Lifespan, body size and oxygen : aerobic metabolism and oxidative stress in cultured fibroblasts /

The allometric scaling relationship observed between metabolic rate (MR) and species body mass can be partially explained by differences in cellular MR (Porter & Brand, 1995). Here, I studied cultured cell lines derived from ten mammalian species to determine whether cells propagated in an identical environment exhibited MR scaling. Oxidative and anaerobic metabolic parameters did not scale significantly with donor body mass in cultured cells, indicating the absence of an intrinsic MR setpoint. The rate of oxygen delivery has been proposed to limit cellular metabolic rates in larger organisms (West et al., 2002). As such cells were cultured under a variety of physiologically relevant oxygen tensions to investigate the effect of oxygen on cellular metabolic rates. Exposure to higher medium oxygen tensions resulted in increased metabolic rates in all cells. Higher MRs have the potential to produce more reactive oxygen species (ROS) which could cause genomic instability and thus reduced lifespan. Longer-lived species are more resistant to oxidative stress (Kapahi et al, 1999), which may be due to greater antioxidant and/or DNA repair capacities. This hypothesis was addressed by culturing primary dermal fibroblasts from eight mammalian species ranging in maximum lifespan from 5 to 120 years. Only the antioxidant manganese superoxide dismutases (MnSOD) positively scaled with species lifespan (p<0.01). Oxidative damage to DNA is primarily repaired by the base excision repair (BER) pathway. BER enzyme activities showed either no correlation or as in the case of polymerase p correlated, negatively with donor species (p<0.01 ). Typically, mammalian cells are cultured in a 20% O2 (atmospheric) environment, which is several-fold higher than cells experience in vivo. Therefore, the secondary aim of this study was to determine the effect of culturing mammalian cells at a more physiological oxygen tension (3%) on BER, and antioxidant, enzyme activities. Consistently, standard culture conditions induce higher antioxidant and DNA ba.se excision repair activities than are present under a more physiological oxygen concentration. Therefore, standard culture conditions are inappropriate for studies of oxidative stress-induced activities and species differences in fibroblast DNA BER repair capacities may represent differences in ability to respond to oxidative stress. An interesting outcome firom this study was that some inherent cellular properties are maintained in culture (i.e. stress responses) while others are not (i.e. MR).

List of Employees to be involved in the extension of the Port Dalhousie and Thorold Railway

List of Employees to be involved in the extension of the Port Dalhousie and Thorold Railway (1 page, handwritten). This is signed by S.D. Woodruff, Nov. 25, 1856.

Letter of estimate sent to S.D. Woodruff for the total cost of construction and equipment of the extension of the line to Port Colborne

Letter of estimate sent to S.D. Woodruff for the total cost of construction and equipment of the extension of the line to Port Colborne [this is unsigned]. There is an envelope with this letter that suggests that it is from Mr. Shanly, Mar. 12, 1857.

Chart of estimate of cost of Port Dalhousie and Thorold Railway extension Line no. 1

Chart of estimate of cost of Port Dalhousie and Thorold Railway extension Line no. 1 signed by Mr. Shanly, Mar. 12, 1857.

Report sent to the President and Director of the Port Dalhousie and Thorold Railway stating that the location of the line extension of the railway is completed

Report sent to the President and Director of the Port Dalhousie and Thorold Railway stating that the location of the line extension of the railway is completed. The distance from Thorold Station to Port Colborne is 20 miles. The estimate provides for construction of a permanent structure across the Chippewa and Welland River. Estimates for building a first class road, culverts and bridges will be of permanent and durable masonry. This includes estimates for various station buildings such as a warehouse in Port Colborne and a warehouse in Port Dalhousie. Surveys and plans are ready and will be registered this week. This is signed by S.D. Woodruff (2 copies) [one appears to be a rough copy] (The rough copy is 5 pages, handwritten and the other copy is 6 pages, handwritten), Apr. 8, 1857.

Voucher #2 from the Engineer Department of Port Dalhousie and Thorold Railway Extension paid to Daniel Plumsteel, Dec. 31, 1856

Voucher #2 from the Engineer Department of Port Dalhousie and Thorold Railway Extension for surveys, paid to Daniel Plumsteel, Dec. 31, 1856.

Voucher #3 from the Engineer Department of Port Dalhousie and Thorold Railway Extension paid to Thomas Woods, Dec. 31, 1856

Voucher #3 from the Engineer Department of Port Dalhousie and Thorold Railway Extension for sinking test pits, paid to Thomas Woods, Dec. 31, 1856.

Voucher #5 from the Engineer Department of Port Dalhousie and Thorold Railway Extension to George Forbes for surveys, Jan. 31, 1857

Voucher #5 from the Engineer Department of Port Dalhousie and Thorold Railway Extension to George Forbes for surveys, Jan. 31, 1857.

Voucher #6 from the Engineer Department of Port Dalhousie and Thorold Railway Extension to Thomas Woods for surveys, Jan. 31, 1857

Voucher #6 from the Engineer Department of Port Dalhousie and Thorold Railway Extension to Thomas Woods for surveys, Jan. 31, 1857.

Voucher #7 from the Engineer Department of Port Dalhousie and Thorold Railway Extension to W.G. Thompson accompanied by an abstract of vouchers and summaries of account paid by W.G. Thompson for surveys, Jan. 31, 1857

Voucher #7 from the Engineer Department of Port Dalhousie and Thorold Railway Extension to W.G. Thompson accompanied by an abstract of vouchers and summaries of account paid by W.G. Thompson for surveys, Jan. 31, 1857.

Pay roll voucher #8 from the Engineer Department of Port Dalhousie and Thorold Railway Extension for surveys in the month of February, Feb. 28, 1857

Pay roll voucher #8 from the Engineer Department of Port Dalhousie and Thorold Railway Extension for surveys in the month of February, Feb. 28, 1857.

Voucher #9 from the Engineer Department of Port Dalhousie and Thorold Railway Extension to W. G. Thompson accompanied by an abstract of vouchers for surveys, Feb. 28, 1857

Voucher #9 from the Engineer Department of Port Dalhousie and Thorold Railway Extension to W. G. Thompson accompanied by an abstract of vouchers for surveys, Feb. 28, 1857

Pay roll voucher #10 from the Engineer Department of Port Dalhousie and Thorold Railway Extension for the engineer corps. , Mar. 31, 1857

Pay roll voucher #10 from the Engineer Department of Port Dalhousie and Thorold Railway Extension for the engineer corps. , Mar. 31, 1857.

Voucher #15 from the Engineer Department of Port Dalhousie and Thorold Railway Extension to A. H. Armour for office supplies, Apr. 1, 1857

Voucher #15 from the Engineer Department of Port Dalhousie and Thorold Railway Extension to A. H. Armour for office supplies, Apr. 1, 1857.

Pay roll voucher #12 from the Engineer Department of Port Dalhousie and Thorold Railway Extension for the office approved by F. Shanly, chief engineer, April, 1857

Pay roll voucher #12 from the Engineer Department of Port Dalhousie and Thorold Railway Extension for the office approved by F. Shanly, chief engineer, April, 1857.