Biogerontology research in Israel.

Studies on biogerontology in Israel are reviewed in relation to the academic and medical research setup, as well as to a variety of gerontological bodies that contribute to promotion of the research. Studies on the biology of aging are outlined with a view also on the relevance and possible applications to medicine. The various topics encompass longevity-associated genes, effects of calorie restriction, including studies on the experimental model of the alpha-MUPA mutant mouse, as well as basic issues regarding the central nervous system and skeletal tissues.

What accounts for the wide variation in life span of genetically identical organisms reared in a constant environment?

Individual organisms show marked variability in life span, even when they are of the same genotype and are raised in a common environment protected from extrinsic hazards. This intrinsic variability of life span is thought to arise from the stochastic nature of the cellular and molecular mechanisms controlling development and ageing. In this article we review what is currently understood about the factors underlying the variability of life span and consider the implications for research that aims to improve the predictability of health in old age.

The voyage to healthy longevity: from experimental models to the ultimate goal.

Understanding mechanisms underlying longevity, and endeavor towards the specific goals of alleviating frailty in old age, require a comprehensive approach that considers the various theoretical and experimental approaches, as well as compiling the data on humans. This logistic has underlined the program of the conference, and is reflected in the present special issue. Considerable volume of data now point to distinct genes that are associated with exceptional longevity in humans, as reflected from the articles in this volume.

Tumor necrosis factor promotes human T-cell development in nonobese diabetic/severe combined immunodeficient mice.

A major problem after clinical hematopoietic stem cell transplantations is poor T-cell reconstitution. Studying the mechanisms underlying this concern is hampered, because experimental transplantation of human stem and progenitor cells into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice usually results in low T-lymphocyte reconstitution. Because tumor necrosis factor alpha (TNFalpha) has been proposed to play a role in T-lineage commitment and differentiation in vitro, we investigated its potential to augment human T-cell development in vivo.

Age related microsatellite instability in T cells from healthy individuals.

Many immune functions decline with age and may jeopardize the elderly, as illustrated, for example by the significantly higher mortality rate from influenza in old age. Although innate and humoral immunity are affected by aging, it is the T cell compartment, which manifests most alterations. The mechanisms behind these alterations are still unclear, and several explanations have been offered including thymic involution and Telomere attrition leading to cell senescence.

T cells and aging, January 2002 update.

Age-related changes in the immune system may contribute to morbidity and mortality due to decreased resistance to infection and, possibly, certain cancers in the aged. Many studies mostly performed in mice, rats and man but also including monkeys and dogs have established that age-associated immune decline is characterized by decreases in both humoral and cellular responses. The former may be largely a result of the latter, because observed changes both in the B cell germline-encoded repertoire and the age-associated decrease in somatic hypermutation of the B cell antigen receptors are now known to be critically affected by helper T cell aging.

Hematopoietic cells and replicative senescence.

Replicative senescence describes the finite cell replicative capacity in response to chronic proliferative stimulation. A key element in this process is the shortening of the telomeres, which to a major extent is caused by the lack of expression of telomerase. Whereas this situation has been well documented for a variety of somatic cell types, the question of whether stem cells "senesce" in the course of enforced chronic sequential divisions is as yet unresolved.