Search tips
Search criteria

Results 1-5 (5)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
Document Types
1.  How Much Should We Weigh for a Long and Healthy Life Span? The Need to Reconcile Caloric Restriction versus Longevity with Body Mass Index versus Mortality Data 
Total caloric restriction (CR) without malnutrition is a well-established experimental approach to extend life span in laboratory animals. Although CR in humans is capable of shifting several endocrinological parameters, it is not clear where the minimum inflection point of the U-shaped curve linking body mass index (BMI) with all-cause mortality lies. The exact trend of this curve, when used for planning preventive strategies for public health is of extreme importance. Normal BMI ranges from 18.5 to 24.9; many epidemiological studies show an inverse relationship between mortality and BMI inside the normal BMI range. Other studies show that the lowest mortality in the entire range of BMI is obtained in the overweight range (25–29.9). Reconciling the extension of life span in laboratory animals by experimental CR with the BMI–mortality curve of human epidemiology is not trivial. In fact, one interpretation is that the CR data are identifying a known: “excess fat is deleterious for health”; although a second interpretation may be that: “additional leanness from a normal body weight may add health and life span delaying the process of aging.” This short review hope to start a discussion aimed at finding the widest consensus on which weight range should be considered the “healthiest” for our species, contributing in this way to the picture of what is the correct life style for a long and healthy life span.
PMCID: PMC4115619  PMID: 25126085
longevity; life span; caloric restriction; dietary restriction; body weight; body mass index; mortality; obesity paradox
2.  Relationship of spindle assembly checkpoint fidelity to species body mass, lifespan, and developmental rate 
Aging (Albany NY)  2011;3(12):1206-1212.
We have examined the tolerance of the spindle assembly checkpoint (SAC), as measured by the appearance of tetraploid cells in the presence of a microtubule inhibitor, in a series of primary cell strains derived from species with diverse lifespan and body size. We find that the integrity of the SAC varies among these species. There is a robust correlation between the integrity of the SAC and body size, but poor correlation with longevity and parameters of species development (i.e., time of female fertility, gestation length, and postnatal growth rate). The results suggest that fidelity of the SAC co-evolved more closely with the number of mitoses needed to reach adulthood than with species lifespan.
PMCID: PMC3273901  PMID: 22201071
tetraploid; mitosis; fibroblasts; mouse; human; stability; genome; lifespan; aging
3.  53BP1 contributes to a robust genomic stability in human fibroblasts 
Aging (Albany NY)  2011;3(9):836-845.
Faithful repair of damaged DNA is a crucial process in maintaining cell viability and function. A multitude of factors and pathways guides this process and includes repair proteins and cell cycle checkpoint factors. Differences in the maintenance of genomic processes are one feature that may contribute to species-specific differences in lifespan. We predicted that 53BP1, a key transducer of the DNA damage response and cell cycle checkpoint control, is highly involved in maintaining genomic stability and may function differently in cells from different species. We demonstrate a difference in the levels and recruitment of 53BP1 in mouse and human cells following DNA damage. In addition, we show that unresolved DNA damage persists more in mouse cells than in human cells, as evidenced by increased numbers of micronuclei. The difference in micronuclei seems to be related to the levels of 53BP1 present in cells. Finally, we present evidence that unresolved DNA damage correlates with species lifespan. Taken together, these studies suggest a link between recruitment of 53BP1, resolution of DNA damage, and increased species lifespan.
PMCID: PMC3227449  PMID: 21931182
53BP1; micronuclei; fibroblasts; mouse; human; stability; genome
4.  Significant Correlation of Species Longevity with DNA Double Strand Break-Recognition but not with Telomere Length 
Mechanisms of ageing and development  2009;130(11-12):784-792.
The identification of the cellular mechanisms responsible for the wide differences in species lifespan remains one of the major unsolved problems of the biology of aging. We measured the capacity of nuclear protein to recognize DNA double strand breaks (DSB) and telomere length of skin fibroblasts derived from mammalian species that exhibit wide differences in longevity. Our results indicate DNA DSB recognition increases exponentially with longevity. Further, an analysis of the level of Ku80 protein in human, cow, and mouse suggests that Ku levels vary dramatically between species and these levels are strongly correlated with longevity. In contrast mean telomere length appears to decrease with increasing longevity of the species, although not significantly. These findings suggest that an enhanced ability to bind to DNA-ends may be important for longevity. A number of possible roles for increased levels of Ku and DNA-PKcs are discussed.
PMCID: PMC2799038  PMID: 19896964
Species life-span; DNA-end binding activity; telomere length; DNA double-strand break repair; Ku protein
5.  Long-Term IGF-I Exposure Decreases Autophagy and Cell Viability 
PLoS ONE  2010;5(9):e12592.
A reduction in IGF-I signaling has been found to increase lifespan in multiple organisms despite the fact that IGF-I is a trophic factor for many cell types and has been found to have protective effects against multiple forms of damage in acute settings. The increase in longevity seen in response to reduced IGF-I signaling suggests that there may be differences between the acute and chronic impact of IGF-I signaling. We have examined the possibility that long-term stimulation with IGF-I may have a negative impact at the cellular level using quiescent human fibroblasts. We find that fibroblast cells exposed to IGF-I for 14 days have reduced long-term viability as judged by colony forming assays, which is accompanied by an accumulation of senescent cells. In addition we observe an accumulation of cells with depolarized mitochondria and a reduction in autophagy in the long-term IGF-I treated cultures. An examination of mice with reduced IGF-I levels reveals evidence of enhanced autophagy and fibroblast cells derived from these mice have a larger mitochondrial mass relative to controls indicating that changes in mitochondrial turnover occurs in animals with reduced IGF-I. The results indicate that chronic IGF-I stimulation leads to mitochondrial dysfunction and reduced cell viability.
PMCID: PMC2935370  PMID: 20830296

Results 1-5 (5)