List of Figures, Tables and Boxes

Figures

Figure	Title	Chapter
I.1	Why age is the master risk factor: disease incidence across later life	Introduction
1.1	The Gompertz law of mortality and the logic of slowing ageing	1
1.2	Ageing as loss of cellular identity, and the rationale for reversal	1
3.1	Modular ageing: two molecular modules drifting at different rates	3
4.1	Senescent-cell burden across the lifespan, with and without intermittent senolysis	4
4.2	The hallmarks across a lifespan: an interactive review	4
5.1	Autophagic flux under grazing versus time-restricted eating	5
6.1	Gompertz survival under ad libitum feeding, a mimetic and dietary restriction	6
7.1	Kill versus silence: SASP intensity under no intervention, intermittent senolysis and continuous senomorphic suppression	7
8.1	The therapeutic window of partial reprogramming: biological age versus identity retention	8
9.1	Regenerative output across the lifespan: conventional versus senescence-resistant cell infusion	9
9.2	Donor-cell contribution to a complemented organ as a function of developmental mismatch	9
10.1	Why the endpoint decides the trial: participants required for a clinical versus a biomarker endpoint	10
11.1	Standardised effect sizes from selected human longevity-relevant trials, with the magnitude implied by popular framings	11
12.1	The two engines of the demographic transition: falling fertility and rising life expectancy, 1950–2100	12
12.2	Shifting versus steepening the survival curve, and the compression of morbidity	12
12.3	Old-age dependency ratio by region, 1950–2100	12
13.1	Three trajectories of the longevity dividend (illustrative)	13
13.2	Healthy life expectancy at birth by country, 2021	13
14.1	Four normative frameworks for assessing intervention in ageing	14
15.1	The enhancement space: departure from the species-typical norm against strength of evidence	15

Tables

Table	Title	Chapter
1.1	Classical theories of ageing, by the kind of explanation they offer	1
2.1	The twelve hallmarks of ageing, classified	2
2.2	Integration of hallmarks of ageing, strata of organismal organisation, and hallmarks of health	2
3.1	Principal changes in the ageing epigenome	3
4.1	The double-edged roles of cellular senescence	4
5.1	The four arms of the nutrient-sensing network	5
6.1	Variance in lifespan explained by dietary restriction versus genetic background	6
6.2	Caloric restriction mimetics and geroprotectors: targets and evidence	6
7.1	Classes of senolytic and the senescent-cell vulnerability each exploits	7
8.1	Approaches to cellular reprogramming for rejuvenation, by induction and risk	8
9.1	Two routes to a replacement organ: blastocyst complementation versus xenotransplantation	9
10.1	The landmark longevity trials and the honest scope of each	10
11.1	Three contemporary cases of overreach in longevity research	11
13.1	Projected health-financing gaps in five European countries to 2060 (PASH)	13
15.1	Converging (NBIC) interventions against ageing and cognitive decline, by evidential standing	15

Boxes (callouts)

A running index of In depth and Analogy boxes will be compiled here as chapters are drafted.

Analogy — the hire car (Chapter 1)
In depth — what is the epithelial–mesenchymal transition? (Chapter 1)
Analogy — the dashboard warning lights (Chapter 2)
In depth — why macroautophagy was promoted to its own hallmark (Chapter 2)
Analogy — the score and the performance (Chapter 3)
In depth — the antagonistic histone switches (Chapter 3)
Analogy — data corruption and the master copy (Chapter 3)
Analogy — the aglet (Chapter 4)
In depth — the senescence arrest machinery (Chapter 4)
Analogy — the accelerator and the brake (Chapter 5)
In depth — the three arms of the proteostasis network (Chapter 5)
Analogy — the night shift (Chapter 5)
Key concept — restriction works through the sensors, not the stomach (Chapter 6)
Analogy — switching fuel tanks (Chapter 6)
In depth — the Interventions Testing Program (Chapter 6)
Analogy — fasting in a pill (Chapter 6)
Caveat — the distance between a slowed clock and a longer life (Chapter 6)
Key concept — senolysis exploits an addiction, not a weakness (Chapter 7)
Analogy — weeding, not spraying (Chapter 7)
In depth — the senescent surfaceome and the promise of immune senolysis (Chapter 7)
Caveat — clearing a cell is not curing a disease (Chapter 7)
Key concept — age and identity are two dials, not one (Chapter 8)
In depth — the backup copy, and whether a clock is a body (Chapter 8)
Analogy — rewinding the tape, not erasing it (Chapter 8)
Caveat — the tumour shadow, and a clock is not a body (Chapter 8)
Key concept — stem-cell exhaustion is a verdict, not a mechanism (Chapter 9)
Analogy — the orchard, not the fruit bowl (Chapter 9)
In depth — what ‘senescence-resistant’ actually engineers (Chapter 9)
Caveat — a primate trial is not a clinic (Chapter 9)
Key concept — the paracrine principle (Chapter 9)
In depth — blastocyst complementation, step by step (Chapter 9)
Caveat — the embryonic-stage ceiling and the contamination risk (Chapter 9)
Key concept — the four tests of a biomarker of ageing (Chapter 10)
Analogy — the speedometer and the destination (Chapter 10)
In depth — why a hard endpoint needs an army (Chapter 10)
Caveat — an indication that is not a disease (Chapter 10)
Key concept — three signatures of a paradigm that will be revised (Chapter 11)
Analogy — the rehearsal and the performance (Chapter 11)
Key concept — shifting the curve versus steepening it (Chapter 12)
Analogy — the long dusk and the sudden night (Chapter 12)
Reading the dividend figures (Chapter 13)
Hype cycles compared (Chapter 13)
Analogy — the cathedral and the queue (Chapter 13)
A contextual reading of the line (Chapter 14)
Consent over a long horizon (Chapter 14)
What the boundary has done (Chapter 14)
Key concept — moderate and radical enhancement (Chapter 15)
Caveat — reading Heidegger after the Black Notebooks (Chapter 15)
In depth — the Makropulos problem (Chapter 15)
Caveat — a field-guide to longevity claims that outrun their evidence (Epilogue)