A hypothesis for cell aging in mature adipocytes
Chronological changes in metabolism and functions of cultured adipocytes: a hypothesis for cell aging in mature adipocytes
Yi-Hao Yu and Huaijie Zhu
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032
Submitted 3 June 2003; accepted in final form 13 November 2003
SUMMARY
Yu and Zhu investigated chronological changes in metabolism and function of adipocytes in vitro. In a tissue culture system, they grew 3T3-L1 preadipocytes, which were then induced to differentiate as adipocytes. They characterized several factors as variables of cell age. They observed that as adipocytes aged, there was a corresponding elevation in the expression of aging markers Bax and lipopolysaccharide-induced TNF-_ Factor (LITAF). These two proteins play a role in the proapoptotic scene. The researchers also observed a decrease in fuel uptake and overall cellular catabolism as cells aged. Glucose uptake decreased, as did the CO2 production rate (measure of cellular respiration rate) during adipocyte aging (CO2 production initially increases and stabilizes after differentiation; the decrease is observed in relation to this stabilized value at maturation). Catabolic activities were also characterized; as cells aged there was a decrease in insulin sensitivity, as well reduced gene expression of secretory proteins adiponectin and leptin. While these observations of cell aging were a cell culture phenomenon, this data suggest that similar characteristics of adipocyte aging, namely being more metabolically inert, may be found in vivo.
WHY I CHOSE THIS PAPER
By characterizing the observed metabolic changes that occur during adipocyte aging, this paper provides a baseline with which to measure cell aging in a specific cell line in vitro. I am interested the SENS platform for reversing cell aging, particularly the role of "extracellular junk." This baseline allows us a method to measure cell age in our experiments. While characteristics of an observed cell aging process cannot necessarily and simply be turned into indicators of cell vaibility and youthfulness, it is perhaps a start in my search for a way to gauge the slow or reversal of cell aging in an in vitroexperiment for this class
5 comments:
This seems like a really interesting research topic! How did the researchers induce the preadipocytes to differentiate into adipocytes? Also, what is the importance of insulin sensitivity for these cells and how did the researchers quantitatively assess this information? Can you also explain more what you mean by the “SENS platform” and the role of “extracellular junk”?
I think the possible reversal of cell aging is a very cool subject to study. Is there a reason why they have specifically cared to know the factors involved in aging of adipocytes, or did they just want to find the factors influencing the cell aging and just randomly picked adipocytes?
Besides that your paper review is so perfectly worded that I really enjoyed reading it.
This paper is interesting. what were the exact methods used for measuring the indicators of cell aging?
Arezu:Here is the differentiation process:
"3T3-L1 cells were plated at a density of 1x10^ 5 cells/35-mm dish (6-well plates). Forty-eight hours after reaching confluence, cells were incubated in an
induction medium of high-glucose DMEM containing 10% fetal
bovine serum, 1 microM dexamethasone, 500 microM IBMX, and 5 microg/ml insulin. At postinduction day (PID) 3, the medium was changed to a
growth medium containing high-glucose DMEM and 10% fetal bovine serum. The culture medium was routinely changed every other
day."
To assess insulin sensitivity, the group measured the uptake of 2-deoxyglucose, in the absence of cold glucose in the medium, of cells at various ages. A low sensitivity would be correlated with increasing insulin resistance, which is important metabolically.
SENS stands for "Strategies for Engineered Negligible Senescence." Visit sens.org for the platform. They also have an excellent, concise explanation for the role of extracellular junk.
Azadeh: It appears that the group was specifically interested in the aging of adipocytes, since they mention their interest in investigating in the role of adipose cell aging in tissue function. However, the alternative you pose is also possible; perhaps they looked for the physiological significance after noticing something interesting in adipocytes. I'm glad you enjoyed reading!
Brian: Quantitative RT-PCR, CO2 measurement assay that traps labeled CO2 over a defined time period, ATP measurement assay involving a luciferase-luciferin reagent, trypan blue staining, DNA content quantification (for cell # determination), triglyceride turnover assay, [3H]glycerol incorporation assay, free glycerol release assay, etc. See paper for details.
‘Aging’, or becoming unhealthy with time, is a compound problem triggered by the combined effect of a variety of factors. The SENS platform suggests that these factors are part of the natural cellular metabolic functions and are too complicated to tamper with. It can be contested that measuring the activity of any particular metabolic function is insufficient for accurately measuring ‘aging’, since the interaction and combined effect of all factors are important. In other words, it is misleading to only consider a select number of indications of aging, because even if those select factors are ‘healed’ with a particular therapy, there is no guarantee that ‘aging’ is reduced. This is so because the particular therapy, although alleviating some symptoms of aging, may stress other cellular mechanisms and subsequently cause more damage. Also, even if the therapy is successful at correcting a particular aging symptom, other symptoms that are overlooked will persist and can cause ‘aging’ nevertheless. Therefore, since the cellular metabolism is too complicated to allow for the consideration of every metabolic factor, I would suggest that a more general and systems based approach is necessary, as described in the SENS platform. Nevertheless, the factors described in this paper are useful for measuring the overall health and ‘age’ of the cell, and may be handy for preliminary explorations of SENS.
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