Re: The genetics of human longevity - A DOSE OF REALITY

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from that article:

A DOSE OF REALITY

Generalizing results from lower organisms, such as worms, to humans—“nematomorphizing” the aging process—may not be appropriate. Worms do not develop pneumonia, have myocardial infarctions, break their hips, or become demented; they do not even have lungs, coronary arteries, bones, or brains. Protein products that have similar functions at the cellular level in various animal phyla may have different effects at the level of the organism. In addition, there is certainly overlap among genetic pathways; for example, caloric restriction may cause oxidative damage that leads to telomere shortening, cellular senescence, and aging (147).

Moreover, the conditions under which longevity genes developed in humans and in other species are not those under which we now age. Genes that are associated with longevity in our current environment—in which deaths from predation, exposure, starvation, and many infectious diseases are uncommon—may differ from those associated with longevity in animals and earlier humans. Current causes of cellular stress may not resemble those of 20,000 years ago. The human diet now has a caloric excess, not a deficit. Atherosclerosis has become an important cause of mortality only within the past few generations. Access to shelter, nutrition, public health, primary and secondary prevention, and medical care may be changing the genetic makeup of the elderly from what it would have been earlier.

Despite these problems, the identification of longevity genes or gene pathways may enable the development of treatments that increase lifespan and improve health. The search is not for targets for gene-replacement therapy—too many cells would need to be repaired—but for targets amenable to nongenetic therapies, such as small molecules that activate or deactivate these genes or their protein products, thereby slowing the aging process and extending human lifespan.

[ ] The genetics of human longevity

FYI.

The genetics of human longevity.Browner WS - Am J Med - 1-DEC-2004; 117(11): 851-60From NIH/NLM MEDLINE

NLM Citation ID:15589490 (PubMed)

Comment:

Am J Med. 2004 Dec 1;117(11):882-3PubMed ID: 15589498

Full Source Title:American Journal of Medicine

Author Affiliation:California Pacific Medical Center Research Institute, San Francisco, California 94115, USA. warren@...

Authors:Browner WS; Kahn AJ; Ziv E; Reiner AP; Oshima J; Cawthon RM; Hsueh WC; Cummings SR

Abstract:Many of the genes that affect aging and longevity in model organisms, such as mice, fruit flies, and worms, have human homologs. This article reviews several genetic pathways that may extend lifespan through effects on aging, rather than through effects on diseases such as atherosclerosis or cancer. These include some of the genes involved in the regulation of DNA repair and nuclear structure, which cause the progeroid syndromes when mutated, as well as those that may affect telomere length, since shorter telomeres have been associated with shorter survival. Other potential longevity genes, such as sirtuins, are involved in regulating the response to cellular stress, including caloric restriction. The best-studied pathway involves insulin and insulin-like growth factor 1 signaling; mutations in homologs of these genes have extended lifespan up to sixfold in model organisms. Other potential candidates include mitochondrial DNA and the genes that regulate the inflammatory response. Despite the challenges in study design and analysis that face investigators in this area, the identification of genetic pathways that regulate longevity may suggest potential targets for therapy.

Regards

[Guest guest]

from that article:

A DOSE OF REALITY

Generalizing results from lower organisms, such as worms, to humans—“nematomorphizing” the aging process—may not be appropriate. Worms do not develop pneumonia, have myocardial infarctions, break their hips, or become demented; they do not even have lungs, coronary arteries, bones, or brains. Protein products that have similar functions at the cellular level in various animal phyla may have different effects at the level of the organism. In addition, there is certainly overlap among genetic pathways; for example, caloric restriction may cause oxidative damage that leads to telomere shortening, cellular senescence, and aging (147).

Moreover, the conditions under which longevity genes developed in humans and in other species are not those under which we now age. Genes that are associated with longevity in our current environment—in which deaths from predation, exposure, starvation, and many infectious diseases are uncommon—may differ from those associated with longevity in animals and earlier humans. Current causes of cellular stress may not resemble those of 20,000 years ago. The human diet now has a caloric excess, not a deficit. Atherosclerosis has become an important cause of mortality only within the past few generations. Access to shelter, nutrition, public health, primary and secondary prevention, and medical care may be changing the genetic makeup of the elderly from what it would have been earlier.

Despite these problems, the identification of longevity genes or gene pathways may enable the development of treatments that increase lifespan and improve health. The search is not for targets for gene-replacement therapy—too many cells would need to be repaired—but for targets amenable to nongenetic therapies, such as small molecules that activate or deactivate these genes or their protein products, thereby slowing the aging process and extending human lifespan.

[ ] The genetics of human longevity

FYI.

The genetics of human longevity.Browner WS - Am J Med - 1-DEC-2004; 117(11): 851-60From NIH/NLM MEDLINE

NLM Citation ID:15589490 (PubMed)

Comment:

Am J Med. 2004 Dec 1;117(11):882-3PubMed ID: 15589498

Full Source Title:American Journal of Medicine

Author Affiliation:California Pacific Medical Center Research Institute, San Francisco, California 94115, USA. warren@...

Authors:Browner WS; Kahn AJ; Ziv E; Reiner AP; Oshima J; Cawthon RM; Hsueh WC; Cummings SR

Abstract:Many of the genes that affect aging and longevity in model organisms, such as mice, fruit flies, and worms, have human homologs. This article reviews several genetic pathways that may extend lifespan through effects on aging, rather than through effects on diseases such as atherosclerosis or cancer. These include some of the genes involved in the regulation of DNA repair and nuclear structure, which cause the progeroid syndromes when mutated, as well as those that may affect telomere length, since shorter telomeres have been associated with shorter survival. Other potential longevity genes, such as sirtuins, are involved in regulating the response to cellular stress, including caloric restriction. The best-studied pathway involves insulin and insulin-like growth factor 1 signaling; mutations in homologs of these genes have extended lifespan up to sixfold in model organisms. Other potential candidates include mitochondrial DNA and the genes that regulate the inflammatory response. Despite the challenges in study design and analysis that face investigators in this area, the identification of genetic pathways that regulate longevity may suggest potential targets for therapy.

Regards