The relationship between lipofuscin pigment and ageing in the human nervous system

Mann, David; Yates, P. O.; Stamp, J.E.

doi:10.1016/0022-510x(78)90229-0

Cited by 144 publications

(49 citation statements)

References 15 publications

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“…The positive linear correlation between age and the LB area proportion in human and non-human primate beta cells is similar to data derived from LB distribution in post-mitotic cells in other organs such as the human brain [23,29,30] and rat cardiac myocytes and neurons [24,31,32] and extends the observations made previously on 'lipid-storing vesicles' [26]. Lipofuscin is similar in appearance to ceroid, which accumulates rapidly as a result of pathological conditions such as neurodegenerative and genetic diseases but is not age-related [33].…”

Section: Discussionsupporting

confidence: 65%

The long lifespan and low turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation

et al. 2009

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Aims/hypothesis Defects in pancreatic beta cell turnover are implicated in the pathogenesis of type 2 diabetes by genetic markers for diabetes. Decreased beta cell neogenesis could contribute to diabetes. The longevity and turnover of human beta cells is unknown; in rodents <1 year old, a half-life of 30 days is estimated. Intracellular lipofuscin body (LB) accumulation is a hallmark of ageing in neurons. To estimate the lifespan of human beta cells, we measured beta cell LB accumulation in individuals aged 1-81 years. Methods LB content was determined by electron microscopical morphometry in sections of beta cells from human (nondiabetic, n=45; type 2 diabetic, n=10) and non-human primates (n=10; 5-30 years) and from 15 mice aged 10-99 weeks. Total cellular LB content was estimated by threedimensional (3D) mathematical modelling. Results LB area proportion was significantly correlated with age in human and non-human primates. The proportion of human LB-positive beta cells was significantly related to age, with no apparent differences in type 2 diabetes or obesity. LB content was low in human insulinomas (n=5) and alpha cells and in mouse beta cells (LB content in mouse <10% human). Using 3D electron microscopy and 3D mathematical modelling, the LB-positive human beta cells (representing aged cells) increased from ≥90% (<10 years) to ≥97% (>20 years) and remained constant thereafter. Conclusions/interpretation Human beta cells, unlike those of young rodents, are long-lived. LB proportions in type 2 diabetes and obesity suggest that little adaptive change occurs in the adult human beta cell population, which is largely established by age 20 years.

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Section: Discussionsupporting

confidence: 65%

The long lifespan and low turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation

et al. 2009

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“…• An increase in the lipofuscin content of neurons [42]. The amount of lipofuscin that accumulates varies considerably from one type of neuron to another, but it tends to accumulate more in large cortical and thalamic neurons, inferior olive neurons and motor neurons than in others.…”

Section: Microscopic Brain Changes With Agementioning

confidence: 99%

Ageing and the brain

2007

The Journal of Pathology

177

111

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In this review, the evidence for changes in the human brain with ageing at both the macroscopic and microscopic levels is summarized. Loss of neurons is now recognized to be more modest than initial studies suggested and only affects some neuron populations. Accompanying loss of neurons is some reduction in the size of remaining neurons. This reflects a reduced size of dendritic and axonal arborizations. Some of the likely causes of these changes, including free radical damage resulting from a high rate of oxidative metabolism in neurons, glycation and dysregulation of intracellular calcium homeostasis, are discussed. The roles of genes and environmental factors in causing and responding to ageing changes are explored.

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“…Lipofuscin is the ''aging pigment'' that builds up in postmitotic neurons with age (Brizzee, 1981;Terman and Brunk, 2004;Gray and Woulfe, 2005). Many studies have shown that lipofuscin accumulation is especially pronounced in neurons of the IO, and most find that there is a linear accumulation of lipofuscin with increasing age, albeit with a lot of variability (Issidorides and Shanklin, 1961;Barden, 1970;Brizzee et al, 1974;Mann and Yates, 1974;Mann et al, 1978;Drach et al, 1994). One study measured levels of lipofuscin among neurons in the IO of single individuals and found a high degree of cell to cell variability (Drach et al, 1994).…”

Section: Structure Of the Human Ioprmentioning

confidence: 99%

“…We also wondered if the neurochemical differences among species might be related to known species differences in the accumulation of lipofuscin, the ''age pigment,'' in neurons of the IOpr (Dayan, 1971;Mann and Yates, 1974;Mann et al, 1978). Figure 15 shows images of autofluorescence in the IOpr of four human cases, one monkey, and one chimpanzee.…”

Section: Lipofuscin In the Ioprmentioning

confidence: 99%

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Neurochemical and Structural Organization of the Principal Nucleus of the Inferior Olive in the Human

Baizer

Sherwood

Hof

et al. 2011

The Anatomical Record

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The inferior olive (IO) is the sole source of the climbing fibers that innervate the Purkinje cells of the cerebellar cortex. The IO comprises several subdivisions, the dorsal accessory olive (DAO), medial accessory olive (MAO), and principal nuclei of the IO (IOpr); the relative sizes of these subnuclei vary among species. In human, there is an expansion of the cerebellar hemispheres and a corresponding expansion of the IOpr. We have examined the structural and neurochemical organization of the human IOpr, using sections stained with cresyl violet (CV) or immunostained for the calcium-binding proteins calbindin (CB), calretinin (CR), and parvalbumin (PV), the synthetic enzyme for nitric oxide (nNOS), and nonphosphorylated neurofilament protein (NPNFP). We found qualitative differences in the folding patterns of the IOpr among individuals and between the two sides of the brainstem. Quantification of IOpr volumes and indices of folding complexity, however, did not reveal consistent left-right differences in either parameter. Single-label immunohistochemistry showed that populations of neurons in the IOpr express CB, CR, NPNFP, and nNOS. Individual fibers labeled for PV, CB, CR, NPNFP, and nNOS were also found. There was individual variability in the numbers and density of stained neurons in the human IOpr; such variability was not seen in other brainstem nuclei. These data are consistent with, and complement, earlier studies showing a dramatic age-related increase in lipofuscin and decrease in RNA in the human IOpr. The impact of these changes in the IOpr on cerebellar function is, however, not known. Anat Rec, 294:1198Rec, 294: -1216Rec, 294: , 2011. V V C 2011 Wiley-Liss, Inc.

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The relationship between lipofuscin pigment and ageing in the human nervous system

Cited by 144 publications

References 15 publications

The long lifespan and low turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation

The long lifespan and low turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation

Ageing and the brain

Neurochemical and Structural Organization of the Principal Nucleus of the Inferior Olive in the Human

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