Reductions in Gray Matter Linked to Epigenetic HIV-Associated Accelerated Aging.

A growing literature suggests a relationship between HIV-infection and a molecular profile of age acceleration. However, despite the widely known high prevalence of HIV-related brain atrophy and HIV-associated neurocognitive disorder (HAND), epigenetic age acceleration has not been linked to HIV-related changes in structural MRI. We applied morphological MRI methods to study the brain structure of 110 virally suppressed participants with HIV infection and 122 uninfected controls age 22-72. All participants were assessed for cognitive impairment, and blood samples were collected from a subset of 86 participants with HIV and 83 controls to estimate epigenetic age. We examined the group-level interactive effects of HIV and chronological age and then used individual estimations of epigenetic age to understand the relationship between age acceleration and brain structure. Finally, we studied the effects of HAND. HIV-infection was related to gray matter reductions, independent of age. However, using epigenetic age as a biomarker for age acceleration, individual HIV-related age acceleration was associated with reductions in total gray matter. HAND was associated with decreases in thalamic and hippocampal gray matter. In conclusion, despite viral suppression, accentuated gray matter loss is evident with HIV-infection, and greater biological age acceleration specifically relates to such gray matter loss.

Premature Physiologic Aging as a Paradigm for Understanding Increased Risk of Adverse Health Across the Lifespan of Survivors of Childhood Cancer.

The improvement in survival of childhood cancer observed across the past 50 years has resulted in a growing acknowledgment that simply extending the lifespan of survivors is not enough. It is incumbent on both the cancer research and the clinical care communities to also improve the health span of survivors. It is well established that aging adult survivors of childhood cancer are at increased risk of chronic health conditions, relative to the general population. However, as the first generation of survivors age into their 50s and 60s, it has become increasingly evident that this population is also at risk of early onset of physiologic aging. Geriatric measures have uncovered evidence of reduced strength and speed and increased fatigue, all components of frailty, among survivors with a median age of 33 years, which is similar to adults older than 65 years of age in the general population. Furthermore, frailty in survivors independently increased the risk of morbidity and mortality. Although there has been a paucity of research investigating the underlying biologic mechanisms for advanced physiologic age in survivors, results from geriatric populations suggest five biologically plausible mechanisms that may be potentiated by exposure to cancer therapies: increased cellular senescence, reduced telomere length, epigenetic modifications, somatic mutations, and mitochondrial DNA infidelity. There is now a critical need for research to elucidate the biologic mechanisms of premature aging in survivors of childhood cancer. This research could pave the way for new frontiers in the prevention of these life-changing outcomes.

[Modern approaches to correction and prophylaxis of premature aging using adaptogenes of plant origin].

Last years, the big attention is given studying of the methods promoting increase of the immune status of an organism, got under influence of extreme factors, in particular, ionas radiations. In this connection perspectivity of application of laboratory diagnostics for testing a degree of defeat of immune system and application phytoadaptogenes is proved, namely: tinctures of a Panacis ginseng, Schizandrae chinensis, an extract Elaetherococcus for correction of such conditions.

[Radiation-protective action of bioantioxidant complex of ginseng extract in the model of the radiation-induced aging during development of radiation-induced neoplasms].

The study of the geriatric properties of the bioantioxidant complex "Neovitin" received from a biomass of ginseng, against formation of radio gene tumors was continued. The preparation was applied to the laboratory animals exposed to chronic gamma irradiation by low doses, by all period of irradiation and thirty days in the post beam period. The expressed anticancerogenic effect of "Neovitin", reducing formation of radio gene tumors, including malignant, as well as reduction of a spectrum of new growths were proved.

Immune dysregulation and chronic stress among older adults: a review.

Aging is associated with a natural dysregulation in immune functioning which may be amplified when it occurs in the context of chronic stress. Family dementia caregiving provides an excellent model to study the impact of chronic stress on immune functioning among older individuals. Empirical data suggest that the stress of caregiving dysregulates multiple components of innate and adaptive immunity. Elderly caregivers have poorer responses to vaccines, impaired control of latent viruses, exaggerated production of inflammatory mediators and accelerated cellular aging, compared to noncaregiving older adults. The chronic stress-induced immune dysregulation observed among older caregivers appears to be of sufficient magnitude to impact health. Furthermore, evidence suggests that chronic stress leads to premature aging of the immune system.

Tobacco smoke causes premature skin aging.

Smoking tobacco is the most preventable cause of morbidity and is responsible for more than three million deaths a year worldwide. In addition to a strong association with a number of systemic diseases, smoking is also associated with many dermatological conditions, including poor wound healing, premature skin aging, squamous cell carcinoma, melanoma, oral cancer, acne, psoriasis, and hair loss. This review focuses on the effects of smoking on premature skin aging. It has been long established that smoking has deleterious effects on skin. Epidemiological studies indicate that smoking is an important environmental factor in premature skin aging. In vitro studies indicate that tobacco smoke extract impairs the production of collagen and increases the production of tropoelastin and matrix metalloproteinases (MMP), which degrade matrix proteins, and also causes an abnormal production of elastosis material. Smoking increases MMP levels, which leads to the degradation of collagen, elastic fibers, and proteoglycans, suggesting an imbalance between biosynthesis and degradation in dermal connective tissue metabolism. Reactive oxygen species are also involved in tobacco smoke-induced premature skin aging. Scavengers of reactive oxygen species ameliorate the induction of MMP. Tobacco smoke extract also impacts dermal connective tissue in nude mice. Thus, in vitro and in vivo evidence indicates that smoking tobacco leads to accelerated aging of the skin. These findings might be useful to motivate those patients who are more concerned about their appearance than the potential internal damage associated with smoking to stop smoking.

From old organisms to new molecules: integrative biology and therapeutic targets in accelerated human ageing.

Understanding the basic biology of human ageing is a key milestone in attempting to ameliorate the deleterious consequences of old age. This is an urgent research priority given the global demographic shift towards an ageing population. Although some molecular pathways that have been proposed to contribute to ageing have been discovered using classical biochemistry and genetics, the complex, polygenic and stochastic nature of ageing is such that the process as a whole is not immediately amenable to biochemical analysis. Thus, attempts have been made to elucidate the causes of monogenic progeroid disorders that recapitulate some, if not all, features of normal ageing in the hope that this may contribute to our understanding of normal human ageing. Two canonical progeroid disorders are Werner's syndrome and Hutchinson-Gilford progeroid syndrome (also known as progeria). Because such disorders are essentially phenocopies of ageing, rather than ageing itself, advances made in understanding their pathogenesis must always be contextualised within theories proposed to help explain how the normal process operates. One such possible ageing mechanism is described by the cell senescence hypothesis of ageing. Here, we discuss this hypothesis and demonstrate that it provides a plausible explanation for many of the ageing phenotypes seen in Werner's syndrome and Hutchinson-Gilford progeriod syndrome. The recent exciting advances made in potential therapies for these two syndromes are also reviewed.