Cell structure, function and adaptation
C. Simon Herrington in Muir's Textbook of Pathology, 2020
Further evidence that genetic control of ageing occurs comes from developmental genetic studies in the nematode Caenorhabditis elegans in which mutations of a gene called clk-1 (the ‘clock’ gene) result in elongation of lifespan. Although homologues of these genes in primitive organisms may exist in humans, it is true that wear and tear is a major factor in ageing. Oxidative metabolism generates free radicals and over time these cause progressive damage to cell membranes, DNA, the cytoskeleton, and enzymes. Damaged lipids accumulate in cells in the form of lipofuscin, a giveaway sign of cellular ageing and damage. Although protective mechanisms exist to repair DNA and to remove damaged protein and oxidized lipid, there is gradual attrition over time that eventually leads to the cell's demise.
Urinary System
Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard in Toxicologic Pathology, 2018
Pigment may be commonly noted in the kidneys of not only rats, but also mice, dogs, minipigs, and monkeys as a background finding. This pigment, which can be increased by the administration of some drugs, is most often considered to be lipofuscin, and is most abundant within the proximal tubules (Schneider and Busch 1999). Liposfuscin and some other iron pigments have been reported to accumulate within the renal tubules following administration of certain cephalosporins and several other compounds, but they usually are not associated with degeneration or necrosis. Special stains show increased accumulation in the endolysosomal compartments of proximal tubules, where they appear to be complexed with other proteins, including ALB. Lipofuscin has been associated with increased cellular metabolism and may, therefore, be considered a physiologic response to drug administration rather than necessarily a true toxic response to cell injury. Bilirubin pigments may also be noted in the kidneys in animals with concurrent hepatic insult. Bilirubin accumulation may be related to pharmaceutical inhibition of OATP1B1 transport or inhibition of UGT1A1 conjugation in the liver, resulting in systemic jaundice as well as renal accumulation. Both bilirubin and hemosiderin may accumulate in tubules with drugs that induce overwhelming hemolysis.
The aging body
Jennifer R. Sasser, Harry R. Moody in Gerontology, 2018
Within the cell there are specific smaller structures implicated in aging. For example, mitochondria are the power source within cells. Mitochondria change their shape with aging, which may imply diminished energy with aging. Lipofuscin is a kind of “debris” that accumulates in cells with aging and it may interfere with cell function over the course of aging. But lipofuscin doesn’t accumulate in all cells of the body. The accumulation of lipofuscin is a distinctive hallmark of aging and accumulation of this “debris” occurs at a rate inversely related to longevity. It turns out that accumulation of lipofuscin is linked to macular degeneration, a degenerative disease of the eye that is age-related, though not caused by normal aging itself.
Secretory autophagy: a turn key for understanding AMD pathology and developing new therapeutic targets?
Published in Expert Opinion on Therapeutic Targets, 2022
Janusz Blasiak, Kai Kaarniranta
Due to its chemical nature, lipofuscin cannot be degraded and is accumulated within the lysosomes and cytosols of long-lived, post-mitotic, senescent, or quiescent cells. Therefore, post-mitotic photoreceptors and quiescent RPE cells are predisposed to accumulate lipofuscin. Moreover, as cellular senescence is a main player in AMD pathogenesis, its effect may be potentiated by lipofuscin accumulation and vice versa. Resistance of lipofuscin to proteostasis and its accumulation affects the proteasome, lysosome, degradative and chaperone-mediated autophagy [47,50]. Accumulation of lipofuscin may fuel a vicious cycle, as its cytosolic and lysosomal deposits may produce RONS oxidizing proteins, lipids and carbohydrates leading to further production of lipofuscin. Cells overloaded with lipofuscin may die from apoptosis due to inhibited proteostasis of proapoptotic proteins and blockage of the nuclear factor-kappa-B (NFKB) protein complex cellular signaling [50].
The Effect of Resveratrol on Radioiodine Therapy-Associated Lacrimal Gland Damage
Published in Current Eye Research, 2021
Gökhan Koca, Evin Singar, Aylin Akbulut, Nuray Yazihan, Nihat Yumuşak, Ayten Demir, Meliha Korkmaz
The differences between the cells were determined semi-quantitatively under 200 magnification by choosing 10 random microscopic areas. Fibrosis was graded as 0 when it is absent; as 1 when it is focal and within 1 lobule; as 2 when it is less than 50% of the lobules; as 3 when it is diffuse in more than 50% of the lobules. The evaluation of inflammatory cells was determined by taking into consideration the inflammation density in each microscope field. In the evaluation of hyperemia, vessels dilated and lumen filled with erythrocytes were considered as hyperemia. Lipofuscin-like accumulation was defined as the number of cells with age-related pigments accumulated per lobule. The presence of lipofuscin was graded as 0 when absent, grade 1 as very few, grade 2 as less than 50%, and grade 3 as more than 50% of the gland. In nucleus changes and vacuolization, the numeric values were graded as 0 when it is between 0 and 3; as 1 when it is less than or equal to 20 cells with cellular changes; as 2 when it is between 21 and 50 cells with cellular changes; as 3 when it is more than 50 with cellular changes.
Complement inhibition as a therapeutic strategy in retinal disorders
Published in Expert Opinion on Biological Therapy, 2019
Enoch Kassa, Thomas A. Ciulla, Rehan M. Hussain, Pravin U. Dugel
Autosomal recessive Stargardt macular dystrophy (STGD1) is a dystrophy resulting from mutations in the ABCA4 (ABCR) gene. It is the most common form of inherited juvenile macular degeneration, affecting roughly in 1 in 10,000 people. Mutations in ABCA4 also result in RP and cone-rod dystrophy. The age of onset of juvenile and early adult STGD1 is usually 8–25 years with some cases occurring in older adults (late-adult onset STGD1) [45,46]. A hallmark of the disease is premature accumulation of lipofuscin (a brown-yellow autofluorescent pigment associated with aging) in the RPE of the eye, causing a pattern of yellowish flecks that extend outward from the macula. Lipofuscin is also found in cells of the liver, kidney, heart muscle, adrenals, nerve, and ganglion and is considered one of the most consistent morphologic features of aging, with a rate of accumulation inversely related to longevity [47,48]. However, it is thought that the mechanisms involved in RPE lipofuscin formation are closely related to metabolic pathways that are specific to the retina and fundamentally different from mechanisms found in other tissues [49].”