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B L Strehler

Publications and source records attributed to B L Strehler.

11 recordsLinked to original sources
PubMed1979

Loss of hybridizable ribosomal DNA from human post-mitotic tissues during aging: I. Age-dependent loss in human myocardium.

DNA obtained from 29 male humans at autopsy was hybridized in liquid phase with tritium-labelled 18 and 28S ribosomal RNA (rRNA) in order to determine whether a change in the dosage in rDNA, which codes for rRNA, occurs during human aging. The individuals ranged in age from 3 months to 76 years. It was found that the amount of rDNA hybridizable per 260 nm absorption unit by DNA decreases by about 0.5% per year with a regression coefficient of about -0.83. These findings confirm earlier ones from this laboratory and indicate either a loss of these key genes during aging of humans or decreased hybridizability due to some other factor or factors. In any event, this degree of loss or inactivation of genes involving an all protein synthesis would seem to impair function of post-mitotic cells in response to maximal stress to about the same degree that function is lost in various human organ systems during aging, as defined by Shock and others.

Adolescent↗
PubMed1979

Loss of hybridizable ribosomal DNA from human post-mitotic tissues during aging: II. Age-dependent loss in human cerebral cortex--hippocampal and somatosensory cortex comparison.

DNA was isolated from the hippocampal and from the somatosensory cortex of 13 humans (at autopsy). In both the cortex and hippocampus, the loss of ribosomal DNA (rDNA), as measured through hybridization in the liquid phase, approximates about 0.9% per year. The r value for somatosensory cortex was about -0.7 and that for the hippocampus was about -0.91. The correlation coefficient between the sets of two samples derived from the same individual (two different areas) in +0.945. These results are consistent with those reported concurrently for human myocardium and with earlier studies conducted with beagle dogs, in which only post-mitotic tissues (brain, heart and skeletal muscle) showed measurable decrements in these key genes. To the degree that the synthesis of new proteins is essential for sustained mental activity, these results are consistent with the observations that Nissl substance is more slowly replenished, following exhaustive work by motor cortical cells, and the fact that many older persons experience mental fatigue during continuous mental work at earlier times than do younger persons. The mechanism of loss is not certain, but may well be related to inadequacies in DNA repair systems, thereby allowing deletion of tandemly duplicated genes through cross-over "episome" formation, followed by degradation of the excised DNA segments. The ratio of loss of rDNA hybridizability in human and dogs in about 1 to 7, which approximates the relative ratios of their lifespans (reciprocals).

Adolescent↗
PubMed1979

Developmental restrictions on transcription: determinants of the developmental program and their role in aging.

A developing plant system, the soybean hypocotyl has been used to investigate early transcription events which restrict auxin induced cellular proliferation to the appropriate developmental stage. Auxin treatment of 4-day old seedlings resulted in an early (6 hour) activation of chromatin-bound RNA polymerase activity wihich approached 200% of control values by 18 hours. This occurred without a detectable alteration in chromatin template capacity (assayed with exogenous RNA polymerase) and resulted in the synthesis of "induced RNA transcripts" as determined in vitro by nearest neighbor analysis. In contrast, auxin treatment of unresponsive 8-day old seedlings did not alter the chromatin-bound RNA polymerase activity. Hormonal activation did, however, result in the exposure of "induced template" regions in chromatin which could only be transcribed in vitro if exogenous RNA polymerase was included in the transcription reaction. Isoelectric focusing of the endogenous chromatin-bound and soluble RNA polymerase enzymes from successive developmental stages revealed that the chromatin-bound enzymes at the 2-day stage were first released from the chromatin complex and could be recovered in the soluble pool (4-day stage). This was followed by a gradual disappearance of these subspecies (6-day stage) until only a limited ensemble of RNA polymerase subspecies remained bound to chromatin and free in the soluble pool (8-day stage). Similar analyses of both the bound and free enzymes at the 4 and 8-day stages following auxin treatment revealed that the 4-day soluble enzymes could be induced to rebind to the chromatin complex in a defined sequence after hormone treatment while those of the 8-day hypocotyl were unable to do so. These developmental events indicate that the select loss of certain RNA polymerase subspecies serves to restrict the hormone responsivness of this tissue to the early developmental stages. Such restrictions could thus commit the constituent hypocotyl cells to their terminal post-mitotic phase of development.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1979

Polygamy and the evolution of human longevity.

