes the development of an mitochondrial DNA depleter-repleter mouse model and its usefulness in developing strategies and identifying potential agents that can either prevent, slow, or mitigate skin aging, lentigines, and hair loss. The ongoing research efforts include the transplantation of young mitochondria to rejuvenate aging skin and hair to provide youthfulness in humans. The genetic basis of youthfulness is poorly understood. The aging of skin depends on both intrinsic factors and extrinsic factors. Intrinsic factors include personal genetics, and extrinsic factors include environmental exposure to solar radiation and pollution. We recently reported the critical role of the mitochondria in skin aging phenotypes wrinkle formation, hair graying, hair loss, and uneven skin pigmentation. This article focuses on molecular mechanisms, specifically mitochondrial mechanisms underlying skin aging. This contribution describes the development of an mitochondrial DNA depleter-repleter mouse model and its usefulness in developing strategies and identifying potential agents that can either prevent, slow, or mitigate skin aging, lentigines, and hair loss. The ongoing research efforts include the transplantation of young mitochondria to rejuvenate aging skin and hair to provide youthfulness in humans. Cellular senescence is a state of stable cell cycle arrest that has increasingly been linked with cellular, tissue, and organismal aging; targeted removal of senescent cells brings healthspan and lifespan benefits in animal models. Newly emerging approaches to specifically ablate or rejuvenate senescent cells are now the subject of intense study to explore their utility to provide novel treatments for the aesthetic signs and diseases of aging in humans. Here, we discuss different strategies that are being trialed in vitro, and more recently in vivo, for the targeted removal or reversal of senescent cells. Finally, we describe the evidence for a newly emerging molecular mechanism that may underpin senescence; dysregulation of alternative splicing. We will explore the potential of restoring splicing regulation as a novel "senotherapeutic" approach and discuss strategies by which this could be integrated into the established portfolio of skin aging therapeutics. Cellular senescence is a state of stable cell cycle arrest that has increasingly been linked with cellular, tissue, and organismal aging; targeted removal of senescent cells brings healthspan and lifespan benefits in animal models. Newly emerging approaches to specifically ablate or rejuvenate senescent cells are now the subject of intense study to explore their utility to provide novel treatments for the aesthetic signs and diseases of aging in humans. Here, we discuss different strategies that are being trialed in vitro, and more recently in vivo, for the targeted removal or reversal of senescent cells. Finally, we describe the evidence for a newly emerging molecular mechanism that may underpin senescence; dysregulation of alternative splicing. We will explore the potential of restoring splicing regulation as a novel "senotherapeutic" approach and discuss strategies by which this could be integrated into the established portfolio of skin aging therapeutics.