MOST SIGNIFICANT CONTRIBUTIONS
1. Nutritional Amelioration of Aging Processes: Papers 1-5, 10, 11
Lemon, J.A., Boreham, D.R., Rollo, C.D. 2003. A dietary supplement abolishes age-related cognitive decline in transgenic mice expressing elevated free radical processes. Exp. Biol. Med. 228:800-810. We showed that complex dietary supplements strongly ameliorate aging processes despite failures of simpler formulations. This won the “Best paper of 2003 award” and was the subject of an editorial by a president of the American Aging Society (H. Brown-Borg). Subsequent publications extended results to life extension, radiation resistance, and protection against reactive oxygen and nitrogen species, DNA damage and apoptosis.[1,3,5] We further showed that the supplement maintained larger brains, cognition, motor performance and mitochondrial function in old mice. [1,5] The supplement received international attention (Eleven Television Interviews including The National and The Nature of Things). Rollo was nominated for McMaster University’s 2012 “Innovator of the Year Award.” The supplement provides a powerful experimental tool for our aging studies. We also developed the cricket as a new aging model more suitable than Drosophila for rapidly testing diets on aging and life history features. We have already doubled cricket longevity via several forms of dietary restriction and screened >40 nutraceuticals.[2,4]
2. Aging and the Regulation of Growth and Stress Resistance: Papers 1-6, 8, 10-18
Rollo, C.D., Carlson, J., Sawada, M. 1996. Accelerated aging of giant transgenic mice is associated with elevated free radical processes. Can. J. Zool. 74: 606-620. (76 citations) The allocation paradigm developed in my book (Rollo 1994 see below) proposed that survivorship can be treated as an investment. Consequently, we hypothesized a priori, that the early senescence of transgenic growth hormone mice was due to compromised defence, repair or replacement functions (i.e., stress resistance) via excessive diversion of investments to growth. Reduced antioxidants would increase free radical damage. Confirmation of a strong correlation between free radicals and accelerated aging in these mice supported both the free radical theory of aging and my allocation hypothesis. Energy supplements and our nutraceutical formulation also extended longevity as predicted. The trade-off between growth and stress resistance has now been traced to a “hard-wired” switch in a pathway called PI3K. This switch shunts activity either to growth and production processes or to stress resistance mechanisms, a remarkable forging of life history theory (Rollo 1994) to molecular mechanisms.[6,14]
Rollo, C.D. 2002. Growth negatively impacts the life span of mammals. Evol. Develop. 4: 55-61.
(121 citations) Highlighted on Science’s “Science of Aging Knowledge” website and reviewed in Trends in Evolution and Ecology. The paper confirms a negative relationship between growth and lifespan in mice and rats. Results validated the transgenic growth hormone mouse as a model of elevated free radicals associated with enhanced growth and reduced longevity. Recent work, particularly with crickets,[2] reinforced growth rate as a critical determinant of aging. [2-5,14,15,17,18]
3. Evolutionary Biology: Papers 2, 6-9, 12-18
Rollo, C.D. 1994. Phenotypes: their Epigenetics, Ecology and Evolution. Chapman and Hall, London This peer-reviewed book synthesized a holistic evolutionary theory incorporating development, phenotypic plasticity and sexual reproduction. Life history theory pertaining to the Principle of Allocation (tradeoffs) and risk was extended to other fields, including gerontology. Insights from transgenic growth hormone mice (enforced allocation to enhanced growth) was elaborated, along with predictions regarding aging that were subsequently confirmed. The book was recognized in Nature, Trends in Evolution and Ecology, Trends in Genetics, and the J. of Animal Ecology as a founding contribution to the field of “Evolution and Development.” Recent favourable comments are found in the Quarterly Review of Biology, The Biologist, and BioScience. The book earned an editorial board invitation from the journal “Evolution and Development.” My theories have progressed to identify a general and highly conserved temporal framework spanning phenotypes to genes as well as specific pathways and tradeoffs central to growth, aging, stress resistance and adaptive plasticity.[2,6,8,9, 12-14]
2. RECENT CONTRIBUTIONS. Graduate students: Chaudhry, Lemon, Aksenov, Lyn, Matravadia, LeBlanc. Bracketed numbers = references for the grant proposal. Student names bolded. Corresponding author = “*”. All contributions were funded by NSERC.
Refereed Publications Published or Accepted
[1]
Aksenov V, Khanna P, Long J, Liu J, Szechtman H, Matravadia S, Rollo CD.* 2012. A complex dietary supplement improves spatial learning, increases brain size and improves mitochondrial activity in aging mice. AGE: DOI: 10.1007/s11357-011-9325-2 (Impact Factor (IF): 6.28) Supplemented mice expressed youthful learning at ages when untreated mice learned nothing.
