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Time to talk SENS: critiquing the immutability of human aging
Aubrey D N J de Grey1, Bruce N Ames, Julie K Andersen
1Department of Genetics, University of Cambridge, Cambridge, UK. ag24@gen.cam.ac.uk
Abstract:
Aging is a three-stage process: metabolism, damage, and pathology. The biochemical processes that sustain life generate toxins as an intrinsic side effect. These toxins cause damage, of which a small proportion cannot be removed by any endogenous repair process and thus accumulates. This accumulating damage ultimately drives age-related degeneration. Interventions can be designed at all three stages. However, intervention in metabolism can only modestly postpone pathology, because production of toxins is so intrinsic a property of metabolic processes that greatly reducing that production would entail fundamental redesign of those processes. Similarly, intervention in pathology is a "losing battle" if the damage that drives it is accumulating unabated. By contrast, intervention to remove the accumulating damage would sever the link between metabolism and pathology, and so has the potential to postpone aging indefinitely. We survey the major categories of such damage and the ways in which, with current or foreseeable biotechnology, they could be reversed. Such ways exist in all cases, implying that indefinite postponement of aging--which we term "engineered negligible senescence"--may be within sight. Given the major demographic consequences if it came about, this possibility merits urgent debate.
Insights
Aging involves metabolism, damage, and pathology. Removing accumulated damage, not altering metabolism or pathology, offers the best strategy for indefinite life extension, termed engineered negligible senescence.
Area of Science:
- Biogerontology
- Biotechnology
- Cellular and Molecular Biology
Background:
- Aging is characterized by metabolism, damage accumulation, and subsequent pathology.
- Metabolic processes inherently produce toxins, leading to cellular damage.
- Accumulated, unrepaired damage is the primary driver of age-related decline.
Purpose of the Study:
- To explore interventions targeting the three stages of aging: metabolism, damage, and pathology.
- To identify strategies for reversing accumulated cellular damage.
- To assess the feasibility of achieving indefinite lifespan extension through damage removal.
Main Methods:
- Review of current and emerging biotechnologies for damage repair.
- Analysis of the aging process as a sequence of metabolism, damage, and pathology.
- Evaluation of intervention points within the aging cascade.
Main Results:
- Interventions in metabolism or pathology offer only modest or limited benefits.
- Damage accumulation is the critical bottleneck in aging.
- Biotechnological approaches exist to reverse major categories of age-related damage.
Conclusions:
- Reversing accumulated damage, rather than altering metabolism or pathology, can potentially halt aging.
- Engineered negligible senescence (indefinite postponement of aging) is a theoretically achievable goal.
- The profound demographic implications necessitate urgent discussion and research into aging interventions.