706 research outputs found
Curcumin in Cell Death Processes: A Challenge for CAM of Age-Related Pathologies
Curcumin, the yellow pigment from the rhizoma of Curcuma longa, is a widely studied phytochemical which has a variety of biological activities: anti-inflammatory and anti-oxidative. In this review we discuss the biological mechanisms and possible clinical effects of curcumin treatment on cancer therapy, and neurodegenerative diseases such as Alzheimer's Disease, with particular attention to the cell death processes induced by curcumin. Since oxidative stress and inflammation are major determinants of the aging process, we also argue that curcumin can have a more general effect that slows down the rate of aging. Finally, the effects of curcumin can be described as xenohormetic, since it activates a sort of stress response in mammalian cells
The Dual Role of the Pervasive "Fattish" Tissue Remodeling With Age
Human aging is characterized by dramatic changes in body mass composition that include a general increase of the total fat mass. Within the fat mass, a change in the proportions of adipose tissues also occurs with aging, affecting body metabolism, and playing a central role in many chronic diseases, including insulin resistance, obesity, cardiovascular diseases, and type II diabetes. In mammals, fat accumulates as white (WAT) and brown (BAT) adipose tissue, which differ both in morphology and function. While WAT is involved in lipid storage and immuno-endocrine responses, BAT is aimed at generating heat. With advancing age BAT declines, while WAT increases reaching the maximum peak by early old age and changes its distribution toward a higher proportion of visceral WAT. However, lipids tend to accumulate also within lipid droplets (LDs) in non-adipose tissues, including muscle, liver, and heart. The excess of such ectopic lipid deposition and the alteration of LD homeostasis contribute to the pathogenesis of the above-mentioned age-related diseases. It is not clear why age-associated tissue remodeling seems to lean toward lipid deposition as a "default program." However, it can be noted that such remodeling is not inevitably detrimental. In fact, such a programmed redistribution of fat throughout life could be considered physiological and even protective, in particular at extreme old age. In this regard, it has to be considered that an excessive decrease of subcutaneous peripheral fat is associated with a pro-inflammatory status, and a decrease of LD is associated with lipotoxicity leading to an increased risk of insulin resistance, type II diabetes and cardiovascular diseases. At variance, a balanced rate of fat content and distribution has beneficial effects for health and metabolic homeostasis, positively affecting longevity. In this review, we will summarize the present knowledge on the mechanisms of the age-related changes in lipid distribution and we will discuss how fat mass negatively or positively impacts on human health and longevity
Accelerated bio-cognitive aging in Down syndrome: State of the art and possible deceleration strategies
Down syndrome (DS) has been proposed by George Martin as a segmental progeroid
syndrome since 1978. In fact, DS persons suffer from several age-associated
disorders much earlier than euploid persons. Furthermore, a series of recent
studies have found that DS persons display elevated levels of age biomarkers,
thus supporting the notion that DS is a progeroid trait. Nowadays, due to the
progressive advancements in social inclusion processes and medical assistance, DS
persons live much longer than in the past; therefore, the early-onset health
problems of these persons are becoming an urgent and largely unmet social and
medical burden. In particular, the most important ailment of DS persons is the
accelerated cognitive decline that starts when they reach about 40 years of age.
This decline can be at least in part counteracted by multi-systemic approaches
including early-onset cognitive training, physical activity, and psychosocial
assistance. However, no pharmacological treatment is approved to counteract this
decline. According to the most advanced conceptualization of Geroscience,
tackling the molecular mechanisms underpinning the aging process should be a
smart/feasible strategy to combat and/or delay the great majority of age-related
diseases, including cognitive decline. We think that a debate is needed urgently
on if (and how) this strategy could be integrated in protocols to face
DS-associated dementia and overall unhealthy aging. In particular we propose
that, on the basis of data obtained in different clinical settings, metformin is
a promising candidate that could be exploited to counteract cognitive decline in
DS
X-chromosome-linked miR548am-5p is a key regulator of sex disparity in the susceptibility to mitochondria-mediated apoptosis.
Sex dimorphism in cell response to stress has previously been investigated by different research groups. This dimorphism could be at least in part accounted for by sex-biased expression of regulatory elements such as microRNAs (miRs). In order to spot previously unknown miR expression differences we took advantage of prior knowledge on specialized databases to identify X chromosome-encoded miRs potentially escaping X chromosome inactivation (XCI). MiR-548am-5p emerged as potentially XCI escaper and was experimentally verified to be significantly up-regulated in human XX primary dermal fibroblasts (DFs) compared to XY ones. Accordingly, miR-548am-5p target mRNAs, e.g. the transcript for Bax, was differently modulated in XX and XY DFs. Functional analyses indicated that XY DFs were more prone to mitochondria-mediated apoptosis than XX ones. Experimentally induced overexpression of miR548am-5p in XY cells by lentivirus vector transduction decreased apoptosis susceptibility, whereas its down-regulation in XX cells enhanced apoptosis susceptibility. These data indicate that this approach could be used to identify previously unreported sex-biased differences in miR expression and that a miR identified with this approach, miR548am-5p, can account for sex-dependent differences observed in the susceptibility to mitochondrial apoptosis of human DFs
Demography of the bottlenose dolphin Tursiops truncatus (Mammalia: Delphinidae) in the Eastern Ligurian Sea (NW Mediterranean): quantification of female reproductive parameters
AbstractThe reproductive histories of 41 adult bottlenose dolphin females were analysed using photo-identification data collected between 2006 and 2014 in four sub-areas of the eastern Ligurian Sea (northwest Mediterranean). The Rapallo sub-area revealed the highest (highly significant) frequency of encounters (per unit effort) of reproductive females in association with young individuals, therefore emerging as a candidate nursery area in the region. The estimated fertility rate of adult females ranged between 290 and 407 births per 1000 individuals per year, higher than that of other known bottlenose dolphin populations, with a calving interval between 2.45 and 3.5 years. These results will be useful for projecting future trends of this (sub)population
Muscle-specific Perilipin2 down-regulation affects lipid metabolism and induces myofiber hypertrophy.
BACKGROUND: Perilipin2 (Plin2) belongs to a family of five highly conserved
proteins, known for their role in lipid storage. Recent data indicate that Plin2
has an important function in cell metabolism and is involved in several human
pathologies, including liver steatosis and Type II diabetes. An association
between Plin2 and lower muscle mass and strength has been found in elderly and
inactive people, but its function in skeletal muscle is still unclear. Here, we
addressed the role of Plin2 in adult muscle by gain and loss of function
experiments.
METHODS: By mean of in vivo Plin2 down-regulation (shPlin2) and overexpression
(overPlin2) in murine tibialis anterior muscle, we analysed the effects of Plin2
genetic manipulations on myofiber size and lipid composition. An analysis of
skeletal muscle lipid composition was also performed in vastus lateralis samples
from young and old patients undergoing hip surgery.
RESULTS: We found that Plin2 down-regulation was sufficient to induce a 30%
increase of myofiber cross-sectional area, independently of mTOR pathway.
Alterations of lipid content and modulation of genes involved in lipid synthesis
occurred in hypertrophic muscles. In particular, we showed a decrease of
triglycerides, ceramides, and phosphatidylcoline:phosphatidylethanolamine ratio,
a condition known to impact negatively on muscle function. Plin2 overexpression
did not change fibre size; however, lipid composition was strongly affected in a
way that is similar to that observed in human samples from old patients.
CONCLUSIONS: Altogether these data indicate that Plin2 is a critical mediator for
the control of muscle mass, likely, but maybe not exclusively, through its
critical role in the regulation of intracellular lipid content and composition
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