[2] Lyn J, Aksenov V, LeBlanc Z, and Rollo CD.* 2012. Life history features and aging rates: Insights from intra-specific patterns in the cricket Acheta domesticus. Evol. Biol. 39: 371-387. (IF: 3.61) Growth and maturation modulate aging and life span was more than doubled via dietary interventions
[3] Long J, Aksenov V, Rollo CD, Liu J. 2012. A complex dietary supplement modulates nitrosative stress in normal mice and in a new mouse model of nitrosative stress and cognitive aging. Mech. Ageing Develop. 133: 523-529. (IF: 3.44) doi.org/10.1016/j.mad.2012.04.001 [4] Lyn, J., Naik, W., Aksenov, V., Rollo, C.D.* 2011. Development of the cricket Acheta domesticus as a model of aging. AGE 33:509-522. (IF: 6.28) DOI: 10.1007/s11357-010-9195-z [5]Aksenov, V., Long, J., Lokuge, S., Foster, J., Liu, J., Rollo, C.D.* 2010. A dietary intervention ameliorates age-related declines in locomotion, neurotransmitters and mitochondrial activity. Expt. Biol. Med. 235: 66-76. (IF: 2.95) This work resulted in a Plenary Speakership in China.
[6]Rollo, C.D. 2010. Aging and the mammalian regulatory triumvirate. Aging and Disease 1: 1(2): 105-138. (http://www.aginganddisease.org/A&;D-Rollo-final.pdf). One of two syntheses identifying the circadian regulatory structure associated with TOR, FOXO and sleep. Peer reviewed and invited by editors from the prestigious Buck Institute, a front running leader in aging research. [7]Yao, M., Rosenfeld, J., Attridge, S., Sidhu, S., Aksenov, V., Rollo, C.D.* 2009. The ancient chemistry of avoiding risks of predation and disease.Evol. Biol. 36:267-281. (IF:3.61) We identified signals of injury and death conserved in insects and crustaceans spanning >420 million years of phylogenetic distance. Death recognition and avoidance represent a unique paradigm and class of behaviour-modifying chemicals. See international coverage in “public awareness/education” below.
[8]Rollo, C.D. 2009. Dopamine and aging: Intersecting facets. Neurochem. Res. 34:601-629 (IF:2.24). Peer reviewed special Invitation. Provides a new unifying theory of regulatory evolution.
[9]Chaudhry, A., Marsh-Rollo, S., Aksenov, V.,
Rollo, C.D.,* Szechtman, H. 2008. Modifier selection by transgenes: The case of growth hormone transgenesis and hyperactive circling mice. Evol. Biol. 35:267-286. (IF: 3.61) Describes impacts of modifier genes on transgenic GH overexpression and an entirely new way to generate novel genotypes that are phenotypically opposite to genes of interest. [10]Lemon, J.,
Rollo, C.D., Boreham, D.R. 2008. Elevated DNA damage in a mouse model of oxidative stress: impacts of ionizing radiation and a protective dietary supplement.
Mutagenesis 23: 473-482. Supplement prevented radiation-induced DNA damage. (IF: 3.18) [11]Lemon, J.,
Rollo, C.D., McFarlane, N.M., Boreham, D.R. 2008. Radiation-induced apoptosis in mouse lymphocytes is modified by a complex dietary supplement: the effect of genotype and gender. Mutagenesis 23: 465-472. Supplement prevented radiation-induced apoptosis. (IF: 3.18) [12]Rollo, C.D. 2006. Radiation and the regulatory landscape of neo2-Darwinism. Mutation Res. 597: 18-31. (IF: 2.85) Elicited a Speakership in Nevada
Other Refereed Contributions
[13]Rollo, C.D. 2007. Multidisciplinary aspects of regulatory systems relevant to multiple stressors: aging, xenobiotics and radiation. In: C. Mothersill, I. Mosse and C. Seymour (Eds.). Multiple Stressors: A Challenge for the Future. Springer (NATO Science) 185-224. (Peer Reviewed Invited Submission).Describes a unified multidimensional global framework related to aging and stress resistance.
Non-Refereed Contributions
[14]Rollo, C.D. 2012. Circadian Redox Regulation. In: Pantopoulos, K, Schipper HM (Eds.) Principles of free radical biomedicine. New York: Nova Science Publ. pp 575-627. (Free download:
https://www.novapublishers.com/catalog/product_info.php?products_id=32659). An invited synthesis identifying circadian regulatory structure associated with redox, growth and stress resistance. [15]Rollo, C.D. 2007. Overview of Research on Giant Transgenic Mice with Emphasis on the Brain and Aging. In: T. Samaras (Ed.). Human Body Size and the Laws of Scaling. Nova Scientific Publishing : 235-260. Refereed by T. Samaras and A. Bartke [16]Rollo, C.D. 2007. Speculations on the Evolutionary Ecology of Homo sapiens with Special Reference to Body Size, Allometry and Survivorship. In: T. Samaras (Ed.). Human Body Size and the Laws of Scaling. Nova Scientific Publishing :261-300. Refereed by T. Samaras and A. Bartke [17]Rollo, C.D. 2007. The Evolutionary Ecology of Body Size with Special Reference to Allometry and Survivorship. In: T. Samaras (Ed.). Human Body Size and the Laws of Scaling. Nova Scientific Publishing: 213-234. Refereed by T. Samaras and A. Bartke [18]Rollo, C.D. 2007. Technical Review of Molecular and Physiological Aspects Relevant to Size, Free Radicals and Aging. In: T. Samaras (Ed.). Human Body Size and the Laws of Scaling. Nova Scientific Publishing: 341-357. Refereed by T. Samaras and A. Bartke