An alternative to previous explanations of the rapid increase in man's longevity and intelligence during the several million years of his recent evolution from pre-hominid, clearly shorter-lived and less intelligent, primate ancestors is presented. The general thesis is that a very greatly accelerated rate of incorporation of favorable genes or gene combinations can be achieved in surprisingly few generations among social animals provided that dominant males become the patriarchs of many descendents by virtue of their partial or complete monopoly on available females. The conclusion is that man probably differs from his ancesters of 0.5 to 5 million years ago by many thousands of genes (both structural and regulatory) rather than the dozens or few hundreds that have been postulated on the basis of more classical treatments of selection pressures, gene frequency changes and mutation rates. The concepts developed here formally apply only to two alternative alleles, rather than to groups of genes which segregate independently, or to characters determined by multiple alleles. The appropriate mathematical treatment of the latter real situation is not readily visualized; nor is account taken of the likelihood that different tribes of pre-humans developed different specializations via the above mechanisms which were then (later) combined into an emerging human stock through matings between members of different tribes. The very great variability both in longevity and in intelligence between different races of animals such as dogs, which have been the objects of deliberate genetic selection by humans for particular heritable traits, may parallel our own recent history, even though the selection mechanism (deliberate human selection vs. polygamous dominance) is quite different in the two cases. The onset of civilizations consisting of amalgums between smaller, previously competing tribes, together with the humanitarian responsibilities to each other we share as a species, ironically has probably arrested further evolution of human longevity (and perhaps of intelligence) in the modern world. Possibly even retrogressive changes are occurring, except in those rare sub-populations in which special social and cultural practices tend to favor selective perpetuation of characteristics which are usually viewed as beneficial.

Alleles↗
PubMed1979

Aging research: current and future.

The key events that lead to organismic senescence appear to occur in cells that have been genetically programmed to arrest their own proliferation. After arrest, a variety of subcellular events occur, among the more important of which are the accumulation of waste product pigments, an increase in the fraction of inactive enzymes, and (probably of central importance) the loss of key genes, specifically those that code for rRNA. An understanding of the senescence of the epidermis and dermis would almost certainly provide answers to related problems in those organ systems whose sudden or slow failure leads to individual death.

Aging↗
PubMed1978

Developmental transitions between chromatin-bound and soluble RNA polymerase subspecies in the soybean hypocotyl.

RNA polymerase enzymes isolated from soybean hypocotyl tissue during successive developmental stages (2-8 days old) have been fractionated by Sephadex column isoelectric focusing. Both the enzymes bound to chromatin and those enzymes free in the soluble phase were investigated during development with respect to their distribution within these two pools. All observed activites were classified according to their alpha-amanitin sensitivity and isoelectric points. Two Class I subspecies (Ia, Ib) and two Class III subspecies (IIIa, IIIb) were continually present bound to chromatin throughout the developmental sequences except the IIb form which was absent at the latest stage. However, a great multiplicity (9 total) of Class II activities (totally inhibited by alpha-amanitin) were observed to be bound to chromatin at the 2nd day stage. These forms were first released from the chromatin complex and recovered in a soluble pool (4th day stage). Subsequent hypocotyl development was accompanied by the gradual disappearance of these Class II subspecies from this pool (6th day) until only two soluble species and one chromatin-bound Class II activity remained (8th day). These observations indicate that the early development of this tissue is accompanied by a dramatic alteration in the conplexity of chromatin-bound RNA polymerase subspecies. Such events may in part determine the domain of RNA secies synthesized at successive developmental stages.

Chromatin↗
PubMed1978

Developmental restrictions on hormone modulated gene transcription. II. Hormone induced interactions of RNA polymerase with chromatin.

Chromatin-bound and soluble RNA polymerase subspecies have been isolated and fractionated by isoelectric focusing at various times (0, 6, 12 and 18 h) following auxin treatment of 4 day (responsive) and 8 day (unresponsive) soybean hypocotyls. Young 4 day seedlings displayed two well defined phases of auxin induced gene transcription. Phase I (6 h) evidenced the selective dissociation of many RNA polymerase subspecies from the chromatin complex which was accompanied by the retention of three class II enzymes. Phase II occurred after 12 h of treatment when the dissociated enzymes including some species which were soluble in the 0 h controls became re-associated with chromatin. These induced RNA polymerases may be responsible for the synthesis of auxin induced RNAs. In contrast, the unresponsive 8 day hypocotyl did not display two phases of auxin induction. Phase one, the dissociation of the chromatin bound enzymes, occurred at 12 h (compared to 6 h for the 4 day seedling) and was not followed by the later translocation of any soluble enzymes towards the chromatin complex. The results support earlier findings suggesting that the developmental "phasing out" of RNA polymerase subspecies limits the hormone induced growth response of this tissue and thus is regarded as an off switch for the transcription of such hormone controlled gene sequences.

2,4-Dichlorophenoxyacetic Acid↗