The Aging Adipose Organ: Lipid Redistribution, Inflammation, and Cellular Senescence

Aging is a time-related process of functional decline at organelle, cellular, tissue, and organismal level that ultimately limits life. Cellular senescence is a state of permanent growth arrest in response to stress and one of the major drivers of aging and age-related disorders. Senescent cells accumulate with age, and removal of these cells delays age-related disorders in different tissues and prolongs healthy lifespan. One of the most studied aging mechanisms is the accumulation of reactive oxygen species damage in cells, organs, and organisms over time. Elevated oxidative stress is also found in metabolic diseases such as obesity, metabolic syndrome and associated disorders. Moreover, dysregulation of the energy homeostasis is also associated with aging, and many age-related genes also control energy metabolism, with the adipose organ, comprising white, brite, and brown adipocytes, as an important metabolic player in the regulation of whole-body energy homeostasis. This review summarizes transformations in the adipose organ upon aging and cellular senescence and sheds light on the reallocation of fat mass between adipose depots, on the metabolism of white and brown adipose tissue, on the regenerative potential and adipogenic differentiation capacity of preadipocytes, and on alterations in mitochondria and bioenergetics. In conclusion, the aging process is a lifelong, creeping process with gradual decline in (pre-)adipocyte function over time. Thus, slowing down the accumulation of (pre-)adipocyte damage and dysfunction, removal of senescent preadipocytes as well as blocking deleterious compounds of the senescent secretome are protective measures to maintain a lasting state of health at old age.

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Lamin B receptor: role on chromatin structure, cellular senescence and possibly aging

Biochemical Journal ◽

10.1042/bcj20200165 ◽

2020 ◽

Vol 477 (14) ◽

pp. 2715-2720

Author(s):

Susana Castro-Obregón

Keyword(s):

Cellular Senescence ◽

Nuclear Membrane ◽

Chromatin Structure ◽

Cholesterol Synthesis ◽

Reductase Activity ◽

Chimeric Protein ◽

Nuclear Lamina ◽

Lamin B ◽

Inner Nuclear Membrane ◽

Lamin B Receptor

The nuclear envelope is composed by an outer nuclear membrane and an inner nuclear membrane, which is underlain by the nuclear lamina that provides the nucleus with mechanical strength for maintaining structure and regulates chromatin organization for modulating gene expression and silencing. A layer of heterochromatin is beneath the nuclear lamina, attached by inner nuclear membrane integral proteins such as Lamin B receptor (LBR). LBR is a chimeric protein, having also a sterol reductase activity with which it contributes to cholesterol synthesis. Lukasova et al. showed that when DNA is damaged by ɣ-radiation in cancer cells, LBR is lost causing chromatin structure changes and promoting cellular senescence. Cellular senescence is characterized by terminal cell cycle arrest and the expression and secretion of various growth factors, cytokines, metalloproteinases, etc., collectively known as senescence-associated secretory phenotype (SASP) that cause chronic inflammation and tumor progression when they persist in the tissue. Therefore, it is fundamental to understand the molecular basis for senescence establishment, maintenance and the regulation of SASP. The work of Lukasova et al. contributed to our understanding of cellular senescence establishment and provided the basis that lead to the further discovery that chromatin changes caused by LBR reduction induce an up-regulated expression of SASP factors. LBR dysfunction has relevance in several diseases and possibly in physiological aging. The potential bifunctional role of LBR on cellular senescence establishment, namely its role in chromatin structure together with its enzymatic activity contributing to cholesterol synthesis, provide a new target to develop potential anti-aging therapies.

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Ginger (Zingiber officinale) Extract Promotes Telomere Shortening and Induces Cellular Senescence in A549 Lung Cancer Cells

10.1055/s-0037-1608062 ◽

2017 ◽

Author(s):

N Kaewtunjai ◽

W Pompimon ◽

W Tuntiwechapikul

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Cellular Senescence ◽

Zingiber Officinale ◽

Lung Cancer Cells ◽

Telomere Shortening ◽

A549 Lung

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STUDIES IN CONGENITAL GENERALIZED LIPODYSTROPHY (SEIP-BERARDINELLI SYNDROME)

Acta Endocrinologica ◽

10.1530/acta.0.0720475 ◽

1973 ◽

Vol 72 (3) ◽

pp. 475-494 ◽

Cited By ~ 21

Author(s):

Svein Oseid

Keyword(s):

Insulin Resistance ◽

Glucose Tolerance ◽

Normal Glucose Tolerance ◽

Juvenile Form ◽

Congenital Generalized Lipodystrophy ◽

Glucose Levels ◽

Normal Glucose ◽

Glucose Tolerance Tests ◽

The One ◽

Adipose Organ

ABSTRACT Six cases of congenital generalized lipodystrophy have been studied at different ages from infancy to adolescence with regard to glucose tolerance, insulin secretion, and insulin sensitivity. During the first few years of life there is normal glucose tolerance. The fasting immuno-reactive insulin (IRI) levels are either slightly elevated or normal. The IRI response to glucose is exaggerated and prolonged, at least from the third year of life. Some degree of insulin resistance is already present in infancy. From the age of 8–10 years glucose tolerance decreases rapidly. The fasting IRI levels are usually grossly elevated, while fasting plasma glucose levels are only moderately elevated or normal. The IRI responses to oral and iv administered glucose, and to tolbutamide are exaggerated; the insulinogenic indices are high. Cortisone primed glucose tolerance tests become abnormal. Insulin resistance is marked, and increases with age. After cessation of growth at approximately 12 years of age, frank diabetes with fasting hyperglycaemia and diabetic glucose tolerance curves developed in the one patient followed beyond this age. Her fasting IRI was increased, but there was a poor IRI response to glucose stimulation, suggesting a partial exhaustion of the β-cells. Her initial IRI response to tolbutamide was still good, but not as brisk as in the younger patients. This type of diabetes is quite different from the juvenile form, and also from the diabetes of older age. It may be causally related to the lack of an adequate adipose organ necessary for the disposal of excesses of glucose, or possibly related to another anti-insulin mechanism.

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