A model of aging as accumulated damage matches observed mortality patterns and predicts the life-extending effects of prospective interventions

Phoenix, Chris; Grey, Aubrey D.N.J. de

doi:10.1007/s11357-007-9038-8

Cited by 14 publications

(9 citation statements)

References 8 publications

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“…DOI: 10.7554/eLife.02077.010 other hand, the increase in the number of detected metabolites clearly differed from general ageassociated changes, and its commonalities in the two dietary conditions exclude the role of exogenous compounds. The extended metabolome composition may include by-products that affect viability and damage forms that reach and pass the detection thresholds during organism's aging (Phoenix and de Grey, 2007), but they likely represent only the tip of the iceberg of cumulative damage. Further advances in instrumentation and sensitivity of metabolite profiling should expose additional metabolites that characterize cumulative damage.…”

Section: Discussionmentioning

confidence: 99%

Author response: Age- and diet-associated metabolome remodeling characterizes the aging process driven by damage accumulation

Avanesov

Pierce

et al. 2014

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Aging is thought to be associated with increased molecular damage, but representative markers vary across conditions and organisms, making it difficult to assess properties of cumulative damage throughout lifespan. We used nontargeted metabolite profiling to follow age-associated trajectories of >15,000 metabolites in Drosophila subjected to control and lifespan-extending diets. We find that aging is associated with increased metabolite diversity and low-abundance molecules, suggesting they include cumulative damage. Remarkably, the number of detected compounds leveled-off in late-life, and this pattern associated with survivorship. Fourteen percent of metabolites showed age-associated changes, which decelerated in late-life and long-lived flies. In contrast, known metabolites changed in abundance similarly to nontargeted metabolites and transcripts, but did not increase in diversity. Targeted profiling also revealed slower metabolism and accumulation of lifespan-limiting molecules. Thus, aging is characterized by gradual metabolome remodeling, and condition-and advanced age-associated deceleration of this remodeling is linked to mortality and molecular damage.

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Section: Discussionmentioning

confidence: 99%

Author response: Age- and diet-associated metabolome remodeling characterizes the aging process driven by damage accumulation

Avanesov

Pierce

et al. 2014

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“…This feature also implies simpler and more rapid clinical testing, because any effects will necessarily be more immediate and direct (23). Regenerative therapies are thus especially attractive because they have effects even when initiated late in life, when the body has already accumulated extensive age-related changes (23, 24). …”

Section: Research Roadmapmentioning

confidence: 99%

The Demographic and Biomedical Case for Late-Life Interventions in Aging

Rae¹,

et al. 2010

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The social and medical costs of the biological aging process are high and will rise rapidly in coming decades, creating an enormous challenge to societies worldwide. In recent decades, researchers have expanded their understanding of the underlying deleterious structural and physiological changes (aging damage) that underlie the progressive functional impairments, declining health, and rising mortality of aging humans and other organisms and have been able to intervene in the process in model organisms, even late in life. To preempt a global aging crisis, we advocate an ambitious global initiative to translate these findings into interventions for aging humans, using three complementary approaches to retard, arrest, and even reverse aging damage, extending and even restoring the period of youthful health and functionality of older people.

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“…3.4.3.4.6 The possibility of extending this life-span via age-reversal therapies is the subject of an article recommended to the scoping project by an expert in genetics. Phoenix & de Grey (2007) have introduced the concept of the 'longevity escape velocity'. This claims that ageing can be functionally defeated long before there are comprehensive age-reversal therapies, as each improvement buys time for beneficiaries which can be spent developing the next improvement.…”

Section: In 2005mentioning

confidence: 99%

Scoping Mortality Research: (Report of the Mortality Research Steering Group)

Macdonald¹

2009

Br. Actuar. J.

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The Actuarial Profession is currently undertaking a review of its research strategy, and has decided to focus more resources on researching mortality developments. It is important that the profession is involved in partnerships with researchers from outside of the profession, bringing actuarial expertise into closer contact with other disciplines. We believe that collaboration between these different areas of expertise will provide important new insights in understanding mortality trends. This report represents the first step by the Mortality Developments Scoping Project Steering Group to map current research into mortality developments across a wide range of disciplines. The steering group is aware that the themes and literature discussed in this report are not exhaustive; however it does include areas of research not normally covered by the Actuarial Profession. The steering group welcomes comments on the report and suggestions for any areas which may not yet have been covered.The main aim of this report is to provide an overview of the key areas of research into mortality developments across a wide range of disciplines, as well as areas of overlap and gaps in the research. The literature described is compiled from recommendations received by the Mortality Developments Scoping Project Steering Group from experts from different disciplines working in the area of mortality.Key themes identified from recommended literature:— the role of medicine in mortality reduction;— the role of lifestyle and environment in mortality reduction, including smoking, socio-economic conditions and obesity;— causes of death contributing to mortality reduction, in particular coronary heart disease;— mortality reduction attributable to differing age groups;— the relationship of active life expectancy to total gains in life expectancy;— evidence of cohort effects on mortality improvement; and— future trends in mortality developments.Areas of overlap identified from recommended literature are:— the overlap between literature examining the role of medicine in mortality decline and the influences on the decline in mortality from coronary heart disease; and— the areas of overlap between various disciplines working in the field of mortality developments.Gaps identified in recommended literature are:— a lack of recommendations from social policy;— few papers recommended on the role of lifestyle and behavioural factors on mortality;— few papers recommended on causes of death other than coronary heart disease; and— few papers recommended on potential threats to future mortality improvement.

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A model of aging as accumulated damage matches observed mortality patterns and predicts the life-extending effects of prospective interventions

Cited by 14 publications

References 8 publications

Author response: Age- and diet-associated metabolome remodeling characterizes the aging process driven by damage accumulation

Author response: Age- and diet-associated metabolome remodeling characterizes the aging process driven by damage accumulation

The Demographic and Biomedical Case for Late-Life Interventions in Aging

Scoping Mortality Research: (Report of the Mortality Research Steering Group)

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